Virus World

For cardiologist Eric Topol, this week’s vaccine news presented a personal dilemma. Topol, who directs the Scripps Research Translational Institute and is a popular commenter on COVID-19 research, had hoped to get an updated COVID-19 vaccine from Novavax, rather than a messenger RNA (mRNA) shot from Pfizer or Moderna. Novavax relies on an older, protein-based approach that has shown long-lasting effects against other pathogens, and Topol wondered whether it might produce more durable protection. On Tuesday, it seemed he might get his chance: a drugstore he visited for an mRNA vaccine ran out of doses, and hours later the U.S. Food and Drug Administration authorized a Novavax shot well-matched to current COVID-19 variants. The green light marks the first time Novavax will be widely available to teens and adults. “It’s hard to know how it compares” to mRNA vaccines, Topol admits; there are no head-to-head studies to rely on. In clinical trials, Novavax appeared less likely than mRNA shots to cause side effects like headache and fatigue. But how does it stack up against mRNA vaccines when it comes to protection against SARS-CoV-2? The question has been vexingly difficult to answer.

Some hints are emerging, including the first large study of Novavax in the real world, published this week by a team in Italy. The results are far from definitive, but they suggest “there aren’t massive differences” between the vaccines, says Alberto Mateo Urdiales, an epidemiology and infectious disease researcher at the Italian National Institute of Health, who led the study. Whereas mRNA vaccines carry instructions for making a SARS-CoV-2 protein, Novavax directly delivers a fragment of that viral spike protein with an adjuvant for boosting immune response. Such protein subunit vaccines have yielded durable protection against various pathogens including hepatitis B and shingles, along with some respiratory ailments such as pneumonia. A version of the Novavax vaccine targeting the original SARS-CoV-2 variant was approved as a primary vaccination series and first booster in the United States in 2022; it also became available in Europe that year. Its tried-and-true technology appealed to some people wary of the new mRNA approach. And unlike the more fragile mRNA shots, it lasts for months in the refrigerator. But uptake has been low and the company is banking on more shots in arms this fall.

The Italian team tried to pin down how well the shot actually works, analyzing data on more than 20,000 Italians who had received two doses as their primary vaccine series in 2022. After 4 months, the vaccine was 55% effective at staving off symptoms from a SARS-CoV-2 infection and 28% effective at preventing infection altogether, the researchers reported in JAMA Network Open. That’s roughly comparable to how the mRNA vaccines have performed, Mateo Urdiales says. He cautions that the emergence of SARS-CoV-2 variants, repeated boosting, and swelling numbers of infections make it hard to compare numbers across the studies of effectiveness conducted to date. Smaller studies, meanwhile, have tried to address another reason a Novavax booster appeals to people like Topol: the possibility that “mixing and matching” various COVID-19 vaccines might provide better protection than any single vaccine brand. “There was theoretical hope that since these vaccines work in slightly different ways, they would have different strengths in terms of which part of the immune system they activate best,” says Angela Branche, an infectious disease specialist at the University of Rochester. She co-chairs a mix-and-match study called COVAIL that includes another protein subunit vaccine from the company Sanofi, which is not available in the U.S....

The Antiviral Program for Pandemics (APP) team, along with experts from across the National Institutes of Health (NIH) and Biomedical Advanced Research and Development Authority (BARDA), has drafted Target Product Profiles (TPPs) for potential direct-acting antiviral therapeutics candidates targeting several key viruses of pandemic potential.  These TPPs should be considered ‘living documents’ that are never final but may be useful starting points for consideration by therapeutics developers who are drafting TPPs for their specific candidates.  Also, the example TPPs are not intended to provide details about product requirements for funding or other support from USG or other funders.  Instead, these sample TPPs are being provided as tools for scientists working toward therapeutics product development of direct-acting antivirals for use in potential future outbreaks or pandemics. We are happy to receive feedback on these sample TPPs and may make updates/revisions or add TPPs for additional clinical indications in the future, so please monitor this page for updates and send any feedback to APPSubmissions@mail.nih.gov

The shots would be the first vaccines available against a respiratory virus that kills thousands and leads to many more hospitalizations each year.

Why It Matters: R.S.V. can be lethal

The F.D.A. estimates that R.S.V. is associated with 6,000 to 10,000 deaths each year in adults 65 and older and at least 60,000 hospitalizations in that age group. It is a leading killer of children worldwide.

This winter, R.S.V. contributed to the “tripledemic” also involving flu and Covid cases that swamped children’s hospitals and some I.C.U. wards.

Announcing the approval, Dr. Peter Marks, the agency’s vaccine division chief, said: “Older adults, in particular those with underlying health conditions, such as heart or lung disease or weakened immune systems, are at high risk for severe disease caused by R.S.V.”

Background: Benefits and risks of the shots

On March 1, an F.D.A. advisory panel reviewed data from trials for two R.S.V. vaccines aimed at older adults, one from GSK and one from Pfizer. The panel recommended that the agency approve both.

The GSK vaccine was nearly 83 percent effective in preventing lower respiratory tract illness in adults 60 and older in a study of about 25,000 patients, according to data published in The New England Journal of Medicine. The virus can lead to pneumonia, which is far more worrisome for the elderly.

Pfizer’s R.S.V. vaccine for older adults is also expected to receive F.D.A. approval this month. In a large study of that shot, it was found to be nearly 67 percent effective in preventing R.S.V.-related illness.

The Pfizer and GSK vaccines were even more effective in treating older and sicker patients.

The advisers did learn of some rare side effects from the vaccine trials. In the days after the shots were given, two recipients of the Pfizer vaccine and one recipient of the GSK shot developed cases of Guillain-Barré, a condition where the immune system attacks the nervous system, according to data presented to the F.D.A. panel.

Once the shots become available to the public, the agency said it would require GSK to monitor the incidence of Guillain-Barré and another rare condition that was possibly related to the shot.

Moderna is also developing an R.S.V. vaccine for this age group, and said it expected authorization in the first half of this year. A trial of 37,000 older adults showed 82 percent efficacy of its shot, the company said, with “no safety concerns identified” thoughanalyses were continuing.

AstraZeneca and Sanofi are seeking F.D.A. approval of a monoclonal antibody treatment to protect infants and toddlers up to 2 years old from R.S.V. infections. Findings of a major study showed the therapy reduced confirmed illnesses by 75 percent after one shot, according to AstraZeneca.

Pfizer has applied for separate approval of an R.S.V. vaccine to be given in the later stages of pregnancy to protect young infants.

What’s Next: When will the shots be available?

It will still be months before the adult vaccine is publicly available in the United States.

The Centers for Disease Control and Prevention is expected to follow the F.D.A.’s approval, most likely issuing its recommendation in June.

GSK said its vaccine would then be available in the fall at U.S. pharmacies, clinics and other health care settings.

GSK executives have said that supplies of the vaccine, which is manufactured mainly at a plant in Belgium, should be readily available. For Medicare patients with Part D drug coverage, there would be no out-of-pocket expense, Alison Hunt, a GSK spokeswoman, said. But the company has not released a price, although insurers typically cover much of the cost of many vaccines.

Last week, the European Medicines Agency recommended approval of GSK’s vaccine for adults 60 and older. The company said it hoped the shots would also be approved later for use in Japan and China.

