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Heartburn During Pregnancy: Symptoms And Treatments

In this post, we will discuss Heartburn during pregnancy, its causes, medications, lifestyle changes, when to see a physician, and more.

Introduction

If you are pregnant and get chest pain and acidity after a meal, then it is probably heartburn. This condition is common in the first and third trimesters. Acid Reflux or GERD may affect females once the uterus begins to expand. It may even happen when the stomach shifts away from its normal position due to foetus growth.

Why Do You Get Heartburn During Pregnancy?

When you eat food, it travels down a tube between the mouth and stomach. This is the esophagus. The tube runs in the lower esophageal (LES). It is a muscular valve and goes into the stomach. It is a regulator between the stomach and esophagus. Whenever you have food, the tube opens to let it pass.

Also, it stops the stomach from throwing back the acids up. This time, LES closes down. In case of acid reflux or heartburn, this tube relaxes. It is unable to stop the stomach acid from going up into the esophagus. This is the reason why a pregnant woman may experience burning and pain in the chest.

After a person conceives, several hormonal changes happen in the body. These can cause the esophagus and LES muscles to relax more than necessary. Also, it occurs more frequently than normal. This is why more acid may go up the tube. It is more frequent when the woman has a large meal or is lying down.

For instance, if you are pregnant, then the foetus also grows in the first and second trimesters. This results in the uterus expanding to adjust this growth. So, the stomach handles a lot of exertion. This is another reason why stomach acids may more frequently push up into the esophagus.

Acid reflux happens in people with or without pregnancy. But it is more common when the foetus is already growing in the body. After a few weeks of unprotected intercourse, you find any signs of heartburn, such as nausea, missed periods. Then it is time to take a pregnancy test.

Causes of Acid Reflux During Pregnancy

Why does pregnancy increase the occurrence of GERD (Gastroesophageal Reflux Disease)? It is because, in the first trimester, the esophagus muscles push the food into the stomach slowly compared to other times. Also, it takes longer for your stomach to digest the food and empty. The body thus receives more time for the foetus to absorb nutrients.

However, this can also cause acid reflux. In the third trimester of pregnancy, heartburn may happen more often. This is because the foetus growth pushes the stomach from its original position. But not every pregnant female needs to experience this symptom.

As everyone’s body is different, the intensity and signs of discomfort will also vary. Also, the cause for heartburn depends on factors such as diet, habits, physiology, and health condition after conceiving. If the symptoms worsen, then you must consult your doctor immediately.

Here are some of the common causes of Gastroesophageal Reflux Disease during pregnancy:

Slow Digestion

The slow digestion process triggers because of high progesterone. The stomach has the food contents for a longer time. This is the reason for the excessive formation of gas. Thus, pregnant females may encounter heartburn usually after taking meals. It is better to thus have frequent and smaller meals.

Larger meals may slow down digestion even more. So, the acid reflux may increase at a greater intensity. You can stick to fresh fruits, vegetables, non-acidic food items, and lean meat to reduce the troubles of acidity.

Hormones

The pregnancy hormone – progesterone is responsible for providing the womb with nutrition. It also helps the baby to develop in the uterus. But this hormone is also the cause of acid reflux. This chemical relaxes muscles. Its presence loosens the lower esophageal valve muscles.

Whenever you feed, the muscles open to let the food pass into the stomach. Then it usually shuts tightly. But progesterone production in pregnancy causes the muscles to de-tense. So, the LES does not close off properly. Also, its muscles do not remain that tight. So, they do not restrict the acid from going up from your abdomen.

The more the acid backflows from your stomach to the esophagus, the risk of GERD increases. In worse cases, the pushing up of acid can even affect the throat. So, you may encounter a lot of burning sensations in the stomach, chest, and mouth in severe situations.

Growth of Foetus

In the later stages of pregnancy, the uterus expands more to accommodate the growth of the baby. Thus, the uterus competes with other organs to get more space. The pressure that the uterus creates on expansion, affects the stomach. This leads to the spilling out of stomach acids.

It happens usually when your stomach has food in it. The stomach will squeeze for space as the uterus grows. Thus, heartburn is possible as the trimester advances. You can take medications to reduce these side effects. Have a word with your doctor about it.

Medicines to Treat GERD in Pregnancy

To cope with acid reflux symptoms, you can take over-the-counter antacids. The ones with magnesium or calcium magnesium are good to go with. Some of the options are Maalox, Rolaids, and Tums. In the last stage of pregnancy, however, you may have to avoid magnesium-based medicines.

This mineral can disrupt labor contractions. Your doctor may restrict the use of antacids containing aluminum, sodium, aluminum carbonate, and aluminum hydroxide. These can cause fluid to build up in tissues. Or, it may also result in constipation. Do not take pills consisting of aspirin.

It is best to consult your healthcare provider for a suitable medication for GERD. Some alternative treatments and lifestyle changes can also ease the problem.

Lifestyle Tips to Stop Heartburn During Pregnancy

One method may not work for all. So, for different individuals, different methods may work. Lifestyle habits have a huge role in bringing positive changes during pregnancy. These can also resolve acid reflux. It is also relatively safer than medicines for babies and mothers. Here are some of the lifestyle tips:

Maintain a balanced body weight

Do not take food and beverages that can increase the possibility of acid reflux

Some of the foods to avoid are fatty items, acidic and spicy foods, chocolate

Also, restrict intake of too many tomato-based items, citrus fruits, caffeine

Do not drink too many carbonated beverages

Chew sugarless gum after food. It neutralizes acid throw-up into the esophagus

Take your meals a few hours before going to bed

Chew your food properly and eat slowly

This will cause the food to break down adequately reducing the risk of heartburn

Stay upright for an hour or two after a meal

You can also go for a short walk after food to improve digestion

Drink a glass of milk or eat yogurt to beat down the signs of GERD

Stick to frequent and smaller meals

Do not drink water during meals

You can however drink water in between the intake of food

You may try relaxation techniques, yoga, acupuncture, progressive muscle relaxation

Even guided imagery can work for a few women

Avoid smoking cigarettes or use of recreational products

Sleep with wedges or pillows to keep your upper body elevated

Do not wear tight-fitting clothes, stick to comfortable clothing

Sleep on the left side to position the stomach higher from your esophagus

When to Consult a Doctor?

Acid reflux may interfere with sleep at night. But you may return to normalcy after the acid backflow eases. Even if you take antacids, the moment the effect wears off, the symptoms may return. Some of the signs are coughing, black stools, difficulty swallowing, weight loss, etc.

If these symptoms worsen, then you must seek your doctor’s help. Your physician may provide a diagnosis for GERD. This will require immediate treatment for the complications. It is necessary to do so to protect the esophagus from damage. Your healthcare provider may prescribe H2 blockers.

These medicines prohibit acid production. Another option is a proton pump inhibitor. It is for individuals who do not respond much to other forms of treatments during pregnancy for heartburn. If you experience side effects from these medicines, then reveal the same to your doctor. He/she will suggest another one that is safe for you and the baby.

Final Words

Acid Reflux can occur at any stage of pregnancy. Not all women suffer from it. But this may affect a few females. The signs and symptoms may vary from a person to another. For some, it can limit heartburn after food. But for others, it can extend for several hours and disturb sleep.

It can also interfere with daily schedules. The burning sensation in the stomach, throat, and chest can get serious. It has the potential to burn a hole in the food pipe or throat, leading to severe health issues. So, if the symptoms seem bothersome, do not delay meeting your doctor. It will help counterattack the problem with the right treatment.

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Cancer Drug Prices Continue to Rise

Rising drug prices is an issue that everyone from the President to both Houses of Congress (Democrats and Republicans), Wall Street, and Main Street can agree must be alleviated, and perhaps the most expensive drugs are those that treat cancer.  This reality is a combination of the severity of the disease and the nature of the drugs, which are generally biologic drugs characterized by structural complexity, production difficulties, and high cost of regulatory approval.  As reported in Genetic Engineering News, the trend of increasing drug prices continued in 2018 among most of the top ten highest selling cancer drugs currently on the market.

The basis for the information disclosed in GEN is a report from IQVIA™ Institute for Human Data Science entitled Global Oncology Drug Trends 2018, which showed that cancer treatment costs average over $150,000 on 2017 with total spend in the U.S. in these drugs of almost $50 billion (compared with a total of $60 billion for the rest of the world).  The situation may get even worse, with cancer drug prices expected to double again by 2022 in the U.S. and there being an equivalent percentage rise (10-13% annually) in the rest of the world.

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Why Do Pills Have Different Colors?

When we take the drug, we can clearly see that although most of the pills are white, there are many pills in other colors. Why do pills have so many different colors?

1. The color of the tablets is mostly the primary color of the drug. Their color depends on the concentration of the chemical substance in it. Berberine tablets are yellow, because its active ingredient is yellow. Other similar ones are blue anti-inflammatory gallbladder tablets, red dipyridamole tablets, and black medicinal carbon tablets.

