FDA to allow mixing and matching of COVID-19 boosters

 The U.S. Food and Drug Administration is planning to allow Americans to get a different booster shot of a COVID-19 vaccine than the one initially taken, the New York Times reported on Monday.

The FDA in September authorized a booster dose of Pfizer Inc and partner BioNTech's two-shot COVID-19 vaccine for those aged 65 and older and some high-risk Americans.

The regulator's advisory panel has also backed the use of Moderna Inc and Johnson & Johnson's COVID-19 vaccine booster shots.

The government would not recommend one shot over another, and it might note that using the same vaccine as a booster when possible is preferable, the NYT report https://nyti.ms/3vmBRYE said, citing people familiar with the agency's plans.

The FDA declined to comment on the matter.

U.S. health officials have been under pressure to authorize the additional shots after the White House announced plans in August for a widespread booster campaign pending approvals from the FDA and the U.S. Centers for Disease Control and Prevention.

A study by the National Institutes of Health last week showed people who got Johnson & Johnson's COVID-19 vaccine as a first shot had a stronger immune response when boosted with vaccines from Pfizer and Moderna.

https://news.yahoo.com/u-fda-allow-mixing-matching-221119325.html

Actemra shortage spills over to include Sanofi’s rival Kevzara

 Roche’s Actemra has been in high demand since its value in treating severe COVID-19 was established, leading to shortages. Now, Sanofi’s rival therapy Kevzara has also been hit by supply constraints.

Sanofi said in a statement that supply of all four formats of Kevzara (sarilumab) – 150 mg or 200 mg pre-filled syringes or auto-injectors – will be short until early 2022 based on current demand.

Back in August, Roche’s Genentech unit said it was facing unprecedented demand for Actemra (tocilizumab) – known as RoActemra in some markets – caused by the spread of the highly-transmissible delta variant of SARS-CoV-2.

Usually used to treat rheumatoid arthritis, Actemra was granted emergency approval in June for hospitalised patients 2 years of age and older who are receiving systemic corticosteroids and need respiratory support after it was shown to reduce mortality in a clinical trial.

Shortly after, there were widespread reports of patients with rheumatoid arthritis and other inflammatory diseases on Actemra’s label struggling to get access to their treatment.

As supplies became tight, the National Institutes of Health (NIH) recommended that using Kevzara as an alternative to Actemra, as the two drugs act in the same way, inhibiting the IL-6 receptor and blocking the runaway inflammatory cascade that can wreak havoc in severe COVID-19.

The US agency made the recommendation even though Kevzara is not approved or authorised for emergency use for the treatment of COVID-19 anywhere in the world.  In fact, Kevzara failed trials in patients severely or critically ill and hospitalised with COVID-19.

Sanofi said it is “working diligently to manage supply to minimise the impact of this increase in demand,” and will “continue to prioritise access for indicated patients with rheumatoid arthritis.

In August, the World Health Organization (WHO) called on Roche to license out the technology needed to make Actemra to other manufacturers, so that production capacity could be ramped up as quickly as possible.

Last month, the drugmaker told Livemint.com it would not take legal action against Indian drugmaker Hetero after it announced plans to start making tocilizumab, and said it would encourage other manufacturers who are able to produce the drug to do so “without the delay of licensing negotiations or legal uncertainty in relation to our…patent rights.”

https://pharmaphorum.com/news/actemra-shortage-spills-over-to-include-sanofis-rival-kevzara/

Califf re-joining FDA would be positive for industry: analyst

 With rumours growing that that ex-FDA head Robert Califf looks set to receive President Joe Biden’s nomination to be the next FDA commissioner, at least one analyst thinks the appointment would be a positive for the biopharma industry.

Califf was appointed to the helm of the FDA under the Obama administration in 2016, and picked up a reputation for cracking down on manufacturing and safety, as well as defending the agency’s independence, before the change in administration saw his time come to an end just 11 months later.

According to RBC Capital Markets analyst Brian Abrahams, Califf has a “better than even” chance of being nominated and ultimately getting the job, because he is an uncontroversial choice, has prior experience, and “could lead the FDA with a steady hand.”

Interim FDA commissioner Janet Woodcock is due to stand down on 15 November, and her attempt to claim the job permanently has been undermined by criticisms about her handling of the opioid painkiller crisis in the US whilst in charge of the Centre for Drug Evaluation and Research (CDER).