Over the course of a two-day meeting, vaccine advisers to the US Food and Drug Administration voted in favor of approval for RSV vaccines for adults over the age of 60. The vaccine candidates, made by Pfizer and GlaxoSmithKline, could become the world's first approved vaccines against the common virus. On Wednesday, committee members voted 10-2 in support of the safety and unanimously in support of the effectiveness of GSK’s vaccine for the prevention of lower respiratory tract disease caused by RSV among older adults. For Pfizer’s shot, committee members voted on Tuesday with 7-4 with one abstention that there is adequate data to support the vaccine’s safety and effectiveness. The FDA, which typically follows the committee’s recommendations, is expected to decide on approval of the vaccines in May, ahead of RSV’s typical winter surge. Respiratory syncytial virus is a highly contagious virus that causes flu-like illness in people of all ages that increases in severity with age. According to the US Centers for Disease Control and Prevention, RSV is responsible for an estimated 177,000 hospitalizations and 14,000 deaths per year among adults 65 or older. GSK’s RSV vaccine candidate for older adults was 82.6% effective in preventing lower respiratory tract disease defined by either two or more symptoms or and one or more signs or three or more symptoms. The shot was 94.1% effective at preventing severe disease. The Pfizer vaccine was 66.7% effective at preventing moderated lower respiratory tract illness with two or more symptoms and 85.7% effective at preventing illness with three or more symptoms, according to Pfizer.

Focus on safety

Though a majority of the committee voted in support of the vaccines, some committee members expressed concerns over both vaccines’ risk of Guillain-Barre syndrome, a rare neurological disorder in which the immune system attacks its own nerves, causing muscle weakness and sometimes paralysis. The incidence of Guillain-Barre is about 1.5 to 3 cases for 100,000 adults over age 60 in the US annually, according to the FDA. Two adults among 20,000 vaccine recipients in Pfizer’s Phase 3 clinical trial developed symptoms consistent with the rare neurological disorder within nine days of receiving the shot. Of roughly 15,000 vaccine recipients of GSK’s Phase 3 clinical trial, one man developed Guillain-Barre syndrome within nine days of vaccination. “It seems to me that one case is a red flag. Two cases is very concerning,” said Dr. Marie Griffin, professor of health policy at Vanderbilt University Medical Center, who voted that the data demonstrated that both vaccines are effective but not safe

The FDA has called Guillain-Barre syndrome an “important potential risk” of Pfizer and recommended the company conduct a safety study for further evaluation of Guillain-Barre syndrome and other immune-mediated demyelinating conditions after potential vaccine approval, which the company has agreed to.

GSK has said they will closely monitor cases after approval. While Pfizer did not provide data on co-administration with other vaccines, GSK’s data showed potential safety risks when the RSV and flu shots were administered together. Two adults in their 70s who received both the flu and RSV vaccine developed acute disseminated encephalitis, a rare neurological disorder that involves swelling of the brain and spinal cord, and one of the individuals died. The FDA considers these cases as possibly related to either RSV or flu vaccination, but review is ongoing. “This is a disease with incidence 0.1 in 100,000 usually, the majority being in children and then a scatter in young adults. So two cases in elders within three to four weeks post-vaccine is highly anomalous from a statistical standpoint,” said Dr. Hana El Sahly, the FDA advisory committee chair, who voted against the GSK shot based on its safety profile but in favor based on efficacy. Dr. Adam Berger, who voted in favor of GSK’s vaccine based on safety and efficacy, says it seems to be an issue with co-administration and that concerns with acute disseminated encephalitis and Guillain-Barre syndrome won’t be answered until larger studies are conducted. “I suggest a heavy reliance on the postmarketing surveillance and not only just reliance but making sure there is an enforcement around the requirements about this,” Berger said. “At the moment, I think the profile seems to be within the acceptable range.”

Search for an effective RSV vaccine

Some vaccine advisers wanted to see more data on the Pfizer vaccine’s effectiveness at preventing hospitalization or death, especially among high-risk individuals including adults over 80, those with comorbidities, or those who are immunocompromised. “I think the data does support the effectiveness of this vaccine, it’s just the population was underrepresented by people who could most benefit from the vaccine,” Griffin said of Pfizer’s clinical trial. The available safety and efficacy data is from the first season of Pfizer’s clinical trial scheduled over two RSV seasons and the first of three seasons for GSK’s trial. Some experts want to wait for more data. “I’m desperately eager to have a vaccine that works for RSV. This has been a terrible disease my whole career. I would love to see it. No doubt about it,” said Dr. Jay Portnoy, professor of pediatrics at Children’s Mercy Hospital, who voted in support of GSK’s vaccine but against Pfizer based on efficacy. Portnoy said waiting for a second season of data would provide more robust numbers and complete analysis. “It’s not an emergency use authorization. We can take the time to finish the studies and get the information we need before licensing this product going forward. So I remain a little bit skeptical given the data that we have,” he said. Others think the benefits of the candidate vaccines outweigh the potential risks of deadly RSV infection. “Despite the challenges, despite the additional hurdles, our obligation is to do what’s right for the public,” said Dr. Daniel Kim who voted in favor of both shots. “And in this case, we have a bad disease, we have a good vaccine – so far, anyway, given the clinical trials – it’s a safe vaccine, and the vaccine can be used to prevent disease.”

The FDA has for the first time approved an emergency use authorization for a long-acting monoclonal antibody cocktail designed to prevent symptomatic COVID-19 among adults and children aged 12 years and older. According to data submitted to the FDA, AstraZeneca’s Evusheld (tixagevimab plus cilgavimab), also known as AZD7442, can reduce the risk for developing symptomatic COVID-19 by 77%, compared with placebo, among unvaccinated adults without prior SARS-CoV-2 infection at increased risk for inadequate immunization response.  Alfred H.J. Kim, MD, PhD, assistant professor of medicine in the division of rheumatology at the Washington University School of Medicine, in St. Louis, Missouri, noted that Wednesday’s approval represents a significant step forward in the protection of immunocompromised patients. “This is really great news for the immunosuppressed in general, but particularly those on medications that put them at high risk for very poor or absent antibody responses,” Kim told Healio Rheumatology. “These patients now have a way to have protective antibodies. The timing of this is especially good, since cases are spiking due to colder weather — and the holidays are coming up. If it can be administered prior to holiday engagements, this will provide an extra layer of protection for them.” According to Kim, the Evusheld EUA will have a particularly profound impact on patients receiving TNF inhibitors, as these individuals appear unable to neutralize the delta variant of the SARS-CoV-2 virus, even when vaccinated. Although COVID-19 booster shots can alleviate this concern, they may not be an option for patients who experienced adverse reactions to the vaccine.

“This pre-exposure prophylaxis (PrEP) can neutralize delta in these patients,” Kim said. “Given the number of people on TNF inhibitors, for rheumatoid arthritis, psoriatic arthritis, ulcerative colitis and more, this could help provide an extra protection that they don’t quite have right now. I should add that patients on TNF inhibitors who receive the booster dose can generate a response to delta. However, if they had a reaction to the vaccine, PrEP solid alternative.” Kim added that he and his colleagues will now focus on administering the newly available cocktail to their B-cell depleted patients, as well as those receiving mycophenolate, considering both populations are at risk for having an inadequate response to COVID-19 vaccines. The FDA’s EUA authorizes the drug only for adults and children aged 12 years and older, weighing at least 40 kg, who are not currently infected with SARS-CoV-2, and who have not recently been exposed to COVID-19. The emergency authorization also requires that individuals either have moderate to severely compromised immune systems, due to a medical condition or immunosuppressive medications or treatments, leading to a potentially inadequate immune response to COVID-19 vaccination, or a history of severe adverse reactions to a COVID-19 vaccine and/or components of the vaccines. Evusheld is not authorized for individuals to treat COVID-19 or for post-exposure prevention of COVID-19. The FDA also stressed that Evusheld is not a substitute for vaccination among those for whom vaccination is recommended.