2. Easy to distinguish. The shape and color of tablets and capsules are important markers for distinguishing among different drugs. Pills of different colors and shapes can be quickly distinguished when multiple drugs are taken.

3. There seems to be an implicit correlation between color and drug expectations based on drug color. Studies have found that red, yellow and orange drugs produce a more intense irritating effect, while blue and green produce a stronger tendency to calm.

In the face of different color drugs, patients are more preconceived to think that red and black drugs will be more potent, while white drugs will be weaker.

4. The choice of the pharmaceutical company. When choosing the appearance of a drug, there is no specific meaning or uniformity for color. Pharmaceutical companies will choose the most attractive color for their customers to color coated or capsule drugs.

5. Avoid deterioration. Pigments have more or less shading. Colorants and opacifies are often added to the capsule to prevent light from passing through, which stabilizes the ingredients in the contents and is beneficial for improving the stability of the light-sensitive active ingredient. The pigment on the sugar coating of the tablet can also act as a light-shielding effect to avoid deterioration of the drug.

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All Eyes on Pharma Reps: The Myths, The Pressure, The Rewards

“At the end of the day, when I think that somewhere in my territory there is a patient whose life has been improved because of a product I promote, I get a warm, fuzzy feeling and a deep sense of personal satisfaction.”

— Corey Nahman, CEO, I

Pharmaceutical companies impact just about every American’s life. Our country is home to approximately 67,000 pharmacies, and according to a Mayo Clinic study, seven out of ten people in the United States take at least one prescription drug. From testing to production to selling to prescription, a medical product’s journey is complex and involves countless professionals.

The most significant of these professionals? For drug companies that want to stay in business, the answer is easy: sales reps. A pharma rep’s job is demanding, intricate, and at times exhausting. It requires specialized training in pharmacology as well as comprehensive knowledge of subject matters as diverse as biology and sales techniques. Succeeding as a pharma rep also takes a great deal of perseverance – not only to get the job done, but also to withstand misconceptions and misguided stereotyping.

Challenges and myths

If you’ve ever seen a pharma company hosting a banquet-room lunch for doctors and formed the assumption that pharma sales can be bought, think again. The complex relationship between reps and doctors is often incorrectly regarded as a quid-pro-quo system that starts with drug companies providing free meals and paid speaking engagements to doctors in exchange for those doctors prescribing their products. While it’s true that a strategy’s at work here, it’s not designed to woo. It’s about time – which, as we know all too well, doctors have very little of.

Often, coffee or a meal is the only avenue for pharma reps to get in front of a doctor. Moreover, the overwhelming majority of doctors won’t promote a drug they don’t like or believe in. So what’s actually happening at these lunches? The real answer is that salespeople and doctors are coming together to build a partnership focused on determining the best therapy options for patients.

That may sound like a lofty goal for a salesperson, and it is. That’s due not only to the stress of the sales process itself, but also because attaining and retaining a position is no walk in the park.

Many pharma reps come to the job with a background in chemistry, biology, or premed. According to the Princeton Review, pharma companies commonly demand that their sales employees have an advanced degree in the medical field. During their initial years in the industry, they often take advanced courses in pharmacology to deepen their knowledge of their company’s product line. Doing so helps them convey complex scientific and medical concepts in accessible language.

Reps may also have to learn how to interpret data and statistics so as to gain an understanding of both public and private health issues. As a primary source of information for doctors, they have to be prepared to discuss various diseases and new clinical studies, stay up to date with the competition, and thoroughly explain the qualities that make their product better than the competition.

In short, every last one of them has to become a trusted member of the local medical community.

The intensity, the intellectual challenge, and the satisfaction of helping patients may be just what draws people to this career. “You cannot get discouraged doing a job like this,” says James Bowden, a pharmaceutical sales specialist. “After all, by filling the shoes of a pharmaceutical representative, you bring a great added value to a physician and his or her patients through the drug products that you promote. Do not let anyone else tell you otherwise. That is why I’m doing what I love the most, and that is helping people live longer, healthier, and an overall better quality of life.”

In the best of all worlds, pharma reps are driven by an innate passion for the profession, and they find jobs with companies that value their unique skills and ability to build long-lasting relationships with doctors. But we don’t live in an ideal world, which means that reps’ financial satisfaction is a vital consideration.

A pharma rep’s earnings are 20-30% commission-based – a far higher rate than you’ll find in other industries. But the market is highly competitive – so much so that a “pay for performance” cult has developed and begun to take hold across other sales verticals. Recent HBR research shows that the number of companies offering bonuses or other forms of pay based on performance increased by 6% between 2014 and 2016 alone.

That sounds like great news for pharma reps, right? All they need to do in order to earn financial rewards is hit quota on a regular basis.

Of course, that isn’t as easy as it sounds. With quotas often set at unachievable heights, pharma reps are flying on a wing and prayer. Less than half will succeed – which means the majority will fail.

As you might imagine, failure is not a great bedfellow for reps, who tend to thrive on success; failure leads to frustration and loss of interest in selling your product. If you’re in a leadership position, you can avert such a scenario by instituting business processes that ensure goals are challenging but achievable – present and future – even during periods of enormous change.

How? With the right technology, for one. Advanced technology enables accurate quota management, balanced territory design, and – most importantly – forward-thinking comp plans that tap into your people’s inner motivations.

Gamification, for instance, appeals to salespeople’s competitive spirit. Visibility into individual and team performance will also light a fire beneath them; it’s empowering for reps to have access to sales and call-planning insights that indicate which doctors or institutions are likely to be most receptive to their overtures. Proper visibility also helps reps decide which doctors and institutions would benefit from more visits – and which would not. Add on a bonus calculator, which should be included with any truly robust technology solution, and reps can capitalize on these insights by projecting how much they can increase their earnings. When reps feel inspired to maximize their compensation, the company is simultaneously rewarded with better bottom-line performance.

But technology is only as good as the people who implement and use it. That means it’s vital to bring in expert staff who know their way around the tech and can help you utilize it to its full potential. These experts can conduct ongoing analyses of processes, continually gain and share insight, and cement improvement and revenue growth as an integral part of your company culture.

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E-Learning for Pharma: Digital Transformation Requires In-house Talents

A sharp surge of innovations in the pharmaceutical industry has created an environment where new tools and models of work appear every day, making difficult pharma concepts even more confusing and complex.

Pharmaceutical companies are overgrown with different strategies, while behind the scenes, there is an arms race of various tools and systems.

However, the main ingredient to win this competition is people, of course. Thus, pharma does everything to grow their talented specialist, investing all in the most valuable assets.

Let’s talk about how eLearning has become the first choice in the education and training of pharma teams, medreps, managers and many other specialists who play a hand in pharma’s continuous growth.

Being in the spotlight during the last year, life sciences seem to be on an unprecedented rise, any minute ready for new breakthroughs in science. 86% of technology professionals think that the healthcare and pharmaceutical industries’ digital moment has arrived. Sure enough, it has arrived, but the one thing it requires is the talents.

Simple outsourcing of these talents is not enough – many understand it, and now opt to grow their own in-house specialists, primarily investing in their future.

We came across the survey where Deloitte asked pharma and medtech companies about the top 5 issues they think will have the greatest impact on their companies in the following year. 35% of them identified the competition and demand for talent as the major ones.

Nothing stands still. The global pandemic has provoked a rapid surge of digital initiatives in healthcare but on the other hand, it greatly disrupted workplace practices inside pharmaceutical companies. Managing, training, and onboarding remote teams during the global pandemic is quite a burden, of course. The 4th edition of the Salesforce report was investigating how global customer service professionals were adapting to the realities of work in a pandemic. It turned out that 39% of high performing companies were successfully organizing remote teams’ training to keep employees updated, a little less but still 19% and 11% of moderate performing and underperforming companies were also investing in remote training for the staff.

A competitive environment like this has forced companies to reconsider their workplace practices and looking for an alternative way to provide mandatory educational training. eLearning provides an opportunity to meet some of those training needs as well as many others.

eLearning solutions offer a better learning experience based on interactive technologies, such as audio, video, graphs, and animations, and allow to conduct mandatory training and share valuable knowledge with all members of the teams.

5 reasons to consider eLearning for pharma, 

A few reasons why eLearning has become a preferred mode of learning in the pharma industry come down to the various benefits it offers.

Excellent indicators, but these are mainly economic, and let’s see what the long-term benefits are.

1.     Keep the team updated & provide necessary training

Now practically all advanced pharma companies are mastering omnichannel. This approach has become an evolutionary link in the lifecycle of pharma’s digital transformations. But it is important to understand that the real evolution towards omnichannel takes place within.

When a global pharmaceutical company is about to master and scale the right tools correctly – the desired aim is hard to achieve. For example, when your company is deploying certain omnichannel marketing tools they may simply not be suitable for all pharma’s affiliates. In fact, desynchronization occurs at different stages.