Califf would inherit an agency under fire over some controversial regulatory approvals such as Biogen’s Alzheimer’s drug Aduhelm (aducanumab), and as it prepares to make key decisions on COVID-19 and the future role of vaccines and drug treatments.

After his stint at the agency Califf, returned to his role as a cardiologist whilst also serving as a health policy and strategy advisor to Google’s unit life sciences unit Verily.

He also founded Duke University’s Health Data Science Centre, so is likely to accelerate the FDA’s move towards integration of technology and healthcare if appointed to the role.

“We would expect an impact on [the] biotech space across a number of different fronts, both positive and negative, though skewing more positively,” said Abrahams.

Biotechs developing complex drugs like gene and cell therapies may face a tougher time under Califf given his track record of issuing warning letters for non-compliance with manufacturing standards, but he has also been a strong advocate of reforming clinical trials to make them more efficient and reduce costs.

Abrahams also notes that Califf was one of a number of FDA Commissioners who added their names to a letter taking former president Donald Trump to task, saying the White House was exerting too much influence over the FDA.

“We believe…that he may more forcefully oppose pressure on future vaccine/booster discussions, and act to shield the agency from the political process,” he said, adding that he may also be more willing to override advisory committee recommendations.

Califf had his own share of controversy whilst acting as the FDA commissioner, notably the controversial approval of Sarepta’s Exondys 51 for Duchenne muscular dystrophy, although the analyst noted that he was also highly critical of the company’s publication of a key study and called for it to be retracted.

When it comes to the ongoing fallout over Aduhelm’s approval, Abrahams thinks Califf would support reimbursement whilst more evidence of benefit is collected, rather than having opposition to continued availability of the drug.

“We continue to believe establishment of a permanent commissioner would improve perceived regulatory stability and provide another tailwind – alongside an improving earnings outlook, pickup in M&A activity, and drug pricing policy gridlock – to help the sector begin to appreciate again after this past year’s weakness,” concluded Abrahams.

https://pharmaphorum.com/news/califf-re-joining-fda-would-be-positive-for-industry-analyst/

Despite Merck oral COVID drug, antibodies by Regeneron, GSK, others have billions in sales ahead: analyst

 The success of Merck & Co.'s oral antiviral against COVID-19 immediately triggered concerns over the market prospect of antibody therapies. But, as one analyst sees it, those antibody products by Regeneron, GlaxoSmithKline and other companies still have an important role to play that pills can’t make up for.

COVID antibodies still have billions in sales with continuing strong demand at least into 2022 despite the possible availability of oral drugs, SVB Leerink analyst Geoffrey Porges predicted in a Friday note to clients.

Merck’s Ridgeback Biotherapeutics-partnered molnupiravir may capture a large share of the treatment market, but antibodies will likely benefit from a longer treatment window and could have an area all to themselves. Antibodies can potentially be used for disease prevention—both before and after exposure—and can offer long-term protection, Porges noted.

Current distribution data from the U.S. Department of Health and Human Services suggest an average 190,000 doses of COVID antibodies each week despite a recent decrease in new COVID cases. To Porges, this suggests “antibodies are finally being incorporated into routine treatment practices and protocols.” Over the next six to 12 months, supply of COVID antibodies will still be constrained, he estimated.

At the current run rate, the Department of Health and Human Services will need to ship 4.9 million doses of antibody drugs to meet demand over the next six months, but the existing contract only covers 2.7 million, leaving a “supply gap” of 2.2 million doses for the next six months alone, Porges noted.

Regeneron’s cocktail, REGEN-COV, is taking the lion’s share of the current market. The company recorded $3.5 billion sales from the drug in the first half of 2021 and recently signed a $2.94 billion contract with the U.S. government to supply an additional 1.4 million doses by January 2022.

Eli Lilly’s combo of bamlanivimab and etesevimab has seen limited use thanks to its reduced potency against coronavirus variants. GSK and Vir Biotechnology’s recently authorized sotrovimab is gaining steam, with Wall Street expectations of $503 million in 2021 sales.

In addition, a few days ago Brii Biosciences started a rolling submission for an emergency use authorization of its dual-drug regimen, BRII-196/198, setting up a potential decision in early 2022. In a National Institutes of Health-run phase 3 trial, the combo significantly reduced hospitalization and death over placebo in nonhospitalized patients.

