Covid-19 roundup: Boehringer pulls a drug out of the pipeline for a PhII Covid-19 trial; Novavax delays PhIII trial in US, with PhII data coming Friday
With big questions still hanging over the fate of the vaccines and drugs now in late-stage development for Covid-19, Boehringer Ingelheim is pulling one of its early-stage drugs into a Phase II trial to see if it can help some of the most severely afflicted patients.
Put through a safety study last year, researchers have been intrigued by the potential of BI 764198 — a TRPC6 inhibitor — as a treatment for acute respiratory distress syndrome (ARDS), which can cause immense damage and death for patients exposed to the virus.
As the pandemic hit, “we started to ask, what are the mechanisms we have in the pipeline, what might help these patients?” says Clive Wood, head of discovery research at Boehringer. That led them to a drug in development for chronic kidney disease, which shares a pathway that could have an impact on the virus.
“We are far from having a clear path to having a clear path to the end of this situation,” says Wood, and that makes it important to recruit 90 patients for the Phase II, with the ability to pivot into a late-stage registration study if it works out.
Even if it doesn’t work out in time for Covid-19, Boehringer’s researchers expect that success could pave the way to other uses in the future. Right now, the only thing they know for certain is they need to see if it works. — John Carroll
Manufacturing delay pushes back the launch of a PhIII at Novavax
Though Novavax $NVAX is near the forefront of the Covid-19 vaccine race, it will be starting its Phase III trial later than anticipated.
The company said Tuesday that its late-stage study in the US has been pushed back to the end of November after delays in upscaling its manufacturing processes. That’s about one month after previously reported timelines.
Meanwhile, trial data from a separate Phase III being conducted in the UK are likely coming sometime “early” in the first quarter, Novavax said, adding that the results from this study “are expected to serve as the basis for global licensure.” Novavax did not elaborate on what that meant nor how they plan to apply for such “licensure” in the US.
Additionally, new Phase II data from the company’s ongoing Phase I/II trial are expected to come Friday. Investors mostly greeted the news warmly, as the company’s shares rose about 3% in Tuesday trading.
While there haven’t been any Covid-19 vaccine approvals or EUAs thus far, there have been a few for treatments. The FDA recently granted approval for Gilead’s remdesivir, marketed as Veklury, in hospitalized patients older than 12. That followed an EUA for the therapy, as well as EUAs for hydroxychloroquine and convalescent plasma. Regulators have since revoked the former’s authorization.
Novavax received a $1.6 billion Warp Speed contract in July and began its UK Phase III study in late September. The biotech is testing a two-shot regimen of its lower, 5 µg dose of protein antigen currently in Phase II, plus a 50 µg Matrix‑M adjuvant. The shots are being administered 21 days apart.
Pfizer currently leads Endpoints News’ Covid-19 vaccine race tracker, with Novavax coming in 8th. — Max Gelman
CBER director promises ‘safe and effective’ vaccine in op-ed
In an effort to shore up trust in the FDA’s ability to authorize a safe and effective vaccine, CBER director Peter Marks broke down the EUA process in a USA Today op-ed.
“We hope to ensure public confidence in COVID-19 vaccines by being transparent about FDA’s decision-making process,” he wrote. “Whether a vaccine is made available through an EUA or through a traditional approval, FDA will ensure that it is safe and effective.”
In the roughly 1,000-word piece, Marks promised that an EUA decision will not be rushed. And he explained that the FDA’s minimum recommendation of 50% efficacy is just that — a minimum.
“Of course, it is hoped that the vaccines will prevent a much higher percentage of cases, but the 50% figure establishes the minimum efficacy of a COVID-19 vaccine that FDA could find acceptable,” he said.
The director also mentioned that considerations for an EUA may be different, depending on how a product will be used. For example, if a drug is intended for hospitalized patients who have no other treatment, “the potential benefits may outweigh the risks even if there is uncertainty about effectiveness and there are real, but acceptable, safety concerns,” Marks wrote.
In June, the FDA yanked an EUA for hydroxychloroquine as a Covid-19 treatment, after determining the drug is “unlikely to be effective.” And in September, a panel of experts convened by the NIH concluded that there is a lack of data supporting the safety and efficacy of another coronavirus treatment granted an EUA: convalescent plasma.