Therefore, it is more convenient to master and learn how to use certain tools with the help of eLearning technologies that are proving a convenient learning environment that allows covering the entire team.

Together with the end-user, you can create your own learning plan, update it gradually with new tools, translate content across all channels, and share valuable knowledge both globally and locally.

2.     Get analytics and track the progress

Typically, eLearning program contains a progress tracker that allows tracking the success of each learner. On top of that, organizers can also provide weekly email feedback to keep track of where the student is in the program and what comes next.

The learning plan consists of thematic modules with chapters, new modules become available as the student progresses. This creates a clear picture of how many employees of the company have mastered the new technology or completed mandatory training and with what results.

3.     Standardised approach to learning

eLearning technology may save a lot of time and money for the company, as you will have a consistent, compliant plan at hand. A professional team may create content according to your recommendations, and the system will ensure fast delivery of content to learners across all channels. For example, when our team at Viseven creates content for our customers, the process is usually as follows: they provide an eLearning plan while we do the rest: create, design, localize, build a customer journey, and plan integrations.

4.     Personalized, interactive experiences

Finally, give yourself the first good reason why would you consider eLearning. The transfer of interactive knowledge contributes to better perception, memorization of the necessary information, as well as provides inspiration to learn more. This is especially applicable to life sciences, where huge volumes of information that is not the easiest to memorize, require proper structuring, bright design, and correct presentation.

5.     Better information retention

After all, many people use eLearning because it helps them remember and process the received information much better. Compared to static, interactive content increases the retention of your messaging by 79%. This is also facilitated by the fact that the learning process, as in the case of Viseven, can be organized not only around virtual training and quizzes but also around live training, creating an educational mix for better memorization of information.

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Pharmaceutical Contract Manufacturing: The Solution to Production of Complex Substances

The inherent expertise of CMOs and CDMOs is believed to be capable of enabling reduction in the time-to-market a product, significant cost-benefits, as well as access to larger production capacities and novel technologies.  It is worth mentioning that there has been substantial merger and acquisition activity in the pharmaceutical contract manufacturing market in the past few years, as players strive to become one stop shops, in order to cater to the diverse needs of pharmaceutical developers (ranging from early-stage development to commercial production). Considering the ongoing innovation in production technologies, evolving pipeline of small molecule products and the increasing demand for such drug candidates, we believe that the pharmaceutical contract manufacturing market is likely to witness positive growth in the coming years.

Close to 500 companies claim to offer contract manufacturing services to pharmaceutical companies across the globe

Majority of the contract manufacturing facilities are located in Asia-Pacific region, followed by Europe and North America.

The last five years have witnessed ample increase in the number of expansion initiatives undertaken by pharmaceutical CMOs to expand development and manufacturing operations.

Owing to the rising competition among pharmaceutical companies and pressing need to reduce drug development timelines, the pharmaceutical contract manufacturing market is anticipated to witness ample increase in the coming decade.

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Endo Pharmaceuticals – Not Your Typical Off-Label Settlement

This post relates to yet another off-label settlement between a pharmaceutical company and the federal government.  But some aspects of this recent settlement, coupled with other recent cases, might indicate noteworthy trends in how these cases are being resolved.  The defendants are Endo Health Solutions, and its subsidiary, Endo Pharmaceuticals Inc., based in Malvern, Pennsylvania.  The drug is Lidoderm, a prescription drug patch that FDA approved to treat pain associated with post-herpetic neuralgia, or PHN.  The government alleged that Endo marketed Lidoderm for general, non-PHN related pain indications, including lower back pain, diabetic neuropathy, and carpal tunnel syndrome.  The company’s global settlement included a civil payment of $171.9 million, a criminal fine of $20.8 million, and a Corporate Integrity Agreement governing the company’s ongoing practices.

Two U.S. Attorney’s Offices bifurcated the matter, with the civil investigation managed by the U.S. Attorney’s Office in Philadelphia, and the criminal investigation handled by the Northern District of New York.  Dealing with multiple U.S. Attorney’s Offices can be complicated, but we have seen improved cooperation between multiple offices in recent cases.

Endo managed to escape a corporate criminal charge by entering into a deferred prosecution agreement with the government.  In the DPA, the company admitted to certain criminal conduct, and agreed to pay a criminal fine and to impose enhanced compliance measures. The DPA will not be final until it is accepted by the court.

The government used asset forfeiture techniques to buttress the criminal penalty.  As part of the resolution, the parties agreed to settle an in rem action the government had brought against a $10 million wire transfer intended for Endo Pharmaceuticals.  It is unclear from the publicly available pleadings how the government traced the wire transfer, but suffice it to say that money transfers of this magnitude do not go unnoticed when a company is in the crosshairs of a criminal investigation.  The government argued that the money constituted proceeds from a violation of the FDC Act, and therefore was subject to asset forfeiture under 18 As part of the criminal plea, the parties agreed to forfeit the $10 million wire transfer, plus pay an additional $10 million monetary fine.  Asset forfeiture is a powerful tool for the government, and one law enforcement agencies particularly prefer because the money is earmarked to further fund their investigative efforts.

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Psoriasis and Depression: The Lesser-Known Impact of the Disease

Psoriasis is a chronic inflammatory disease of the skin that affects both the personal and social lives of the people it strikes. Psoriasis Awareness Month is an important time to discuss one of the lesser-known impacts of the disease.

“Many people are familiar with the physical appearance of psoriasis, but most are unaware of the severe psychological impact it has on the patient,” says VMS BioMarketing Clinical Nurse Educator Samara Ashley, who provides education and support to people with this condition within the biopharma industry. “The severity of psychological distress from psoriasis is higher than most people realize.”

While psoriasis lesions can be physically uncomfortable, fear of social rejection and stigmatization can cause even worse psychological distress. Due to the visibility of psoriasis, people may suffer from embarrassment accompanied by low self-esteem, anxiety, and depression. Psoriatic lesions can appear anywhere on the body, but they often appear in areas such as the scalp, face, and hands. This challenge often leads patients to socially isolate themselves and may impact all areas of their life.

In a study recently published in the journal Cureus, researchers at the California Institute of Behavioral Neurosciences and Psychology studied the link between psoriasis and depression and how they amplify each other. Researchers found that 9.7% of psoriasis patients “wished they were dead” at the time of the study, and 5.5% had suicidal ideation. The way patients see their psoriasis directly impacts the severity of mental distress; the worse patients view their own symptoms, the worse depression may get.

While people with psoriasis face these emotional challenges year-round, Ashley says the impact of the warm summer weather only works to further these issues. “Often, especially in the summer,” she says, “I hear from so many patients who are uncomfortable due to breakouts, flaking skin, or dry itchy areas. They often want to wear more comfortable clothes – tank tops, sun dresses, shorts – but feel embarrassed or uncomfortable due to questions they get or looks from people out in public.”

Among all dermatological diseases, people with psoriasis have the highest risk of developing depression, researchers said, and this can catch patients in a dangerous cycle. As the visible symptoms develop, they may get more depressed about their self-image. In the study, depressed patients were shown to be more likely to develop worse symptoms. As stress and depression increased, so did psoriasis flare-ups.

If psoriasis patients continue down a depressive path, they may become more detached from their prescribed therapy, researchers noted, and patients who are depressed are most non-compliant. “They might think that they would never get rid of the disease despite the treatment. Managing the psychosocial part of the illness, along with its physical aspect, would give better treatment outcomes,” they said.

“This is why education and support are key ingredients in managing the symptoms of psoriasis,” says Ashley. “Through better education for healthcare providers and more psychological support, patients can be empowered to fight their psoriasis while maintaining their mental health.”

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PDUFA VII is critical for future biopharmaceutical innovation and for patients

Today, the U.S. Food and Drug Administration (FDA or Agency) released its performance goals letter for the seventh installment of the Prescription Drug User Fee Act (PDUFA).

PDUFA was first enacted in 1992 as a bipartisan solution to the then long FDA regulatory review timelines for new drugs and biologics. To this end, PDUFA allows the Agency to collect fees from biopharmaceutical companies to augment Congressional appropriations to increase FDA’s staffing and other resources to speed and enhance review process to help ensure patients have timely access to life-saving treatments. The PDUFA program helps provide efficiency and predictability of regulatory review while supporting continued independent rigor by the science-based Agency.

The PDUFA program has been critical in supporting the FDA’s ability to fulfill its central mission – to help protect and advance the public health. Thanks in part to PDUFA, the U.S. now leads the world in delivering new medicines to patients, and the FDA’s human drug review program is the global gold standard for regulatory review and approval. Before PDUFA, it often took FDA more than two years to review new medicines. Now, the median review time for a new medicine is 10 months for standard applications and 8 months for priority review applications.