The FDA based their approval on data from the phase 3 PROVENT trial, which examined the efficacy and safety of Evusheld in 5,197 participants across 87 sites in the United States, United Kingdom, Spain, France and Belgium. Participants were unvaccinated adults without prior SARS-CoV-2 infection who had an increased risk for inadequate response to active immunization, or an increased risk for COVID-19, including those whose location or circumstances increased their chances of infection. According to AstraZeneca, more than 75% of those enrolled demonstrated baseline comorbidities and other characteristics associated with an increased risk for severe COVID-19, including immunosuppressive disease or receiving immunosuppressive medications, diabetes, severe obesity or cardiac disease, chronic obstructive pulmonary disease, and chronic kidney and chronic liver disease. Participants were randomly assigned 2:1 to receive either a single, intramuscular 300 mg dose of Evusheld or a saline placebo, administered in two sequential injections. According to the PROVENT researchers, Evusheld reduced the risk for symptomatic COVID-19 by 77% (95% CI, 46% to 90%), compared with placebo. None of the participants who received the monoclonal cocktail developed severe COVID-19, and none died. Meanwhile, the placebo arm saw three cases of severe COVID-19, including two deaths. The trial reported a total of 25 cases of symptomatic COVID-19 across both groups at the primary analysis. Regarding safety, Evusheld was well tolerated, with the preliminary analyses demonstrating balanced adverse events between the placebo and treatment groups. AstraZeneca’s request for an EUA also included data from the phase 3 STORM CHASER trial, which analyzed efficacy and safety among more than 1,100 unvaccinated adults who were exposed to SARS-CoV-2 within the past 8 days. The study suggested that the cocktail shrunk the risk for symptomatic COVID-19 by 33% (95% CI, –26% to 65%), compared with placebo. However, this result was not significant, and the trial did not meet its primary endpoint.

The decision will set off a cascade of vaccine requirements by hospitals, colleges, corporations, and some state and local governments.  The Food and Drug Administration on Monday granted full approval to Pfizer-BioNTech’s coronavirus vaccine for people 16 and up, making it the first to move beyond emergency use status in the United States. The decision will set off a cascade of vaccine requirements by hospitals, colleges, corporations and other organizations. United Airlines recently announced that its employees will be required to show proof of vaccination within five weeks of regulatory approval. Oregon has adopted a similar requirement for all state workers, as have a host of universities in states from Louisiana to Minnesota. The Pentagon has said it would mandate the shots for the country’s 1.3 million active-duty troops once the Pfizer approval came through. The approval comes as the nation’s fight against the pandemic has intensified again, with the highly infectious Delta variant hurting 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 unvaccinated Americans who are eligible for shots to get them.

“While millions of people have already safely received Covid-19 vaccines, we recognize that for some, the F.D.A. approval of a vaccine may now instill additional confidence to get vaccinated,” Dr. Janet Woodcock, the acting F.D.A. commissioner, said in a statement. “Today’s milestone puts us one step closer to altering the course of this pandemic in the U.S.” Pfizer said it presented the F.D.A. with data from 44,000 clinical trial participants in United States, the European Union, Turkey, South Africa and South America. The company said the data showed the vaccine was 91 percent effective in preventing infection — a slight drop from the 95 percent efficacy rate that the data showed when the F.D.A. decided to authorize the vaccine for emergency use in December. Pfizer said the decrease reflected the fact that researchers had more time to catch people who became infected.  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 that they would be more likely to get vaccinated with a shot that had been fully approved. The Pfizer-BioNTech vaccine will continue to be authorized for emergency use for children ages 12 to 15 while Pfizer collects the necessary data required for full approval. A decision on whether to authorize the vaccine for children younger than 12 could be at least several months away. So far, more than 92 million Americans — 54 percent of those fully inoculated — have gotten Pfizer shots. Most of the rest received Moderna’s vaccine. Dr. Peter Marks, the F.D.A.’s top vaccine regulator, said that the Pfizer vaccine’s licensure followed a rigorous review of hundreds of thousands of pages of data and included inspections of the factories where the vaccine is produced. “The public and medical community can be confident that although we approved this vaccine expeditiously, it was fully in keeping with our existing high standards for vaccines in the U.S.,” he said.

The F.D.A. is in the midst of a decision-making marathon related to coronavirus vaccines. The next major one looming for regulators is whether or not to authorize booster shots. The Biden administration said last week that pending the agency’s clearance, it will offer third shots to adults who got the Pfizer and Moderna vaccines eight months after their second injection, starting Sept. 20.  Federal health officials said that both Pfizer-BioNTech 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 health experts have challenged the decision to recommend booster shots as premature, saying the data shows that the vaccines are holding up well against severe disease and hospitalization, including against the Delta variant. Boosters would only be warranted if the vaccines were failing to prevent hospitalizations with Covid-19, some of those experts have said. Regulators are still reviewing Moderna’s application for full approval of its vaccine. That decision could take several weeks. Johnson & Johnson is expected to apply soon for full approval.

The U.S. Food and Drug Administration gave an emergency use authorization to the antibody treatment developed by Vir Biotechnology (VIR.O) and GlaxoSmithKline (GSK.L) for treating mild-to-moderate COVID-19 in people aged 12 years and older.  The antibody drug, Sotrovimab, is not authorized for patients who are hospitalized due to COVID-19 or require oxygen therapy, the health regulator said on Wednesday. (https://bit.ly/3uorQZ8) Sotrovimab belongs to a class of drugs called monoclonal antibodies, which mimic natural antibodies that the body generates to fight off infection. The antibody treatment will be available for COVID-19 patients in the coming weeks, GSK and Vir said, adding that they plan to submit a marketing application to the FDA in the second half of 2021.  Similar COVID-19 therapies by Regeneron Pharmaceuticals (REGN.O) and Eli Lilly (LLY.N) have been authorized for emergency use in the United States. The European Union's drug regulator last week backed the use of Sotrovimab for COVID-19 patients who were at risk of severe disease and do not need supplemental oxygen.

FDA Emergency Use Authorization Letter (May 26, 2021):

https://www.fda.gov/media/149532/download 

Glaxo Press Release (May 26, 2021):

https://www.gsk.com/en-gb/media/press-releases/vir-biotechnology-and-gsk-announce-vir-7831-reduces-hospitalisation-and-risk-of-death-in-early-treatment-of-adults-with-covid-19/ 

"Having this treatment available for some patients provides an alternative for managing this chronic condition," said FDA's John Farley.  In a move that could transform HIV treatment, the Food and Drug Administration has approved a monthly injectable medication, a regimen designed to rival pills that must be taken daily. The newly approved medicine, which is called Cabenuva, represents a significant advance in treating what continues to be a highly infectious disease. In 2018, for instance, there were approximately 36,400 newly infected patients living with HIV in the U.S., according to the Centers for Disease Control and Prevention. About 1.7 million people worldwide became newly infected in 2019, according to UNAIDS. Although several medicines exist for treating HIV, ViiV Healthcare is banking on the improved convenience of getting a monthly shot, even if it must be administered by a health care provider. The company, which is largely controlled by GlaxoSmithKline (GSK), gathered data showing nine of 10 patients in pivotal studies claimed to prefer the shot over taking pills each day.