More importantly, compared with treatment initiation within five days into symptomatic infection, BRII-196/198 showed similar efficacy when administered up to 10 days after symptom onset. Most small-molecule antivirals need to be given in a relatively tight time window early in infection to be efficacious, Porges noted. Molnupiravir, for example, was given in the first five days after symptom onset in its clinical trial.

For the Brii product, Porges projected $1.3 billion in stockpile orders from the U.S. and Chinese governments. The Street’s consensus currently puts the Sino-American biotech’s 2022 revenue at $485 million, according to Porges.

Besides treating certain mild to moderate patients, Regeneron’s and Lilly’s antibody combos are also used in the so-called post-exposure prophylaxis settings to prevent symptomatic disease in people who’ve come in contact with infected individuals in households.

AstraZeneca has recently filed for emergency use authorization of its antibody cocktail, AZD7442. The drug reduced the risk of symptomatic COVID by 77% in the pre-exposure prophylaxis setting among immunocompromised people, who typically don’t respond as well to vaccines.

Oral drugs likely won’t be able to reach the prevention market given their mechanism, Porges said. By comparison, antibody drugs’ ability to stay active in the human body for a long time gives them the ability to offer longer-term protection against COVID. Therefore, “[t]argeted prophylactic administration could become a key use case for COVID antibodies as public health authorities try to ringfence regional or facility-localized outbreaks,” Porges said.

Eventually, convenience of administration and duration of protection will be “important differentiators” within the antibody class, Porges noted. AZD7442 comes in an intramuscular formulation, and REGEN-COV has an under-the-skin version, while others are so far only infusions.

https://www.fiercepharma.com/pharma/merck-oral-covid-19-drug-molnupiravir-antibodies-regeneron-glaxosmithkline-brii-billions

Novo Nordisk teams with CVS on obesity support program ahead of Wegovy DTC launch

 As Novo Nordisk gears up to disrupt the obesity market with its newly approved weight-loss drug Wegovy, it is teaming with retail pharmacy giant CVS Health on a new education and nutrition coaching program for people taking anti-obesity meds.

The program, offered both virtually and in person, builds on existing nutrition coaching services CVS already offers at some of its HealthHUB locations. It includes a personal nutrition assessment, body composition tests, coaching sessions with a dietician, healthy meal coupons and an app where patients can find resources like shopping lists and recipes.

The CVS pilot targets people who have already been prescribed an anti-obesity drug and directs them to resources that can help them better understand how to properly use their medication, the companies said.

Though the program is unbranded, it fits well with Novo's strategies for rolling out Wegovy, which are “very much patient-directed," commercial chief Camilla Sylvest said on an investor call just after the drug won approval.

For now, CVS and the Danish drugmaker are testing the personalized program at three locations in the Phoenix area, but they expect to expand to new markets soon if the pilot goes well, Novo Nordisk’s director of media relations, Michael Bachner, said in an email interview. He said the pharma-pharmacy partnership is a first for both companies.

Gary Loeber, CVS Health’s executive vice president for pharmaceutical contracting and purchasing, said in a news release that the retail health chain has been “evolving our legacy relationships with pharmaceutical manufacturers to more fully support patients" and that the Novo partnership "recognizes people who struggle with weight loss often face stigma and need personalized support."

The pilot comes just months after the FDA greenlighted Novo Nordisk’s Wegovy (a higher dose of its diabetes drug Ozempic) as a treatment for obesity, which affects more than 40% of the U.S. population and often leads to other chronic diseases like heart disease, stroke and Type 2 diabetes.

The FDA based its approval, which came in June, on late-stage testing that found the drug helped patients achieve and sustain an average of 15% weight loss over 68 weeks. Novo also makes weight-loss drug Saxenda which, in contrast, has been shown to help patients lose 5% of their body weight, on average.

The company has been ramping up efforts ahead of its DTC launch to spread awareness of obesity as a chronic disease that can be treated with medication rather than just a lifestyle condition. It’s also rolled out a physician education site called Rethink Obesity to jump-start conversations about the disease.  

“Although obesity is a serious chronic disease, it is often misunderstood, underdiagnosed, and undertreated,” Doug Langa, Novo's executive vice president for North America, said in announcing the CVS partnership. “We have been working to change that because people who live with this disease need more care and support.”