The PDUFA VII goals letter expands upon the most recent iteration of the user fee agreements which expire in September of 2022 with a renewed focus on strengthening review fundamentals, enhancing accountability and transparency and advancing innovation for patients.

Key areas of the PDUFA VII goals letter include:

Enhancing patient-centric drug review and safety monitoring: Advance the incorporation of patient-centric data, including patient preference information, in drug development and regulatory reviews and support the Agency’s reviewing, tracking and communicating of post-market safety information.

Strengthening scientific dialogue and advancing innovation: Expand opportunities for sponsors to obtain FDA’s regulatory feedback and clarity throughout the drug development process.

Supporting the next wave of advanced biological therapies: Strengthen the Agency’s staff capacity and capability to support the development and review of cell and gene therapies.

Modernizing regulatory evidence generation and drug development tools: Advance the use of real-world evidence in regulatory decision making, facilitate further use of complex adaptive and other novel clinical trial designs, and advance consistency and predictability around the use of modeling and simulations.

Advancing digital technologies and information technology (IT) infrastructure: Facilitate adoption of innovative digital health technologies and modernize FDA’s data and IT capacity and capabilities, including adoption of cloud-based technologies.

Enhancing innovation in manufacturing and product quality reviews: Facilitate the use of innovative manufacturing technologies for both products in development and those commercially available and incorporates best practices from COVID-19 lessons learned for the use of alternative tools to assess manufacturing facilities.

Enhancing FDA hiring, retention and financial management: Build upon PDUFA VI efforts to improve accountability and transparency and modernize financial and staff resource management.

In adapting to and meeting the challenges presented by the COVID-19 pandemic, FDA and the biopharmaceutical industry are utilizing novel approaches to clinical trials and facility inspections to support continued innovation and inform efficient regulatory decision-making. PDUFA VII includes commitments that advance COVID-19 lessons learned, such as increased use of digital technologies and alternative tools to assess manufacturing facilities.

The PDUFA VII agreement will have a lasting and meaningful impact on the biopharmaceutical industry’s ability to develop innovative, safe and effective medicines for patients in a timely manner.

The timely reauthorization of PDUFA will allow FDA and biopharmaceutical companies to build on the incredible strides made during the previous PDUFA cycle. New developments in medical and fundamental science – including immunotherapies and cell and gene therapies – hold the promise of treating debilitating diseases such as cancer, diabetes and many rare disorders. Fulfilling this promise depends on a modern regulatory framework that PDUFA facilitates and that can serve patients by providing timely, science-based regulatory decisions. It is critical that Congress reauthorizes PDUFA, and supports the independent work of FDA, before its expiration in September 2022.

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The Pharmacist’s Role in Managing Allergies

Pharmacists can help patients with allergies acquire the right oral antihistamines or decongestants, steroid or decongestant nasal sprays, and/or eye drops based on symptoms.

For many patients, allergy season can be a dreaded time of year. Seasonal allergies affect 10%-30% of Americans on a yearly basis and can cause a plethora of symptoms, ranging from sneezing, runny nose, and itchy, watering eyes to shortness of breath, wheezing, swelling, and rash.

Luckily for these patients, there are many effective treatment options for mild to severe allergies available both OTC and by prescription. In fact, there are so many available treatment options that patients may often need guidance to choose the best products for their symptoms, which is the primary place the pharmacist comes in. There are many places in a patient’s allergy treatment journey where a pharmacist can plan an important role.

To begin, pharmacists are often involved in the management of a patient’s allergies from the very start. Many patients will approach a pharmacist for guidance on making a self-diagnosis based on symptoms.

Because seasonal allergies may affect patients differently year-to-year and even day-to-day, sometimes identifying these symptoms can be nuanced and difficult. Similarly, allergy symptoms often mimic the symptoms of a common cold.

Patients with new seasonal allergies may believe at first that they are suffering from a virus, and though treatment options may overlap in some ways for colds and allergies, correctly identifying the ailment and starting the most appropriate regimen immediately will certainly allow patients to feel better much sooner.

For most of these patients, allergies can be treated completely with OTC medications, requiring no visit to a physician and no prescription. This places pharmacists in a unique and important position for getting allergy patients started on the correct OTC therapies for their symptoms as there are so many products to choose from.

Because pharmacists are the most accessible health care providers and likely the most knowledgeable regarding OTC products, our role here is quite clear. Pharmacists can help patients acquire the right oral antihistamines or decongestants, steroid or decongestant nasal sprays, and/or eye drops based on symptoms.

Pharmacists can also help direct patients to potentially useful and cost-saving combination products that will address the correct symptoms while not overmedicating. Helping patients new to seasonal allergies deal with their symptoms OTC is not the only place a pharmacist plays a significant role in helping patients manage this disease state.

For many patients, OTC treatments will not successfully resolve their symptoms, requiring them to seek further care from either a primary care provider or an allergy specialist. These patients will likely receive prescriptions for rescue and/or steroidal inhalers, oral steroids, or leukotriene inhibitors.

For these patients, a pharmacist can assist in a more traditional sense by alleviating any burdens associated with adjudicating and dispensing their prescription medications. This role can also be significant because many of these medications, especially the inhaler products, can be quite costly and may often require prior authorization. Additionally, first-time inhaler users will greatly benefit from counseling from a pharmacist regarding how to properly use an inhaler to get the most from the therapy.

The pharmacist’s role in seasonal allergy management does not stop here. Although most patients will be able to use simple OTC remedies or commonly prescribed pharmaceutical products to manage their allergies, an appreciable sector of allergy patients need more specialized medications to properly treat this disease state.

These patients will likely see a specialist and will require less commonly used treatment options, such as immunotherapy injections, sublingual immunotherapy products, or biological medications. Many of these rarer and newer-to-market therapies often fall under the umbrella of specialty medications.

A specialty pharmacist’s role here is equally as important as in the other more common treatment scenarios. Patients who require specialty medications often need more support than other patients because of the complex nature of the medications as well as the specialty pharmacy process.

Although most allergy specialists are likely familiar with the specialty prescription dispensing process, some may not be. Therefore, it may take significant pharmacist intervention to ensure the prescription arrives at an appropriate specialty pharmacy where it can be successfully billed and dispensed. This can take several days or attempts, depending on the situation and the patient’s insurance.

Specialty pharmacists play a very important role in ensuring allergy patients can afford their medications which are typically quite expensive but might be less expensive after an insurance intervention or manufacturer coupon or rebate. Additionally, these patients will need thorough education and counseling regarding their new medications, which often have unique administration and/or storage requirements as well as more significant adverse effects.

In summation, there is clearly a wide range in the type of support patients will need in managing their seasonal allergies. Luckily for these patients, pharmacists are skilled and able to assist from the start of the process with symptom recognition and diagnosis to making OTC recommendations to helping those with severe symptoms manage a complex situation, as well as in the many situations in between.

Similarly to many other disease states or conditions, the role of pharmacists is vital and ever present in helping the many Americans who fight seasonal allergies navigate and successfully treat their symptoms.

[medicswiththeo]

A New Antibody-Dependent Enhancement Hypothesis

Here’s another post that I will regret writing, but a great many people have asked me about a new preprint that brings up the possibility of antibody-dependent enhancement with the current vaccines and the Delta variant. To be frank, some of the people promoting this seem to be rooting for the virus, just so long as it humiliates their enemies and proves their own positions to be correct, but there are a lot of honestly worried people out there who are wondering what this paper means. So let’s look at it, with an eye to lessons for evaluating such papers in general.

The authors are building on another recent paper on neutralizing and non-neutralizing antibodies against the current Covid-19 virus. The preprint version of that one came out in February, and the final version went online in June. That work appears to be very solid, and represents a great deal of effort, so let’s discuss it for a bit before returning to the preprint above. In it, the authors isolated antibodies from human patients that target the receptor-binding domain and others that target the N-terminal domain. They found using in vitro assays that both neutralizing and non-neutralizing antibodies that bound to the NTD showed antibody-dependent enhancement in cell infection. This took place partly through a well-known ADE pathway involving the Fc-gamma receptor, which allows for infection of macrophages, and this was indeed the main mechanism seen with ADE of the earlier SARS virus. It should be noted, though, that these seem to use different subtypes of the Fc-gamma receptor, so they’re not completely identical. And there were other cellular ADE events that were Fc-receptor-independent, though a mechanism that has not yet been worked out.

But the Li et al. paper went on to demonstrate that this does not seem to happen in animal models for these SARS-CoV-2 antibodies. Indeed, antibodies that showed ADE in the cell culture models still protected primates from viral replication when they were challenged by the actual virus. Three of the 36 monkeys in the study had increased lung inflammation compared to controls, but still had decreased viral replication, which makes it likely not ADE but some sort of effect of antibody treatment that is not mediated by virus. None of the animals that got the highest doses of antibodies, for example, showed any of these effects.