“This approval will allow some patients the option of receiving once-monthly injections in lieu of a daily oral treatment regimen,” said John Farley, who heads the Office of Infectious Diseases in the FDA’s Center for Drug Evaluation and Research, in a statement. “Having this treatment available for some patients provides an alternative for managing this chronic condition.” Two clinical studies of more than 1,100 patients from 16 countries found that Cabenuva was as effective in suppressing the virus as the daily, oral, three-drug regimens that were taken by patients throughout the 48-week study period. However, patients must first take an oral version of the injectable medicine and another pill for the first month before pivoting to monthly shots, according to the FDA.  The cost, however, is steep — the list, or wholesale, price is $3,960 a month, or more than $47,500 a year. The list price for the one-time initiation dose is $5,490. However, a ViiV spokeswoman explained that a 30-day oral “lead-in,” which is required as part of the approval, will be made available at no charge to patients. She also maintained the list price for the monthly shot is “within the range” of HIV treatment pills on the market today. There is also considerable competition from Gilead Sciences (GILD), which markets several HIV medicines. During 2019, its HIV treatment franchise generated $17.2 billion in revenue, a 12.5% year-over-year increase, and grabbed more than 80% of the market for patients starting HIV therapy, according to Cowen analyst Phil Nadeau. He expects HIV medication sales to hit $24.4 billion in 2025, but points to HIV prevention pills as big drivers of that increase. ViiV, meanwhile, is developing an every-other-month injectable in hopes of capturing a more substantial market share.

Last November, an interim analysis found cabotegravir – a component of Cabenuva – was 89% more effective in preventing infection among women than Truvada, a Gilead pill that must be taken daily and is the current standard of care. And a separate analysis released in July showed the every-other-month shot protected uninfected people by 66% more compared with Truvada in at-risk men and transgender women who have sex with men. “We see Cabenuva as the beginning of long-acting treatment for HIV,” said Kimberly Smith, who heads global research and medical strategy at ViiV, who expects to seek FDA approval for this version of the shot in coming weeks. “We’re opening the door with Cabenuva and will only create more hunger for other long-acting therapies. It really becomes a sort of anchor.” The approval, by the way, comes more than a year after ViiV hoped to win approval for the treatment. In late 2019, the FDA issued a so-called complete response letter and explained approval could not be granted at the time due to issues with chemistry, manufacturing and controls, which are used to determine safety, effectiveness and quality.

FDA News Release (Jan 21, 2021):

https://www.fda.gov/news-events/press-announcements/fda-approves-first-extended-release-injectable-drug-regimen-adults-living-hiv#

- First at-home, virtually guided service to bring rapid, reliable and affordable testing into the home where the result is delivered in minutes

- Abbott and eMed™ expect to deliver and administer 30 million BinaxNOW™ tests in the first quarter of 2021, with an additional 90 million in the second quarter

- $25 cost for the test and service is the lowest available for at-home testing, which supports the home user to ensure a successful testing process

- BinaxNOW is a highly portable, easy-to-use, 15-minute antigen test with no instrument that detects the virus when people are most infectious, which is critically important in slowing the spread of the virus

- Service uses Abbott's complementary NAVICA™ app to enable the testing process and display authenticated BinaxNOW test results verified by a trained guide - and supports consumer confidence in testing at home

ABBOTT PARK, Ill.,, Dec. 16, 2020 /PRNewswire/ -- Abbott (NYSE: ABT) announced today that the U.S. Food and Drug Administration (FDA) has issued Emergency Use Authorization (EUA) for virtually guided at-home use of its BinaxNOW™ COVID-19 Ag Card rapid test for detection of COVID-19 infection. Abbott is bringing BinaxNOW, the most affordable and widely distributed rapid test into the home, where the result is delivered in minutes without the need to send it out for processing. The $25 cost for the test and service is the lowest currently available for at-home testing.  To facilitate the delivery of the BinaxNOW test to the home and the guided collection and testing process, Abbott has partnered with digital health solutions provider eMed™. This agreement furthers Abbott's vision of making as many tests as possible available in a variety of different settings to improve accessibility, support consumer confidence in testing at home, and help people start returning to living their daily lives with more normalcy. Abbott and eMed expect to deliver and administer 30 million BinaxNOW at-home tests in the first quarter of 2021, with an additional 90 million in the second quarter. Scale is critical to provide broad access to people who need testing and Abbott has scale for all its eight COVID-19 lab and rapid tests. In fact, since launching BinaxNOW in August, Abbott has ramped up capacity to 50 million tests a month in its U.S. facilities that are currently being distributed through the federal government and is expanding further so even more people have access to the tests.

"As the pandemic has evolved, the need for rapid testing has only grown. Unfortunately, we're still hearing that many people can't access testing as quickly as they need it," said Robert B. Ford, Abbott's president and chief executive officer. "That's why Abbott is bringing our rapid BinaxNOW test and NAVICA platform into homes through this partnership with eMed, which allows us to maintain the integrity of the testing process, get even closer to people who need testing and help provide the confidence we need to help get back to living with a bit more normalcy." The eMed service offering costs $25 a test, and eMed takes care of determining eligibility, the guided self-collection process, public health reporting requirements and gets people their results through their NAVICA app in a matter of minutes. The eMed offering could also remove some of the obstacles that individuals, governments and organizations face when seeking to provide or perform testing. These include mobility issues for people with disabilities or who may not have a reliable form of transportation, inconvenient testing windows for people who work non-traditional hours or have childcare or eldercare responsibilities, and discouragingly long lines at testing centers.

FDA Release Dec. 16, 2020:

https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-issues-new-authorization-binaxnow-covid-19-ag-card-home-test

The Food and Drug Administration’s first analysis of the clinical trial data also found that the coronavirus vaccine worked well regardless of a volunteer’s race, weight or age. The coronavirus vaccine made by Pfizer and BioNTech provides strong protection against Covid-19 within about 10 days of the first dose, according to documents published on Tuesday by the Food and Drug Administration before a meeting of its vaccine advisory group. The finding is one of several significant new results featured in the briefing materials, which include more than 100 pages of data analyses from the agency and from Pfizer. Last month, Pfizer and BioNTech announced that their two-dose vaccine had an efficacy rate of 95 percent after two doses administered three weeks apart. The new analyses show that the protection starts kicking in far earlier. What’s more, the vaccine worked well regardless of a volunteer’s race, weight or age. While the trial did not find any serious adverse events caused by the vaccine, many participants did experience aches, fevers and other side effects. “This is what an A+ report card looks like for a vaccine,” said Akiko Iwasaki, an immunologist at Yale University.

On Thursday, F.D.A.’s vaccine advisory panel will discuss these materials in advance of a vote on whether to recommend authorization of Pfizer and BioNTech’s vaccine. Pfizer and BioNTech began a large-scale clinical trial in July, recruiting 44,000 people in the United States, Brazil and Argentina. Half of the volunteers got the vaccine, and half got the placebo. New coronavirus cases quickly tapered off in the vaccinated group of volunteers about 10 days after the first dose, according to one graph in the briefing materials. In the placebo group, cases kept steadily increasing. The vaccine’s swift impact could benefit not just the people who get it but the country’s strained hospitals, curbing the flow of new patients into intensive care units. Despite the early protection afforded by the first dose, it’s unclear how long that protection would last on its own, underscoring the importance of the second dose. Previous studies have found that the second dose of the Pfizer-BioNTech vaccine gives the immune system a major, long-term boost, an effect seen in many other vaccines.