While Novo is revealing few details about its timeline for introducing Wegovy to consumers via advertising, Langa told Fierce Pharma in a June interview that it has “big promotional plans” for the drug. 

https://www.fiercepharma.com/marketing/novo-nordisk-teams-cvs-health-obesity-support-program-ahead-wegovy-dtc-launch

Esperion cuts 40% of workforce, goes all in on cholesterol drug's outcomes trial

 Just as Esperion’s cholesterol sister meds Nexletol and Nexlizet launched at the start of the pandemic, pharma marketing went virtual. As its cash dwindles, the company is reaching for the ax.

Esperion is cutting 40% of its workforce, or about 170 employees, to reduce costs by at least $80 million a year in 2021 and 2022, the Michigan-based drugmaker said Monday. 

The company admitted it’s facing challenges with the launch of Nexletol and Nexlizet during the pandemic. Now, it'll further shift its marketing strategy toward digital outreach.

“In-person access to health care providers has been negatively impacted by the ongoing COVID-19 pandemic.,” Esperion’s newly minted CEO Sheldon Koenig said in a statement. The firm will focus on “an optimized blend of focused outreach including a streamlined salesforce, directed to targeted cardiologists and primary care physicians, and a suite of digital initiatives,” it said.

Esperion earned FDA green lights for Nexletol and Nexlizet to be used alongside statin for patients with high LDL cholesterol in February 2020, on the eve of COVID-19 becoming a global health crisis. Nexlizet is a combo of Nexletol and Organon’s—previously Merck’s—Zetia.

The oral drugs have been struggling to gain traction during the pandemic, generating just $17 million in the first half of the year. For the third quarter, Esperion expects revenues of $10.5 million to $11 million.

In the meantime, the slow ramp-up of Nexletol and Nexlizet is straining Esperion’s balance sheet. The company’s cash as of Sept. 30 was $153.7 million, down from $219.2 million in June and $305 million at the end of 2020.

The cash decline came despite some extra financing help recently. In April, Esperion secured $50 million from Oberland Capital under a revenue-based funding agreement. It also persuaded partner Daiichi Sankyo to pay up $30 million to expand their licensing agreement to cover additional ex-U.S. territories.

Koenig was brought on to right the ship. The former Sanofi cardiovascular franchise head jumped from Portola Pharmaceuticals to become Esperion’s chief operation officer in December and took over as CEO from longtime captain Tim Mayleben in mid-May.

Before Esperion, PCKS9 injectables from Amgen and a partnership between Sanofi and Regeneron were already duking it out in LDL-c, and Amarin offers Vascepa as an oral option. Those therapies have one thing in common: They all have approvals reflecting their ability to reduce heart-related events.

Esperion’s now also betting its future on all-important cardiovascular outcomes data. Savings from a leaner organization will enable its continued investment on a Nexletol outcomes trial, dubbed Clear, which Esperion expects to post top-line results in the first quarter of 2023. If successful, the trial could expand Nexletol’s addressable patient population from about 8 million to 19 million and could significantly reduce the drug’s current reimbursement hurdles, according to an Esperion presentation.

Meanwhile, Novartis is also trying to enter the LDL-c market with an oral PCSK9 drug, inclisiran, approved in Europe under the brand Leqvio. After a manufacturing inspection-related complete response letter, Novartis has refiled the high cholesterol therapy in July with a new production location.

Despite the financial hardship, Esperion in December shelled out $12.5 million upfront to license a preclinical oral PCSK9 candidate from Serometrix.

https://www.fiercepharma.com/marketing/covid-esperion-cuts-40-workforce-all-nexletol-cholesterol-drug-s-heart-outcomes-trial

On Covid-19 booster shots, the FDA has overstepped its role

 Booster shots for all adults six months after being vaccinated against Covid-19 are safe, effective, and badly needed. The United Kingdom and the European Union have authorized them for all adults. Israel won’t let anyone enter the country without one.

In the U.S., however, the FDA authorized a booster dose of the Pfizer/BioNTech Covid-19 vaccine only for individuals over age 65, those who face elevated risk due to their health conditions, or who work in jobs that put them at higher risk of infection.

In imposing these limits, the FDA overstepped its role for vaccine approvals.

The FDA fully approved the Pfizer vaccine — granting it a biologics license application — in August. The FDA’s role in approving the Pfizer Covid-19 booster is to review safety and efficacy. Its job does not include balancing “public” costs against benefits, nor deciding who gets priority to receive vaccines. Congress assigned the Centers for Disease Control and Prevention as the lead agency for public health policy for infectious diseases with input from the National Institutes of Health.