And the authors note that if antibody treatment led to ADE in humans, then it would have been seen in the convalescent serum trials and in its clinical usage. But it was not. Convalescent serum was not very beneficial in the end, but it was definitely not harmful. The paper also points out that the vaccine trials and the use of the vaccines in clinical practice have led to no signs of ADE, either. So ADE in cells for SARS-CoV-2 does not seem to translate to animal models of infection, and nothing of the sort has so far been observed in the human population.

Perhaps that’s why I haven’t been sent so many copies of the Li et al. manuscript, but rather this new one. I think it’s the title as well, which is an eye-catcher: “Infection-enhancing anti-SARS-CoV-2 antibodies recognize both the original Wuhan/D614G strain and Delta variants. A potential risk for mass vaccination?” The authors build on the earlier paper and make comparisons to the protein sequence of the Delta variant. They believe that the antibodies identified in the Li et al. paper as causing ADE in cell assays cause the Delta variant NTD to be more tightly bound to the membrane of human cells through an interaction with cell-surface lipid rafts, and they speculate that the balance between neutralization and infection enhancement, while favorable for earlier strains of the coronavirus, is tipped the other way for the Delta variant. About that title, while we’re on it I’m not completely sure why they reference mass vaccination risks and not risks posed by previous infection by non-Delta strains, because I would have to think that the same concerns would apply.

This one is not a very long paper, and there’s a good reason for that – it contains no experimental data. The postulated binding enhancement via lipid rafts is completely a molecular modeling result, and has not been demonstrated in actual cells. Their computations are explained in more detail in another paper, where you can see that the authors believe that it’s the kinetics of the lipid-raft interaction that may drive transmissibility of various viral strains.

I have no comment on that per se, but I do have to note that modeling-only conclusions about large protein binding events have to be confirmed by experimental data before they can be taken seriously. There are a great number of things that look plausible in such simulations that do not translate to reality. To illustrate that, here is a paper from the same three authors, again completely based on molecular modeling, that goes into a detailed mechanistic explanation of how azithromycin and hydroxychloroquine work together as an effective therapy against the coronavirus. The azithromycin binds to the RBD, you see, while the HCQ is affecting the conformation down at the lipid-raft-binding part of the NTD. That latter interaction is the subject of this earlier paper. The problem is, these two drugs together are not actually an effective therapy for coronavirus infection, a fact that the earlier papers’ citations of the work of Didier Raoult cannot overcome. It is a detailed calculated hypothesis to explain something that does not, in fact, exist.

This is a constant danger with simulations. Readers who have not encountered much molecular modeling are often impressed by the graphics and tables that appear with such work, but if you’ve been involved with actual experimentation you’ve seen many, many examples of such hypotheses that turned out to be built on air. Confusing the graphics with reality is a constant danger for all of us.

And in my view, the Yahi et al. paper is not aligned with reality. They do work in a line about how “although the results obtained so far have been rather reassuring" with a reference to the Li et al. paper, but they should also refer to the massive amount of real-world evidence now available. We have hundreds of millions of people who have been vaccinated to produce antibodies against the non-Delta coronavirus protein domains and are who are now being exposed to the Delta variant. To reiterate, there is no evidence whatsoever of ADE in this situation. In fact, we see the opposite: people who have been vaccinated are far less likely to become infected with the Delta variant, and if they become infected, they are far less likely to experience severe disease. These trends have been seen over and over in different populations, and they are the exact opposite of what you would see if ADE were operating. If the mechanism proposed by Yahi et al. were happening in the real world, then we should see higher Delta infection rates among vaccinated people, with more severe disease. We are not. We are seeing the reverse. The vaccines simply to not appear to be causing ADE, no matter how many reasons one might be able to spin for them to do so.

In short, get real.

[medicswiththeo]

The European coalition for vaccination calls on healthcare professionals to get vaccinated against COVID-19

In February 2021, the Coalition for Vaccination has published a manifesto to encourage healthcare professionals to get vaccinated against COVID-19.

The manifesto highlights three key reasons why all healthcare professionals should get vaccinated against COVID-19 when they have the opportunity to do so and why they should help promote the vaccination against COVID-19 among the general public.

You protect yourself from illness and possible severe or life-threatening complications

COVID-19 vaccines are safe and effective

You help safeguard healthcare capacity

The Coalition for Vaccination brings together European associations of healthcare professionals and relevant students’ associations in the field, as well as associated professional organizations working in the field of public health and immunization. It was convened by the European Commission in 2019 to deliver accurate information to the public, to combat myths and to exchange best practices. The Coalition is co-led by the Standing Committee of European Doctors, the European Federation of Nurses Associations and the Pharmaceutical Group of the European Union.

Updates from the European Medicines Agency

The European Medicines Agency published a direct to healthcare professional communication for Vaxzevria (previously Covid-19 Vaccine AstraZeneca), a plain-language description of medical terms related to medicines use and communications advising against the use of ivermectin for the prevention or treatment of Covid-19 outside randomized clinical trials and on the precautionary marketing suspension of the thalassemia medicine Zynteglo.

EMA has released a direct healthcare professional communication (DHPC) on the risk of thrombocytopenia and coagulation disorders with the COVID-19 Vaccine AstraZeneca. It contains important information for healthcare professionals prescribing, dispensing or administering this vaccine. As noted in the DHPC:

Benefits of the COVID-19 Vaccine AstraZeneca outweigh the risks despite the possible link to very rare blood clots with low blood platelets.

A combination of thrombosis and thrombocytopenia, in some cases accompanied by bleeding, has been observed very rarely following vaccination with COVID-19 Vaccine AstraZeneca.

Healthcare professionals should be alert to the signs and symptoms of thromboembolism and or thrombocytopenia.

Those vaccinated should be instructed to seek immediate medical attention if they develop symptoms such as shortness of breath, chest pain, leg swelling, persistent abdominal pain following vaccination. Additionally, anyone with neurological symptoms including severe or persistent headaches and blurred vision after vaccination, or who experiences skin bruising beyond the site of vaccination after a few days, should seek prompt medical attention.

EMA has created a medical terms simplifier that provides public-friendly descriptions of medical terms used for side effects of medicines and mechanisms of action. The 'EMA medical terms simplifier' has been assembled over many years by EMA’s medical writers, who use these plain-language descriptions to prepare public-friendly communications. Having become increasingly aware that there was no single resource for describing common medical terms found in medicines information, the team worked to produce a public-domain version of this resource.

Please note that the medical terms simplifier does not cover rarely used terms, most disease states, very specialized areas or the broader field of medical science. EMA will continue to maintain and further develop this resource over time.

EMA has reviewed the latest evidence on the use of ivermectin for the prevention and treatment of COVID-19 and concluded that the available data do not support its use for COVID-19 outside well-designed clinical trials.

In the EU, ivermectin tablets are approved for treating some parasitic worm infestations while ivermectin skin preparations are approved for treating skin conditions such as rosacea. Ivermectin is also authorized for veterinary use for a wide range of animal species for internal and external parasites.

Ivermectin medicines are not authorized for use in COVID-19 in the EU, and EMA has not received any application for such use. 

Following recent media reports and publications on the use of ivermectin, EMA reviewed the latest published evidence from laboratory studies, observational studies, clinical trials and meta-analyses. Laboratory studies found that ivermectin could block replication of SARS-CoV-2 (the virus that causes COVID-19), but at much higher ivermectin concentrations than those achieved with the currently authorized doses. Results from clinical studies were varied, with some studies showing no benefit and others reporting a potential benefit. Most studies EMA reviewed were small and had additional limitations, including different dosing regimens and use of concomitant medications. EMA therefore concluded that the currently available evidence is not sufficient to support the use of ivermectin in COVID-19 outside clinical trials.

Although ivermectin is generally well tolerated at doses authorized for other indications, side effects could increase with the much higher doses that would be needed to obtain concentrations of ivermectin in the lungs that are effective against the virus. Toxicity when ivermectin is used at higher than approved doses therefore cannot be excluded.

EMA therefore concluded that use of ivermectin for prevention or treatment of COVID-19 cannot currently be recommended outside controlled clinical trials. Further well-designed, randomized studies are needed to draw conclusions as to whether the product is effective and safe in the prevention and treatment of COVID-19.

This EMA public health statement has been endorsed by the COVID-19 EMA pandemic Task Force (COVID-ETF), in light of the ongoing discussions on the use of ivermectin in the prevention and treatment of COVID-19.

The company that markets the gene therapy medicine Zynteglo for treating the rare blood condition beta thalassemia has suspended sales pending investigation of a safety concern. The company, bluebird bio, notified EMA that a related medicine it was developing, which uses the same technology as Zynteglo, may have been associated with a case of cancer. Although no cases of cancer have been reported with Zynteglo itself, the company suspended marketing of Zynteglo until the possibility that the same risk might apply to the licensed medicine has been investigated.