The efficacy of the vaccine after the first dose is about 52 percent, according to Dr. William C. Gruber, senior vice president of Pfizer Vaccine Clinical Research and Development. After the second dose, that rises to about 95 percent. “Two doses of vaccine provide maximum protection,” he said. Many experts have expressed concern that the coronavirus vaccines might protect some people better than others. But the results in the briefing materials indicate no such problem. The vaccine has a high efficacy rate in both men and women, as well as similar rates in white, Black and Latino people. It also worked well in obese people, who carry a greater risk of getting sick with Covid-19. Some vaccines for other diseases set off a weak immune response in older adults. But Pfizer and BioNTech found that people over 65 got about as much protection from the coronavirus vaccine as younger people did. Even if the vaccine is authorized by the F.D.A., the trial will continue. In the briefing documents, the companies said that they would encourage people to stay in the trial as long as possible, not knowing whether they got the vaccine or the placebo, so that the researchers could continue to collect information about whether the vaccine was safe and effective...

FDA documents for Dec. 10 meeting available here:

https://www.fda.gov/media/144246/download

https://www.fda.gov/media/144245/download 

The Food and Drug Administration approved the first gene therapy for Duchenne muscular dystrophy, but limited access to those ages four and five. In an eagerly anticipated decision, the Food and Drug Administration Thursday approved the first gene therapy for muscular dystrophy. "Today's approval addresses an urgent unmet medical need and is an important advancement in the treatment of Duchenne muscular dystrophy, a devastating condition with limited treatment options, that leads to a progressive deterioration of an individual's health over time," said Dr. Peter Marks, director of the FDA's Center for Biologics Evaluation and Research, in a statement. But the agency rejected a request to make the treatment available to all children with Duchenne muscular dystrophy, the most common form of the incurable muscle disease, who could still walk. Instead, the agency restricted access to patients ages four and five until more evidence is available that the therapy is safe and effective. The decision elicited mixed reactions. Parents of children suffering from the genetic disorder, advocates and some doctors and researchers welcomed the limited approval. But some were disappointed the treatment isn't being made more widely available right away. "Today is a very important day," Debra Miller, who leads CureDuchenne, an advocacy group, told NPR in an interview. "But every single day these boys are losing muscle cells. And so when you have a son with Duchenne and you see them getting weaker right before your eyes, you know we have to get therapies to patients sooner rather than later."

FDA's accelerated approval came with limits

Others, however praised the agency's restraint, though some argued even the limited approval was premature. "This is a really critical decision for the FDA to get right," Dr. Caleb Alexander of Johns Hopkins University told NPR in an interview. Alexander voted against approval during a May meeting of an FDA advisory committee that narrowly recommended the agency grant approval. "This has implications not only for those who may receive this product. But it also sends an important signal regarding what the FDA will require for future products to treat this and similarly devastating diseases," Alexander said. The company that developed the treatment, Sarepta Therapeutics of Cambridge, Mass., said the therapy would be available as soon as possible. The treatment, called Elevidys, will cost $3.2 million for each patient, the company announced shortly after the approval. Sarepta asked the FDA to approve the gene therapy under a program that allows the agency to provide access to treatments before direct evidence is available that they are effective. But this accelerated approval process is controversial because some companies fail to follow through on their promises to confirm their treatments work. A drug approved this way to prevent premature birth was recently withdrawn after being found useless. Sarepta's muscular dystrophy treatment is the first gene therapy approved under the program. The disease, which almost exclusively affects boys, destroys muscles. Most boys end up in wheelchairs before they become teenagers. Eventually, their hearts and lungs give out. Most people with the disease die in their 30s or 40s. The gene therapy works by infusing trillions of harmless viruses in single treatment that has been genetically modified to ferry a gene to patients' muscles.

Evidence for the gene therapy is indirect

The gene produces a miniature version of a protein called dystrophin, that boys with muscular dystrophy are missing or don't have enough of. The hope is this "micro-dystrophin" will at least help slow the progression of the disease. But there's an intense debate about this. Sarepta based its request on how much micro-dystrophin it produces in patients' muscles — without direct evidence that's actually helping alleviate symptoms and prevent disease progression. During the May advisory meeting, parents and doctors showed dramatic videos of children who could barely stand and walk, running, biking and and easily climbing stairs after the treatment. But Alexander and other experts say it remains unclear the treatment is responsible and is safe. "This product is not without risks. And I think the evidence is murky," Alexander says. "The evidence really doesn't meet the bar required to reach market." And children who receive the treatment may then be ineligible to get other treatments in the pipeline that may be more effective. "That's a really non-trivial concern," Alexander said.

But others said there is sufficient evidence to warrant broader approval, including preliminary evidence the treatment is improving boys' muscles, as well as animal data and clear evidence the therapy boosts micro-dystrophin in muscles. "What's the old expression: 'Don't let perfect get in the way of good?' " said Jeffrey Chamberlain, who directs the Muscular Dystrophy Research Center at the University of Washington. That said, Chamberlain was glad the FDA at least approved the treatment for younger children pending further data. "You'd like to see approval for as broad a range of patients as possible. But we'll take what we can get at this point," Chamberlain said. Michael Kelly, the chief scientific officer for CureDuchenne, says he hopes this will lead to other, even more effective gene therapies for the disease. "This is a critical and really important step in treatment and this is going to lead the way and blaze a trail for the next round of better therapeutics," Kelly told NPR in an interview.

The Food and Drug Administration (FDA) on Thursday granted full approval to Pfizer’s COVID-19 oral antiviral pill Paxlovid for use in adults who are at high risk for progression to severe disease. The agency’s approval comes nearly a year and a half after the drug received an emergency use authorization, and as hospitalization and deaths from the virus continue to decline. The agency’s approval comes nearly a year and a half after the drug received an emergency use authorization, and as hospitalization and deaths from the virus continue to decline. Paxlovid is given as a 5-day treatment course, and FDA said it should be initiated as soon as possible after a diagnosis of COVID-19 has been made, but no more than five days after symptom onset.  The drug is specifically advised for use in people aged 50 and older as well as those who suffer from certain medical conditions that put them at high risk of developing complications, including hospitalization and severe disease from COVID-19. In March, an FDA independent advisory committee recommended the agency fully approved Paxlovid, finding the medicine was safe and effective for treating COVID-19 in high-risk adults based on three of Pfizer’s clinical trials.  The agency further said Paxlovid does not cause “rebound” COVID-19 infection. 