The safety of the Pfizer Covid-19 booster is similar to the first two doses. Millions of booster shots have been delivered, in the U.S. and elsewhere. There is no increased risk for myocarditis (an inflammation of the heart muscle that is the most important side effect) with a third dose versus a second, and that risk is meaningful only for young men. Even for them, however, the risk is very low and vastly outweighed by the risks of Covid-19 infection.

The FDA recognized this safety profile when it authorized booster shots for those in “at risk” groups.

The evidence for effectiveness is still emerging, but what is known today is ample. Results from Israel indicate that a booster dose greatly lowers the risk of severe illness. Boosters also prevent infection. This reduces the spread of SARS-CoV-2 among vaccinated and unvaccinated individuals. It isn’t yet clear how long protection from boosters will last, but the world can’t wait to find out. The waning effectiveness seen in multiple studies in Israel, in the U.S., and elsewhere implies that serious illness and death among recipients of the Pfizer vaccine will increase without boosters.

The evidence that booster shots are needed is overwhelming. Israel provides the best data because it vaccinated its populace with the Pfizer vaccine early and has excellent population data. Six months after vaccination, the country saw sharply lower protection against infection. A major booster campaign turned the tide against a surge in infections, hospitalization, and death due to the highly infectious Delta variant.

The risk of Covid-19-related hospitalization, which was near zero soon after vaccination, has also risen sharply — up tenfold since early this year. The roughly 98% protection found early on is now down to 77% in one recent study, and low- to mid-80s in others.

The FDA, in judging who most needs a booster, is arrogating powers it does not have. If approval for those over 65 is a “no-brainer,” as the FDA’s top vaccine official, Peter Marks stated, and reduces the Covid-19 risk for them and health care workers, so too for everyone else. Safety is the same. Efficacy is the same. Younger people face lower absolute risk from Covid-19 but deciding on vaccine priority is not the FDA’s role.

The FDA is a science agency, not a policy agency. It is required by law to approve a booster shot if it is safe (this is not in reasonable dispute) and effective, a threshold normally satisfied by being non-inferior to the original, approved vaccine (also not in dispute). As Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, told Kaiser Health News, “there’s very little doubt that the boosters will be beneficial. The Israelis already have that data in spades. They boost, they get an increase by tenfold in the protection against infection and severe disease.”

Limited access to boosters means more infections, hospitalizations, and deaths. The Covid-19-related death rate in the U.S., already at the top of the scale among advanced economies, will rise further. The economy will underperform as people stay home due to fear of infection.

There are also less obvious consequences. Millions of people are getting boosters by claiming to be eligible or simply not disclosing prior vaccination. This “self-help” will often be among the well-educated and well-informed, and thus will increase the large disparities in Covid-19 sickness and death seen so far in the U.S. Moreover, measuring how many people were vaccinated once, twice, or thrice will become a guessing game.

The reputation of U.S. regulatory agencies, already diminished by prior Covid-19 missteps, will drop further. People who want booster shots will hear: “The government wants to keep me from getting a booster. Other countries can get boosters, but not us.”

Early this year, when the vaccine supply was limited, most Americans accepted the need to give priority to the elderly and health care workers. Not so when the message is, “We have ample vaccine supplies but won’t give them to you.”

There is another way. The FDA should authorize the Pfizer booster for all adults aged 18 years and older six months after initial vaccination, and should do the same for the Moderna and J&J boosters. These stand in a different regulatory posture, due to the FDA’s slowness in granting full approval. But the FDA’s expertise is still in science, not public health policy. The need for a Moderna booster is lower than for Pfizer, due to slower decline in efficacy against infection. But people who received the less-effective J&J vaccine have especially strong need for a booster, which significantly improves efficacy.

There is also increasing evidence supporting mixing and matching vaccines. This should be allowed, as it is in the U.K. Recipients of the J&J vaccine should be able to get a Pfizer or Moderna booster, yet the FDA has punted on this issue.

The FDA can’t cure many Americans’ reluctance to get vaccinated. But it should stay in its own regulatory lane and get out of the way of the majority of vaccinated Americans who, informed by guidance from the CDC and medical advice, can make their own decisions on getting a booster, how soon, and which one.

Bernard Black is professor of law and finance at Northwestern University. David Thaw is professor of computing & information and law at the University of Pittsburgh. Both have extensively studied the Covid-19 pandemic.

https://www.statnews.com/2021/10/18/booster-shots-fda-overstepped-role/