In the op-ed, Marks said that wouldn’t be the case for a vaccine:
For a COVID-19 vaccine that could be administered to millions of individuals, including healthy people, FDA will only issue an EUA if a vaccine has demonstrated clear and compelling efficacy in a large well-designed phase 3 clinical trial, much like would be required for a BLA.
Normally, drug makers take months to analyze data before submitting a BLA, which can be tens of thousands of pages long, according to Marks. “But these are not ‘normal’ times,” he said. “In the United States, we have seen many hundreds of people die every day from COVID-19.”
“With high uptake, COVID-19 vaccines have the potential to save many lives in the United States that may otherwise be lost. And saving as many lives as is possible must be the goal that we strive to achieve together,” he wrote. — Nicole DeFeudis
Sanofi and GSK pledge 200 million vaccine doses
Sanofi and GSK have agreed to give 200 million doses of their vaccine candidate to the COVAX Facility, which is part of a program set up by CEPI, the WHO and Gavi to equitably distribute vaccines around the world.
The idea behind COVAX is to give all participating countries equal access to vaccines, regardless of income level. As of Oct. 14, more than 180 countries had signed agreements to the COVAX Facility, including France and the UK. China joined earlier this month, pledging to make its vaccines a “global public good.” One country notably off the list is the United States.
The Trump administration has refused to join the program. The US has placed an initial $1.95 billion order for 100 million doses of Pfizer’s candidate, with the option to acquire up to 500 million more down the road. And it placed a $1.5 billion order with Moderna for 100 million doses, with an option for another 400 million later. One White House spokesman said the country won’t be “constrained by multilateral organizations influenced by the corrupt World Health Organization and China,” according to a Bloomberg report.
COVAX is hoping to have 2 billion doses available by the end of 2021, “which should be enough to protect high risk and vulnerable people, as well as frontline healthcare workers,” the GAVI website states.
Sanofi and GSK entered their adjuvanted recombinant protein-based candidate in a Phase I/II study on Sept. 3, and anticipate the first cut of data in early December. The companies are hoping the results support the launch a pivotal Phase III trial before the end of the year. If all goes according to plan, they think a request for approval could come in the first half of 2021.
“The commitment we are announcing today for the COVAX Facility can help us together stand a better chance of bringing the pandemic under control,” Sanofi Pasteur executive VP and global head Thomas Triomphe said in a statement. “This moment also reflects our long-term commitment to global health and ensures our COVID-19 vaccines are affordable and accessible to those most at risk, everywhere in the world.” — Nicole DeFeudis
Vaccinologist Paul Offit calls for more efficacy data
In the next couple months, drug makers will likely submit EUA applications for Covid-19 vaccines, renowned vaccinologist Paul Offit predicts.
This could come at the beginning of a “twindemic” — parallel flu and coronavirus outbreaks, he added. The question is, what will be required for emergency authorization?
“Permission is being given to vaccinate 150 million Americans essentially, which is obviously something we’ve never dealt with before,” Offit, director of the Children’s Hospital of Philadelphia’s Vaccine Education Center and inventor of the rotavirus vaccine, said in a JAMA Network interview.
“How much uncertainty are we willing to live with knowing that we’re facing a virus that’s brought us to our knees?” he asked later.
Offit said he’s concerned the public will see emergency authorization as “flimsy,” or based on a lack of evidence, after what happened with hydroxychloroquine and the “convalescent plasma fiasco.”
“I think where the rubber’s going to meet the road here is how we handle these interim analyses,” he said in the interview.
Pfizer and BioNTech, currently in the lead for an EUA, announced in their trial protocol that their first interim analysis would occur when 32 participants are infected. Moderna will hold its first interim analysis at 53 events. And AstraZeneca is planning to conduct an analysis when 75 patients get sick. Researchers would then compare how many infections occurred in the vaccine arm, versus the placebo arm.
“I’d like to think that we’re going to be really loathe to approve this or to recommend approval through emergency use authorization with just 34 or 60 participants getting sick,” Offit said.
In NIH ACTIV trials, statisticians wanted to see 147 infections if the vaccine was administered in a 2:1 ratio to placebo, or 160 infections in a 1:1 scenario, Offit said. “That’s where I’m coming from,” he added.
“If dreams could come true, all I ask is this: Let’s have at least 150 participants that got sick,” Offit said. “That’s all I ask.” — Nicole DeFeudis