Paxlovid has been shown to be most effective among patients who have not received a COVID-19 vaccine and those who have not been previously infected. One of Pfizer’s clinical trials showed Paxlovid significantly reduced the proportion of people with COVID-19 related hospitalization or death by 86 percent compared to placebo among patients treated within five days of symptom onset, and 89 percent in those treated within three days, “Today’s approval demonstrates that Paxlovid has met the agency’s rigorous standards for safety and effectiveness, and that it remains an important treatment option for people at high risk for progression to severe COVID-19, including those with prior immunity,” said Patrizia Cavazzoni, director for the FDA’s Center for Drug Evaluation and Research. “The FDA remains committed to working with sponsors to facilitate the development of new prevention and treatment options for COVID-19,” she said. The federal government owns 1.1 million doses of Paxlovid that it already purchased, that are available at pharmacies nationwide. Once that stockpile is used up, distribution will shift to the private sector, and Pfizer will sell directly to health providers. The company sells to the government for about $530 for a 5-day course of treatment, but has not said what it will charge commercially.

FDA Press Release (May 25, 2023):

https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-antiviral-treatment-covid-19-adults 

The FDA approved the first oral fecal microbiota productopens in a new tab or window for preventing recurrent Clostridioides difficile infections in adults, the agency announced on Wednesday. Developed as SER-109 and given the trade name of Vowst, the therapy is indicated for patients who have already received a course of antibiotics for recurrent C. difficile infections. SER-109 -- which involves four pills taken once a day for 3 consecutive days -- contains live bacteria from donor fecal matter, with the donors and stool screened for a slew of pathogens. Despite that, the agency still warns that the product carries the potential risk of transmitting infectious agents or food allergens. "Today's approval provides patients and healthcare providers a new way to help prevent recurrent C. difficile infection," Peter Marks, MD, PhD, director of the FDA's Center for Biologics Evaluation and Research, said in a statement. "The availability of a fecal microbiota product that can be taken orally is a significant step forward in advancing patient care and accessibility for individuals who have experienced this disease that can be potentially life-threatening."

Approval was supported by the randomized ECOSPOR III trialopens in a new tab or window and an open-label studyopens in a new tab or window conducted in the U.S. and Canada. In ECOSPOR III, which involved 182 patients with recurrent infections but with symptoms under control following a course of antibiotics, patients assigned to SER-109 had significantly lower recurrence rates of C. difficile infection through 8 weeks compared with those assigned to placebo (12.4% vs 39.8%, P<0.001). Results were consistent across age groups and largely held up at 24 weeks, at 21.3% in the SER-109 group and 47.3% for the placebo group. C. difficile infections can cause a host of symptoms (diarrhea, abdominal pain, fever) and organ failure or death in severe cases. One of the most common healthcare-associated infections, these infections are linked with anywhere from 15,000 to 30,000 deaths each year. While standard treatment involves antibiotics, these can alter the microbiome and allow C. difficile to return, and few treatments exist for recurrent infections, which are more likely to affect immunocompromised individuals, people over 65, and those who are hospitalized or living in nursing homes. Recurrent C. difficile infection is a highly debilitating and life-threatening disease," said Carl Crawford, MD, of Weill Cornell Medical College in New York City, in a statementopens in a new tab or window from developer Seres Therapeutics, adding that antibiotics alone do not address the underlying cause of recurrent infections -- "dysbiosis of the gut microbiome."

FDA Press release (April 26, 2023):

https://www.fda.gov/news-events/press-announcements/fda-approves-first-orally-administered-fecal-microbiota-product-prevention-recurrence-clostridioides 

But the company that created the 30-minute, over-the-counter test has filed for bankruptcy, so the product’s eventual availability to consumers remains unclear. The Food and Drug Administration issued an emergency authorization for the first over-the-counter, at-home combination flu and Covid test on Friday, just two days after the company that makes the test announced that it had filed for bankruptcy protection based, in part, on the agency’s lengthy approval timeline. The single-use test works with a self-collected nasal swab and provides a result in about 30 minutes, according to the F.D.A. The test is meant to be used by people 14 and older, or by an adult collecting a sample from someone age 2 or older. The test’s developer, Lucira Health, based in California’s Bay Area, announced its bankruptcy plan on Wednesday, noting that it had expected its emergency-use authorization for the test in August before the onslaught of the flu season. The company said the agency’s authorization process “became protracted,” and said it had high expenditures as it moved forward with manufacturing the combination tests. Without revenue that the company expected from projected sales of the tests during this year’s flu season, Lucira decided that it would pursue a sale of its business but continue operations to serve customers, according to its news release. The bankruptcy plan was reported earlier in The Wall Street Journal.

Agency urged to authorize fourth U.S. vaccine despite some concern about rare heart inflammation as a side effect.  A key committee of advisers to the U.S. Food and Drug Administration (FDA) today recommended nearly unanimously that the agency grant an emergency authorization to a COVID-19 vaccine from Novavax, opening the way for the first protein-based COVID-19 vaccine to become available to people in the United States. The 21-0 vote, with one abstention, marks a hard-won and long-sought milestone for the small Gaithersburg, Maryland-based biotechnology company that was moribund as the pandemic began. It found a new life as it collected $2 billion to develop a vaccine, first from an international organization that supports vaccinemaking and then from the U.S. government. “This is a case study of perseverance,” Bruce Gellin, chief of global public health strategy at the Rockefeller Foundation, said after the vote. Yet Gellin was the lone abstaining vote, saying the committee wasn’t given data on how the vaccine performs against the Omicron variants now circulating, or for how many months its protection lasts. Still, Gellin said, “This vaccine has incredible potential.” It is easy to store and transport, lasting at refrigerator temperatures for months, unlike the dominant messenger RNA (mRNA) vaccines. The thumbs up from the FDA advisers likely means the agency will allow the company to enter the U.S. market, as FDA usually follows its advisers’ lead. Novavax hopes that holdouts skeptical of mRNA vaccines and, ultimately, others seeking booster shots, will opt for its tried-and-true technology.

If it wins final authorization, the vaccine will be the fourth COVID-19 jab marketed in the United States. Unlike the other three, which deliver genetic material that directs host cells to make the coronavirus’ spike protein, Novavax’s product delivers spike protein directly to recipients. Approved vaccines for shingles, hepatitis B, and influenza use similar protein-based technology.  Just days before today’s meeting, the company’s stock price tumbled when FDA published data indicating that the vaccine may rarely cause myocarditis and pericarditis, a problem that has also dogged mRNA vaccines from Moderna and Pfizer-BioNTech. Perhaps in response to the volatility, NASDAQ froze trading of the stock today before the meeting opened. But 21 of the 22 advisers concluded that any risk posed by heart inflammation was outweighed by the benefits of a vaccine that showed 90.4% efficacy against early strains of SARS-CoV-2 in a trial involving 30,000 people in the United States and Mexico. The Novavax shot also has low “reactogenicity”—meaning immediate side effects, from painful arms to malaise. The committee recommended authorization for the two-shot series in adults 18 years and older. “Certainly the benefits outweigh the risks,” said adviser Michael Nelson, an allergist and immunologist at the University of Virginia School of Medicine. But in response to a query from Doran Fink, acting deputy director of FDA’s vaccine approval branch, Nelson said the agency should include a warning about heart risks in the package insert. “It would be a travesty if we didn’t mention this in the … documentation for the public to show the concern that we have.” Novavax’s vaccine, which is produced in insect cells and combined with an immune-boosting substance called an adjuvant, has already been authorized in more than 40 countries including the United Kingdom, Canada, Germany, and Australia; it has also won emergency authorizations from the European Union and the World Health Organization.  But manufacturing issues have hampered Novavax’s effort and sidelined its would-be U.S. vaccinemaking facilities. In addition, the company struggled mightily to show it could make the vaccine consistently. If authorized in the United States, the product will initially be manufactured, as all Novavax vaccine currently is, by the Serum Institute of India, one of the world’s largest vaccine manufacturers. Myocarditis concerns may also dog the vaccine. The data revealed on 3 June by FDA described five cases of myocarditis that occurred in people in the vaccine arms of the Novavax clinical trials in the United States and the United Kingdom. Four occurred within 20 days of vaccination, a time frame during which there were no cases in the placebo arm. Three cases were in men ages 16 to 20. Young men have had the highest rates of myocarditis or pericarditis after receiving mRNA vaccines. “These events raise the concern for a causal association with this vaccine, similar to the association documented with mRNA COVID-19 vaccines,” FDA wrote.