The concern arose with the medicine, bb1111, intended to treat another blood disorder, sickle cell disease. This medicine uses the same viral vector as Zynteglo, based on a type of virus known as a lentivirus, to insert a working gene into the patient’s blood cells. One patient treated with bb1111 developed acute myeloid leukemia, a cancer of the blood, that might have been related to treatment, and a different blood disorder, myelodysplastic syndrome, was reported in another patient.

Cancer caused by this type of treatment (insertional oncogenesis) was already identified as a potential risk with Zynteglo, so patients who receive the medicine are followed up and monitored in a registry. So far no cases of cancer have been reported with Zynteglo treatment. Nonetheless, since bb1111 works in the same way, it was thought prudent to suspend clinical studies with bb1111 and pause sales of Zynteglo while the evidence is examined more thoroughly.

EMA is liaising closely with the company and experts within the regulatory network, and will now examine the evidence at EU level and decide on any relevant regulatory action for Zynteglo or any similar medicines under evaluation. No other authorized medicines use the same viral vector so no direct implications are foreseen for other licensed medicines.

Zynteglo was granted conditional marketing authorization on 29 May 2019. Currently it is only marketed in Germany, and because of limited availability and the rarity of the condition it is intended to treat, only a very small number of patients have received or would have been eligible to receive treatment. However, if treated patients do have any concerns they should contact the specialist supervising their Zynteglo treatment. EMA will communicate further once additional information becomes available.

[medicswiththeo]

F.D.A. Fully Approves Pfizer-BioNTech’s Vaccine, a First for a Covid-19 Shot

The Food and Drug Administration on Monday granted full approval to Pfizer-BioNTech’s coronavirus vaccine for people 16 and older, a decision that is likely to set off a cascade of vaccine requirements by hospitals, colleges and universities, corporations and other organizations.

Within hours, the Pentagon, CVS, the State University of New York system and the New York City school system, among others, announced that they would enforce mandates they had prepared but made contingent on the F.D.A.’s action.

The approval came as the nation’s fight against the pandemic has intensified again, with the highly infectious Delta variant biting deeply into the progress that the country had made over the first half of the year. The Biden administration hopes the development will motivate at least some of the roughly 85 million Americans who are eligible for shots but have so far rejected them to change their minds.

The regulatory move goes a step beyond the emergency use authorization that the agency granted in December. More than 92 million people have already been fully vaccinated since then with Pfizer doses. Some who have rejected the vaccines, expressing fears that they are experimental, have said they wanted to wait until the agency spent more time studying their safety and fully approved them.

In a roughly 10-minute address on the approval, President Biden said it should sweep away any lingering doubts about vaccines and spur more mandates. Appealing to corporate, state and local leaders, he said: “Do what I did last month. Require your employees to get vaccinated or face strict requirements.” In late July, he announced that all federal employees and on-site contractors must be vaccinated against the coronavirus or be required to submit to regular testing and other measures.

Mr. Biden tried to cast the F.D.A. approval as an example of how his administration was making headway against the pandemic, despite overflowing intensive care units in some states and an average of more than 1,000 lives a day lost. He said the death toll, while rising, was still far lower than it was last winter, because more than nine in ten older Americans are now vaccinated.

With the F.D.A. yet to authorize a vaccine even on an emergency basis for children younger than 12, Mr. Biden also tried to reassure anxious parents about the growing number of children who are getting infected with the Delta variant, saying that severe Covid-19 cases in that age group are still “very, very rare.” He also promised to soon address “how we get our kids back to school safely.”

The F.D.A., which has been under pressure to speed up its evaluations of coronavirus vaccines, gave full approval to Pfizer’s just 97 days after the company submitted the last of what regulators said were hundreds of thousands of documents. Officials said they were able to decide the matter in less than half the usual time because regulators worked nights and weekends and added staff members, not because they cut corners.

“This is a pivotal moment for our country in the fight against the pandemic,” Dr. Janet Woodcock, the acting F.D.A. commissioner, told reporters. “The public can be confident that this vaccine meets the F.D.A.’s gold standard for safety, effectiveness, and manufacturing quality that we require for an approved product.”

Some health experts are worried that the approval will unleash a wave of demands from vaccine recipients who want their doctors to prescribe booster doses. The federal government plans to begin rolling out third shots to people who had their second shot eight months earlier, but only after the F.D.A. clears extra doses and not until September 20.

“I think we just have to keep people calm,” said Dr. Jesse L. Goodman, a former chief scientist at the F.D.A. and now a medical professor at Georgetown University. He noted that more than one million Americans had already managed to get extra shots on their own and that demand could be difficult to control.

Ordinarily, final approval could give doctors a certain measure of freedom to prescribe a drug differently than the label advises. Pfizer is also ostensibly now free to market the vaccine, under the brand name Comirnaty.

In this case, though, as both Pfizer and the F.D.A. noted, the federal government controls the distribution of the vaccine in the United States. Dr. Woodcock strongly discouraged people from seeking a third shot until the F.D.A. has ruled on whether extra shots are safe and effective for the general adult population.

She specifically warned against giving the vaccine to children under 12, saying that doing so would be “of great concern” because regulators have not collected enough data yet from clinical trials on safety or the proper dose. Trials are still in progress for that age group, and a regulatory decision about emergency use could be several months away.

“We certainly want to make sure that we get it right in the children ages 5 through 11,” said Dr. Peter Marks, the F.D.A.’s top vaccine regulator, “and then even in younger children after that.”

The vaccine is still authorized for emergency use, instead of fully approved, for children 12 to 15.

Pfizer said it presented the F.D.A. with data from 44,000 clinical trial participants — half of whom got the vaccine, the other half a placebo — in the United States, the European Union, Turkey, South Africa and South America. The F.D.A. said the data showed the vaccine was 91 percent effective in preventing disease. That was a slight drop from the 95 percent efficacy rate in December, when the vaccine was cleared for emergency use. Pfizer said the decrease reflected the fact that researchers had more time to catch people who became sick.

Some public health experts were hopeful that the decision could push some of those hesitant about getting vaccinated off the fence.

Even if only 5 percent more Americans were persuaded to get shots, as some experts have predicted, “that’s still a huge slice of people,” said Dr. Thomas Dobbs, the chief health officer for Mississippi. Like a number of other Southern states, his has been ravaged by the Delta variant. He said licensure would help “shake loose this false assertion that the vaccines are an ‘experimental’ thing.”

A recent poll by the Kaiser Family Foundation, which has been tracking public attitudes during the pandemic, found that three of every 10 unvaccinated people said they would be more likely to get vaccinated with a shot that had been fully approved. But the pollsters and other experts warned that far fewer Americans might actually be swayed by the approval.

“I think that is a vanishingly small number of people in real life” who would change their minds because of the vaccine’s regulatory status, said Alison Buttenheim, an associate professor of nursing at the University of Pennsylvania and an expert on vaccine hesitancy. But if full approval spurs more requirements from employers and other organizations, she said, the results could be more significant.

“We still have a lot of people who just haven’t gotten around to it or don’t have huge objections, but no one’s told them they have to” get vaccinated, she said. “Mandates simplify things for people.”

Already on Monday, the Pentagon announced that the country’s 1.4 million active-duty troops would have to be vaccinated, and Gov. Philip D. Murphy of New Jersey said that all teachers in that state would have to get shots or submit to weekly testing. Chevron and CVS both said they would require some of their employees to receive coronavirus vaccines, and the State University of New York and the University of Minnesota systems announced similar requirements for students.

Wall Street rose, with investors buoyed by the vaccine news. The S&P 500 stock index was up almost 1 percent, and shares of Pfizer climbed 2.5 percent.

“The full regulatory approval of the Pfizer vaccine created hopes that it may spur additional gains in vaccination rates in the U.S., which would be an economic positive going forward,” said John Canavan, the lead analyst at Oxford Economics.

So far, 54 percent of Americans who have been fully inoculated have gotten Pfizer shots. Most of the rest received Moderna’s vaccine, which also requires two doses.

Dr. Marks said that federal health agencies would continue to monitor the Pfizer vaccine’s safety. The F.D.A. will also require Pfizer to continue to study the risk of myocarditis, an inflammation of the heart muscle, and pericarditis, an inflammation of the membrane surrounding the heart, in people who get its shot, including long-term outcomes for those who fall ill after vaccination. The F.D.A. in June attached warnings to the Pfizer and Moderna vaccines noting possible increased risk of both conditions after the second dose.

Less than two months after it appeared to have curbed the spread of the virus, the United States is averaging around 150,000 new cases a day and more than 90,000 hospitalized Covid-19 patients. Exactly two months ago, before the Delta variant fully took hold, federal health experts said the nation would be highly unlikely to again face a death toll of 1,000 or more people a day. The seven-day average as of Sunday was 1,008 daily deaths, according to a New York Times database.