An FDA advisory panel voted in favor of authorizing the Pfizer/BioNTech Covid-19 vaccine for children between the ages of 5 and 11. After sometimes tense deliberations that weighed the benefits of vaccination against potential risks, the Vaccines and Related Biological Products Advisory Committee voted 17-to-0 with one abstention on Tuesday that two 10-microgram doses of the vaccine should be granted emergency use authorization, a clearance that will remain in effect only as long as the pandemic is considered a public health emergency.  The FDA is not bound by the votes of its advisory committees, which it convenes to ask for guidance, but it generally follows their advice. Before the vaccine becomes available, it will also need to be reviewed by another committee, the Advisory Committee on Immunization Practices, which is convened by the Centers for Disease Control and Prevention, and the CDC director will need to affirm the ACIP’s decision. Pfizer and BioNTech presented data from a study of 1,518 children who received the 10-microgram vaccine — one-third the adult dose — and another 750 who received placebo. The vaccinated volunteers were 90.7% less likely to develop symptomatic Covid, and when they did become ill, their symptoms were less severe.

The panel weighed the benefits of preventing Covid-19 against the risks of the vaccine, in particular the risk of the heart conditions myocarditis and pericarditis, which, though hard to measure exactly, appear to occur once per every 10,000 or so boys and young men vaccinated. The cases seen after use of the vaccine appear to be milder than regular cases of the inflammatory condition, and last for a shorter time. The panel agreed with the FDA’s own scientists that the risk of Covid during the pandemic far outstripped the risk of myocarditis, even if transmission of the virus is relatively low in a given area. More than that, panelists felt that there were some children who definitely needed access to the vaccine. Many said that they were leaving it to the CDC’s ACIP committee to make recommendations regarding which children should receive the vaccine.  In an analysis released before the meeting, FDA analysts used mathematical modeling to estimate how many hospitalizations would be prevented if a million boys ages 5 to 11 were vaccinated at six different points in the pandemic in the United States. At most points, the vaccine would prevent 200 to 250 hospitalizations per every million boys vaccinated. At points when transmission of the virus was low, the vaccine would only have prevented only 21 hospitalizations per 1 million boys. The analysts said that while that suggests the vaccine might trigger slightly more myocarditis-related hospitalizations in boys than Covid-19 hospitalizations it would prevent in the same population, the benefits still might outweigh the risks, given that Covid cases that require hospitalization are generally more severe than myocarditis cases. The FDA also said that its estimate of myocarditis risk was “conservative,” meaning that the risk for children in the 5 to 11 age group might be lower.

– First smallpox antiviral approved for all age groups, including infants, and patients who have difficulty swallowing -

DURHAM, N.C., June 04, 2021 (GLOBE NEWSWIRE) -- Chimerix (NASDAQ:CMRX), a biopharmaceutical company focused on accelerating the development of medicines to treat cancer and other serious diseases, today announced that the U.S. Food and Drug Administration (FDA) has granted TEMBEXA® (brincidofovir) tablets and oral suspension approval for the treatment of smallpox. TEMBEXA is approved for adult and pediatric patients, including neonates. “We are delighted to report our first FDA approved products for the treatment of smallpox, particularly as the importance of pandemic preparedness has been put into focus over the last year. With this approval in hand, we now look forward to advancing our discussions with the Biomedical Advanced Research and Development Authority (BARDA) toward a procurement contract to support national preparedness,” said Mike Sherman, Chief Executive Officer of Chimerix. Chimerix developed the TEMBEXA oral formulations as medical countermeasures for the treatment of smallpox under an ongoing collaboration with BARDA, part of the office of the Assistant Secretary for Preparedness and Response within the U.S. Department of Health and Human Services, under contract number HHSO100201100013C. TEMBEXA’s approval is based on efficacy data in two lethal orthopoxvirus animal models of human smallpox disease, the rabbitpox model (New Zealand White rabbits infected with rabbitpox virus) and the mousepox model (BALB/c mice infected with ectromelia virus). In the pivotal studies in each model, TEMBEXA treatment resulted in statistically significant survival benefit versus placebo following delayed treatment after animals were infected with a lethal viral dose. The FDA’s ‘Animal Rule’ allows for testing of investigational drugs in animal models to support effectiveness in diseases which are not ethical or feasible to study in humans. The TEMBEXA U.S. Prescribing Information has a BOXED WARNING for increased risk for mortality when used for longer duration; see below for Important Safety Information.

About Chimerix

Chimerix is a development-stage biopharmaceutical company dedicated to accelerating the advancement of innovative medicines that make a meaningful impact in the lives of patients living with cancer and other serious diseases. Most recently, the Company obtained FDA approval for brincidofovir as a medical countermeasure for the treatment of smallpox. The Company has two other advanced clinical-stage development programs, ONC201 and dociparstat sodium (DSTAT). ONC201 is currently in a registrational clinical program for recurrent H3 K27M-mutant glioma and a blinded independent central review is expected later in 2021. DSTAT is in development as a potential first-line therapy in acute myeloid leukemia.

About Smallpox

Smallpox is a highly contagious disease caused by the variola virus. Historically, smallpox was one of the deadliest diseases in history with a case fatality rate of approximately 30%. Despite successful eradication of smallpox in the 1970s, there is considerable concern that variola virus could reappear, either through accidental release or as a weapon of bioterrorism. According to the U.S. Centers for Disease Control and Prevention (CDC), variola virus is ranked in the highest risk category for bioterrorism agents (Category A) due to its ease of transmission, high mortality rate, and potential to cause public panic and social disruption.

About TEMBEXA

TEMBEXA is an oral antiviral formulated as 100 mg tablets and 10 mg/mL oral suspension dosed once weekly for two weeks. TEMBEXA is indicated for the treatment of human smallpox disease caused by variola virus in adult and pediatric patients, including neonates. TEMBEXA is not indicated for the treatment of diseases other than human smallpox disease. The effectiveness of TEMBEXA for the treatment of smallpox disease has not been determined in humans because adequate and well-controlled field trials have not been feasible and inducing smallpox disease in humans to study the drug’s efficacy is not ethical. TEMBEXA efficacy may be reduced in immunocompromised patients based on studies in immune deficient animals. TEMBEXA (brincidofovir) is a nucleotide analog lipid-conjugate designed to mimic a natural monoacyl phospholipid to achieve effective intracellular concentrations of the active antiviral metabolite, cidofovir diphosphate. Cidofovir diphosphate exerts its orthopoxvirus antiviral effects by acting as an alternate substrate inhibitor for viral DNA synthesis mediated by viral DNA polymerase.