“Full approval could not come at a more important time,” said Dr. Richard Besser, the president of the Robert Wood Johnson Foundation and a former acting director of the Centers for Disease Control and Prevention. He called on schools and businesses to require vaccination before allowing people to congregate indoors.

Vaccination rates have been rising steadily in recent weeks as fear of the Delta variant has grown. Providers were administering about 837,000 shots a day late last week, and Mr. Biden said the most recent seven-day total was the highest since early July. He said more people in Alabama, Arkansas, Louisiana and Mississippi — some of the states with the highest caseloads — got their first shots in the past month than in the previous two months combined.

Dr. Marks said that myths about the vaccines remain a major impediment to fighting the pandemic, including false claims that shots would cause infertility, would foster rather than prevent Covid-19, and had even led to thousands of deaths.

“Let me be clear: These claims are simply not true,” he said.

The F.D.A. is in the midst of a blizzard of decisions about coronavirus vaccines. The next major one looming is whether to authorize booster shots.

The Biden administration said last week it planned to offer third shots to adults who got the Pfizer and Moderna vaccines, eight months after their second injection, starting Sept. 20. Third shots are already authorized for some people with immune deficiencies, but the risk-benefit calculus is different for the general population.

Federal health officials said that both Pfizer’s and Moderna’s vaccines, which rely on similar technology, wane in potency over time. That trend, they said, is converging with the rise of the particularly dangerous Delta variant, making those who completed their vaccinations at the start of the year increasingly vulnerable to infection.

Some public health experts have challenged the plan for booster shots as premature. They say the available data shows that the vaccines are holding up well against severe disease and hospitalization, including against the Delta variant. Extra shots would be warranted only if the vaccines failed to meet that standard, some have said.

Regulators are still reviewing Moderna’s application for full approval of its vaccine, which it filed in June, a month after Pfizer. That decision could take several weeks. Johnson & Johnson is expected to apply for full approval soon.

[medicswiththeo]

Global Dose: Focus on Switzerland

One could say that the desire to find consensus among diverse groups is built into the framework of Switzerland.

The Swiss Confederation is comprised of 26 member states, called cantons, which can vary significantly in geography, culture and even language. Prior to the establishment of the Swiss federal state in 1848, cantons existed as fully sovereign states, with their own armies, border controls and currencies.

The quest for consensus between different groups is further facilitated by Switzerland’s unique political system. The Swiss executive body is composed of seven Federal Council members from different political parties, all with the same rights and powers. Referred to as a concordance system, decisions are made through negotiation and compromise.

This mindset has also permeated the country’s pharma industry. The Swiss pharma industry is harmonized across the entire value chain, with robust representation in active pharmaceutical ingredients, clinical research, drug development, manufacturing and contract services.

With a population less than the city of London, Switzerland is known for consistently “punching above its weight class,” with its multifarious, well-networked pharma industry. The industry is considered a pillar of the Swiss economy, accounting for 5.4% of the country’s gross domestic product and over 40% of Swiss exports.

Much of this success, according to Michael Altorfer, CEO of the Swiss Biotech Association a non-profit, member-driven organization representing the Swiss biotech industry can be attributed to the stability and balance that has been built into the infrastructure of the industry over the course of its long history.

“Switzerland is so broadly and strongly established that there is no field where you would not find activity. There has been decades-long investment into infrastructure on all levels, from education to research development, to hospitals, to manufacturing capacity,” Altorfer says. “The attitude of Switzerland is really reflected in the pharma industry.”

But for the past three decades, a key piece of this well-oiled Swiss pharma machine has been R&D startups and biotech small and medium-sized enterprises, which have thrived in the Swiss international collaboration model. Now, as countries around the world push for more nationalized approaches to supply chains, the Swiss pharma industry’s major source of innovation could come under fire.

[medicswiththeo]

How Key Companies Are Shaping The Bleeding Disorders Therapeutics Market?

Bleeding disorders, also known as coagulopathy, are a group of conditions in which the blood cannot clot properly due to the missing or defective protein. Bleeding Disorder can affect a person irrespective of his genders, ages and race and the person is likely to bleed more than the average person. A minor cut or scrape may result in intense bleeding.

The coagulation factors are proteins in the blood that works with platelets and plays a vital role in the blood clot. Platelets, bound together to form the fibrin clot, and any defect in the clotting factors or platelets can lead to excessive or prolonged bleeding. Excessive bleeding during or after surgery and injury, nosebleeds, bleeding of the gums, bleeding into joints, heavy menstrual bleeding are common symptoms of bleeding disorders. It is observed that most Bleeding disorders are inherited. Still, some of the diseases may develop over time due to certain medical conditions such as deficiency of vitamin K, medications side effects, low red blood cell count, and specific liver disease.

Bleeding disorders are classified based on the types of defects such as coagulation factor deficiencies, platelet disorders, vascular disorders or fibrinolytic defects. Hemophilia A and B and Von Willebrand’s disease are common bleeding disorders due to Coagulation factor Deficiencies. As the month of March is celebrated as Bleeding disorder awareness month, we have covered some of the common bleedings disorders with key companies operating in the market to address the therapeutics challenges in their management.

Haemophilia is classified based on the missing clotting factor in the blood. Hemophilia A is one of the most common genetic bleeding disorders caused by missing or defective factor VIII, a clotting protein, due to which it is also called factor VIII deficiency.

A consists of nearly 80% of the total patient pool of Hemophilia. Hemophilia A cases are categorised as mild, moderate and severe cases based on the severity of the diseases. Further, is it observed that moderate and severe cases consist of around 75% of the patient pools of Hemophilia A. As per the Delveinisght, the total Hemophilia A prevalent population in the 7MM was 43,243 in 2020, which is expected to rise during the study period.

As of now, there is no cure for Hemophilia A. Factor Replacement Concentrates, and Bypassing agents are the major treatment option for Hemophilia A. However, at present, some of the key pharma and biotech players are exploring the potential of gene therapy for Hemophilia A. Companies such as BioMarin Pharmaceutical, Novo Nordisk, Sanofi, Pfizer, Sangamo Therapeutics, Spark Therapeutics and many others are working on novel therapeutic approaches for Hemophilia A which is expected to change the outcome for the patients affected with it. Along with the launch of the upcoming therapies, the rise in healthcare spending is expected to provide stimulus to the Hemophilia A market growth.

Hemophilia B, also called factor IX deficiency , is caused by missing or defective factor IX, a clotting protein. Haemophilia B is the second most common type of haemophilia. Being male and family history are the two main risk factors for Hemophilia B, however, in some cases, females may also show some signs of bleeding. It is genetically passed down in the family, and it may also occur by spontaneous mutation. It is found to be more prevalent in the royal families of Spain, Germany, and Russia, due to which it is also known as the “Royal disease. Like other bleeding disorders, the Hemophilia B affected person may bleed longer than other people and internal bleeding into joints and muscles and external bleeding may also occur.

According to the Delveinsight analysis, in 2020,  the total Hemophilia B prevalent population in the 7MM in 2020 was 10,739 and expected to rise by 2030. The prevalent population of Hemophilia B in the United States was observed to be 4,134 cases in 2020.

Hemophilia B lacks a permanent cure; however, treatment options such as Recombinant Factor IX Concentrates, Plasma-Derived Factor IX Concentrates, and Fresh Frozen Plasma are available in the market. At present companies such as Novo Nordisk, Sanofi, Pfizer, Sangamo Therapeutics, Catalyst Biosciences, uniQure, and others are working on different therapeutic approaches for Hemophilia B.

Von Willebrand disease is the most common bleeding disorder that equally affects men and women; however, women are likely to show more symptoms than men. As per the CDC, in the United States, around 1% of the population which is roughly around 3.2 million, is found to be affected by Von Willebrand disease. VWD is inherited from one or both parents and caused by the absence or defect in the von Willebrand factor, a protein that helps in blood clotting. The signs and symptoms of Von Willebrand disease may vary from person to person according to the severity and types. The disease largely remains unnoticed for years until the episode of severe bleeding occurs after surgery or other such procedures.

Over the past few years, increased awareness and improved diagnostics tools have played a significant role in accessing Von Willebrand disease’s burden. According to Delveinsight, in 2017, the total diagnosed Von Willebrand disease prevalent population in seven major markets was observed to be 33,758. Among the 7MM, the United States accounted for the highest diagnosed prevalence.

As per the CDC, “between 2012 and 2016, more than 14,600 men, women, and children were seen at haemophilia treatment centres for the treatment of VWD, and about 2/3 were women and girls. The current VWD treatment option is categorised into three parts based on drugs administered, which includes Non-replacement Therapy, Replacement Therapy and Adjunct Therapy. To minimise the burden of the VWD, some of the key market players, such as Shire Plc., CSL Behring, LFB Biomedicaments SA, Octapharma AG, Grifols SA and many others are working on developing Von Willebrand disease therapies. The entry of the promising expanded recombinant therapies and regulatory approvals is expected to fuel the VWD market growth during the forecasted period.