FDA Press Release (June 4, 2021):

https://www.fda.gov/drugs/drug-safety-and-availability/fda-approves-drug-treat-smallpox 

As a condition of the emergency use authorizations issued for the Pfizer/BioNTech and Moderna coronavirus vaccines, those companies are expected to work toward asking the US Food and Drug Administration for full approval -- and some health officials are hoping it will happen soon.  These vaccines have been in use since mid-December under emergency use authorizations, known as EUAs. During the pandemic, real-world data have shown the vaccines are effective against the coronavirus that causes Covid-19. Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, told CNN's Jim Sciutto on Wednesday he hopes Covid-19 vaccines will receive full FDA approval "very soon," and that the FDA will work "as expeditiously as possible" on approval applications for coronavirus vaccines as they come in. Progressing from authorized to approved would allow manufacturers to market and directly distribute their vaccines. It could also have an impact on vaccine mandates -- and perhaps sway skeptics hesitant to get the vaccines now.

The approval sets the stage for widespread inoculations in the United States with a second coronavirus vaccine.  As the coronavirus continued to surge across the United States, an independent panel of experts advising the Centers for Disease Control and Prevention voted on Saturday to endorse a second coronavirus vaccine for use in the United States. The committee’s recommendation follows an emergency authorization granted by the Food and Drug Administration on Friday. The committee’s endorsement now awaits final approval by Dr. Robert R. Redfield, director of the C.D.C., expected shortly. Some 5.9 million doses of the Moderna vaccine are slated for distribution starting on Sunday, and the first inoculations are expected to begin sometime on Monday. Unlike the Pfizer-BioNTech vaccine, which was authorized for use in people 16 and older, Moderna’s vaccine is approved only for people 18 and older. While Pfizer began clinical trials of its vaccine in children as young as 12 in October, Moderna did not begin its pediatric studies until this month and does not expect to have complete data on safety and efficacy until sometime next year.

Much of the committee’s deliberations centered on the severe allergic reactions reported in several cases following injections of the Pfizer-BioNTech vaccine, which contains ingredients similar to those in Moderna’s recipe. Six cases of anaphylaxis have now been documented in the United States, and two in Britain. Several milder allergic reactions have occurred, as well. More than 272,000 doses of the Pfizer-BioNTech vaccine have already been doled out nationwide as of Saturday, according to the C.D.C. Allergic reactions to vaccines typically occur at a rate of about one in a million. Dr. Grace Lee, a pediatrician and vaccine expert at Stanford University, noted at the committee meeting that the estimates so far seemed to indicate that the risk of these events associated with the Pfizer-BioNTech vaccine “does seem qualitatively higher than for most typical vaccines.” Still, she added, “for me, personally, it doesn’t necessarily change the risk-benefit balance of the Covid-19 vaccine at this time.” Dr. Thomas Clark, an epidemiologist at the C.D.C., noted that people who experience anaphylaxis after getting a shot shouldn’t receive a second dose. It’s still unclear whether an ingredient in Pfizer’s vaccine was the direct cause of the reactions.

Some experts have pointed to polyethylene glycol, or PEG, a chemical found in many pharmaceutical products, including laxatives like Miralax, that has very rarely been found to cause allergic reactions. Both the Pfizer-BioNTech and Moderna vaccines contain PEG, though in slightly different formulations.  Dr. Sarah Mbaeyi, a medical officer at the C.D.C., said the agency was recommending that people who know they have severe allergies to any ingredient in the vaccines abstain from getting the shots for now. People with a history of anaphylaxis to other vaccines or injectable therapies should consult their doctors and linger on site for monitoring for 30 minutes after their inoculation in case they start feeling sick. (Everyone else — including people who react strongly to other substances like food, pollen or pet dander, and people with mild allergies of any sort — may leave after 15 minutes.) Three severe allergic reactions were reported in Moderna’s clinical trials, which included more than 30,000 adults, half of whom received a placebo instead of the vaccine. None were believed to be linked to the vaccine.  At the meeting, experts also raised concerns about four cases of a temporary facial paralysis called Bell’s palsy, three of which occurred in the vaccine group in the Moderna trial. (Four cases of Bell’s palsy also arose in Pfizer’s trials, all in the vaccine group.) There’s no evidence yet that directly links the paralysis to either vaccine, and Dr. Jacqueline Miller, a senior vice president at Moderna, said her company was continuing to monitor vaccine recipients for the side effect....

An initial shipment of about 2.9 million doses of the vaccine will be sent around the United States over the next week. The Food and Drug Administration authorized Pfizer’s Covid-19 vaccine for emergency use on Friday, clearing the way for millions of highly vulnerable people to begin receiving the vaccine within days.  The authorization is a historic turning point in a pandemic that has taken more than 290,000 lives in the United States. With the decision, the United States becomes the sixth country — in addition to Britain, Bahrain, Canada, Saudi Arabia and Mexico — to clear the vaccine. Other authorizations, including by the European Union, are expected within weeks. The F.D.A.’s decision followed an extraordinary sequence of events on Friday morning when the White House chief of staff, Mark Meadows, told the F.D.A. commissioner, Dr. Stephen Hahn, to consider looking for his next job if he didn’t get the emergency approval done on Friday, according to a senior administration official who spoke on condition of anonymity because he was not authorized to discuss the matter. Dr. Hahn then ordered vaccine regulators at the agency to do it by the end of the day. The authorization set off a complicated coordination effort from Pfizer, private shipping companies, state and local health officials, the military, hospitals and pharmacy chains to get the first week’s batch of about three million doses to health care workers and nursing home residents as quickly as possible, all while keeping the vaccine at ultracold temperatures.

U.S. regulators Wednesday approved the first drug for the treatment of Ebola. The Food and Drug Administration OK'd the drug developed by Regeneron Pharmaceuticals for treating adults and children with the Zaire Ebola virus strain, the most deadly of six known types. It typically kills 60% to 90% of patients. The drug was one of four tested during an outbreak in Congo that killed nearly 2,300 people before it ended in June. Survival was significantly better in study participants given Regeneron’s Inmazeb or a second experimental drug. The study was ended ahead of schedule last year so all patients could get access to those drugs. Regeneron’s treatment is a combination of three antibodies that work by killing the virus. It’s given once by IV. “When you have three drugs that bind to the (virus), there’s a low probability that the virus can evade all of them,” said Leah Lipsich, who heads Regeneron’s global program for infectious diseases. She said that should help prevent the virus from becoming resistant to the drug.

Seeking U.S. approval first is a common strategy for drugmakers developing treatments for diseases mainly found in the tropics and in developing countries. The FDA’s action will make it easier for Regeneron to get approval or allow emergency use during outbreaks in African countries, where the approval process is not straightforward, Lipsich said. The study in Congo involved 681 people, who were give one of four treatments. After four weeks, about a third of those who got Regeneron’s drug had died. Results were about the same for a second drug. But about half had died among the groups given one of the other two drugs, ZMapp or remdesivir. Gilead Science’s remdesivir is now being used as a treatment for coronavirus. Ebola is very contagious and is spread mainly through contact with body fluids from infected people. Symptoms include fever, muscle pain, vomiting, kidney and liver damage, and sometimes internal and external bleeding. The FDA approved the first vaccine for Ebola last December. The U.S. government, which helped fund the approved drug’s development, will buy thousands of doses over the next six years to go into the Strategic National Stockpile. Ebola cases are rare in the U.S., but occasionally are diagnosed in travelers returning from areas with an outbreak.

FDA release (Oct. 14, 2020):

https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-ebola-virus