Idiopathic thrombocytopenic purpura Idiopathic thrombocytopenic purpura is another blood disorder that results in an abnormal decrease in the number of platelets in the blood which can lead to bleeding gums, internal bleeding and excessive bruising. Occurring in both children and adults, ITP can cause purple bruises. Blood in the vomit, urine or stool, nosebleeds, bruising, uncontrolled bleeding during surgery or due to cut and gum bleeding are some of the most common symptoms of ITP. Apart from bleeding, diabetes, osteoporosis, cataracts are some of the most common complications of ITP.  Idiopathic thrombocytopenic purpura is diagnosed based on the medical and medication history, physical exam and complete blood count, the blood and urine tests.

As per the Delveinsight estimations, the total Idiopathic thrombocytopenic purpura prevalent population in the seven major markets was found to be 180,498 in 2017. The current ITP therapeutics market is marked with several first- and second-line therapies. The therapeutics approach for ITP aims to provide a platelet count that prevents major bleeding rather than correcting the platelet count to normal levels. Some of the pharma giants such as Biotest, UCB Biopharma, Argenx BVBA, GC Pharma, SK Plasma, Jiangsu HengRui Medicine, Argenx, Kezar Life Sciences, Bristol-Myers Squibb, Principia Biopharma, and Protalex hold the potential to improve the dynamics of  Idiopathic thrombocytopenic purpura market with the launch of potential therapies during the forecast period.

Worldwide a significant proportion of the population is living with different bleeding disorders and creates a significant challenge in term of diagnosis and treatment. It affects the quality of life of the patients and their life expectancy. However, to address the unmet need in the treatment market companies at the global level are conducting various clinical trials to provide safe and effective therapeutic options. Similarly, some of the companies are exploring the potential of gene therapy as a treatment option for haemophilia A. Overall, in the coming years, the launch of emerging therapies, rising awareness, increasing healthcare spending, and regulatory approval is expected to address several prevailing challenges in bleeding disorder treatment and management.

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Pfizer Vaccine Approval Key to Boosting Vaccination Rates

After weeks of anticipation, FDA has granted full approval for the Pfizer-BioNTech Covid-19 vaccine, raising hopes that this action will help overcome the vaccine hesitancy that has plagued efforts to broadly immunize the US population. The decision announced August 23, 2021 was no surprise, as staff in the Center for Biologics Evaluation and Research have been working overtime to review extensive clinical data contained in thousands of documents as quickly as possible. Consequently, FDA fully assessed the Pfizer biologics license application in 40% of the time allotted for this process, producing a decision that hopefully will “give people confidence to get vaccinated,” said CBER Director Peter Marks at a press conference. FDA Acting Commissioner Janet Woodcock termed the approval decision “a pivotal moment” in the fight against the pandemic, noting that the BLA should make the public “confident that this vaccine meets the FDA’s gold standards for safety, effectiveness, and manufacturing quality that we require for an approved product.”

The approved vaccine now carries the brand name Comirnaty, devised for the manufacturers by the Brand Institute to convey a sense of “community” and “immunization.” FDA notes that the manufacturers now may promote the vaccine according to its rules, efforts that hopefully will further encourage vaccination in the United States and elsewhere. Such uptake may be advanced by vaccination mandates from federal, state, and local government agencies. President Biden remarked that the BLA should be a signal to both public and private employers to move forward with vaccine requirements. The Pentagon has announced plans to mandate vaccination for military forces, both active duty and reserve units, while hospitals and nursing homes look to require such protection for all staffers.

The manufacturers note that Comirnaty has been administered to more than 1 billion patients around the world. Production is slated to increase from 1.2 billion vaccine doses so far to 3 billion this year and 4 billion doses in 2022, according to the manufacturers. The partners also plan to seek licensure of a third, or booster, dose via a supplemental BLA, and to extend full approval to individuals over 12 years of age. Patients ages 12 to 16 still can obtain the vaccine under the Emergency Use Authorization that remains in effect, as can immunocompromised individuals seeking a third booster shot to protect against the delta variant.

The BLA package submitted in May 2021 included longer-term follow-up data from its Phase III clinical trial plus extensive information on manufacturing and facilities. We didn’t “just look at data summaries,” commented Marks. He explained that the task of evaluating the Pfizer BioNTech BLA involved reviewing hundreds of thousands of pages of reports, including four months of follow-up data on half of the 40,000 clinical trial participants. Staff also visited sites where the clinical trials were conducted to ensure that the information was collected accurately and met all standards. FDA wanted to ensure “that we saw all adverse events,” Marks said, adding that FDA also did a full benefit-risk assessment based on real-world data for the hundreds of millions of patients that have received the vaccine over the past year.

The BLA review process also involved visiting numerous manufacturing facilities to ensure quality production. The manufacturers noted in a press release that there is no change in the formulation for Comirnaty and that providers may continue to use already distributed product obtained under the EUA.

The FDA approval letter for Comirnaty also specifies a number of post approval studies and commitments to further assess product safety and efficacy. These include additional studies on the risks for myocarditis and pericarditis after receiving Comirnaty, a side effect that has been seen and assessed by FDA, notably in younger male patients. The companies also will create a registry to monitor the vaccine’s impact on pregnant women and infants.

FDA’s action represents the agency’s first approval of a vaccine using messenger RNA technology, a move expected to further bolster R&D on therapies and preventives in this area. Further evidence of the vaccine’s safety and efficacy will hopefully encourage broader public vaccination and begin to rein in the now resurgent Covid-19 pandemic.

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Lessons learned from the Covid vaccine development process

As the world’s focus has turned to getting the COVID-19 vaccines out as widely and rapidly as possible, it’s easy to almost forget about the incredible global effort that developed them in record time. But it is important to take some time to reflect on the process that got us here, so that we can learn from it and celebrate the amazing researchers whose work is now saving so many lives.

Recently, BioNTech Co-Founder and CEO Ugur Sahin, MD spoke about the challenges that had to be overcome in developing the mRNA vaccines. His talk was followed by a panel discussion that featured Prof. Ozlem Tureci, MD, Co-Founder and CMO of BioNTech; Dr. Ivan Dikic, Professor of Biochemistry at Goethe University; and moderated by Richard Horton, FRCP FMedSci, Editor-in-Chief of The Lancet.

Prof. Sahin explained that a major lesson from the COVID-19 vaccine development push was that “you can do things faster if everyone is on board and everyone accepts that there is a huge medical need and we need to work together. So it’s about international collaboration but it is also about not taking any shortcuts. You can be faster without taking shortcuts.”

Prof. Tureci emphasized the importance of being prepared for failures and to “accept that the very nature of innovation is that you have to enter unknown territory and you have to navigate it. And that will come with unexpected situations, and not every attempt to solve a problem will be the final solution.”

She noted that, along with their teams, she and Prof. Sahin had been steeped in the innovation process for the last three decades, which means they have had plenty of experience encountering unknowns. “Our entire mode of action is that we move forward, ready to face the hurdles and technical problems and challenges which are thrown our way as they come,” she said. “And we trust that our team, and our partners, would be able to do that.”

This made them well-prepared for the high-intensity Covid vaccine development process where, as Prof. Tureci puts it, the sequence was “ready, shoot, aim, and not ready, aim, shoot meaning, explore a bit, and then react to the ripple effects we were generating.”

Prof. Sahin marveled at the scientific community’s ability to combine speed and accuracy, sharing new data very quickly but also pointed out that the system would also correct itself right away if there was a problem.

“For example, I read a paper which said that the receptor for this virus is upregulated in a certain population,” he said. “Two days later, another paper came out and said, no, we are not able to confirm that. And a few days later, a third paper came out and said we are also unable to confirm that.” As intense as the effort was, there was a culture of accountability that ensured that everyone remained focused on getting things right.

Prof. Sahin also had kind words for Elsevier’s role in the process. “I would like to thank Elsevier for the fantastic work that your team is doing. One of the key reasons why we have started and pivoted our cancer research to infectious disease vaccine was a paper that I had read in The Lancet. The paper was fantastic, timely and provided a clear guidance that this infection had all features to become a global pandemic.”

He commended Elsevier’s Coronavirus Research Hub as well. “In the weeks thereafter, you had created this wonderful COVID website. I was there two or three times a day in the morning and in the late afternoon and before sleeping to see what kind of news was there. This was really great work.”

He continued, “I was amazed how fast these papers were edited. And particularly also the graphics visualizing, for example, how infections are distributed and so on. So congratulations to your team. This team was part of the solution for this pandemic.”

Prof. Tureci also added her appreciation. “I can’t agree more,” she said, noting the important matter of trust among the research community. “Trust requires transparency and information, and every entity which contributes to that is an important part in this process. So please keep up the good work.