- An experimental coronavirus treatment from Eli Lilly and biotech partner AbCellera will no longer be used in a large, government-sponsored trial after an independent study committee found the antibody drug is not likely to help patients hospitalized with COVID-19.
- The committee met Monday to review data from the National Institute of Allergy and Infectious Diseases study known as ACTIV-3, which was halted two weeks ago due to potential safety concerns. Investigators didn't find a significant safety problem with Lilly's drug, but judged there to be a "low likelihood" that it would be "of clinical value." NIAID plans to file a report and continue the ACTIV-3 trial with a different experimental treatment.
- Lilly's drug, known as bamlanivimab, is one of two antibody-based COVID-19 treatments currently being evaluated by the Food and Drug Administration for an emergency clearance. But the agency's review of bamlanivimab appears complicated by manufacturing problems at a Lilly plant and the ACTIV-3 results.
Scientists and drugmakers face a daunting task. They're trying, in the middle of a pandemic, to develop treatments for a disease they're still trying to understand.
Seeking to speed the process, companies and government agencies have turned to "adaptive" trials that allow for more flexibility, as well as "master protocols" that help researchers simultaneously study multiple drugs. The goal is to quickly determine whether studies should be changed, if more or less participants are needed for the trial to return a result and whether drugs should be dropped from further study.
The ACTIV trials, run by NIAID via a partnership between 16 drugmakers and several government agencies, are playing a key role in this effort. Two of them are evaluating Lilly's antibody drug bamlanivimab alongside standard of care in patients who either are or aren't hospitalized. Both trials can be adapted to use different medicines if necessary.
Two weeks ago, a group of independent experts overseeing the hospitalized study, or ACTIV-3, recommended pausing enrollment after observing an "overall difference in clinical status" between the groups on Lilly's drug and placebo. When reconvening Monday and reviewing updated results, however, they recommended stopping treatment with bamlanivimab because the drug wasn't effective, rather than because of any safety problems.
"Differences in safety outcomes between the groups were not significant," NIAID said in a statement. The decision "was driven by lack of clinical benefit for [bamlanivimab] in a hospitalized population."
The result raises questions about the ability of antibody drugs, which work against the coronavirus itself, to help COVID-19 patients who are already very sick. In theory, these medicines should be more helpful earlier in the course of disease, when treatment can prevent the virus from infecting cells and replicating.
In its statement, Lilly noted the "advanced stage of the disease" of participants in ACTIV-3. All other studies of bamlanivimab that are enrolling mild or moderate COVID-19 patients are ongoing, including the NIAID study in non-hospitalized patients, dubbed ACTIV-2. Results from ACTIV-2 are expected next month, according to a presentation from Lilly Tuesday.
“While the results in hospitalized patients were disappointing, we don't expect this to affect our chances of success in prophylaxis or treatment,” said chief scientific officer Dan Skovronsky on a Tuesday conference call.
Study results to date have shown the potential for Lilly's and Regeneron's drugs to help those with mild or moderate COVID-19 shake their symptoms and clear out the virus. Each company has asked the FDA for emergency approvals based on that early data, which they're now trying to confirm with additional testing.
The drugs are newly in the spotlight, however, after Regeneron's was used to treat President Donald Trump and Lilly's was given to former New Jersey Gov. Chris Christie.
Regeneron believes its treatment may be best suited for those who don't mount an effective immune response to coronavirus infection, while Lilly is looking at risk factors like age or weight to guide treatment. Both will need to work with the FDA to define which patients would be included in those groups.
Regeneron has one late-stage study underway in hospitalized COVID-19 patients.
Lilly developed bamlanivimab through a collaboration with the privately held biotech AbCellera. Another antibody drug, developed with China's Junshi Biosciences, is being studied in combination with bamlanivimab. Lilly could seek emergency authorization of the combination regimen “as early as November,” Skovronksy said.
Both EUA requests could be impacted by “data handling” issues the FDA flagged at one of the facilities making Lilly’s COVID-19 antibody drugs. Lilly recently hired a consultant to conduct a review of the New Jersey plant and is incorporating suggested improvements to the site, according to CEO David Ricks.
“We are confident in the material at this facility, and frankly at all of our sites,” Ricks said on the conference call.
The agency is also reviewing a request to clear use of Lilly’s anti-inflammatory drug Olumiant in hospitalized COVID-19 patients, following positive results in a NIH-sponsored study testing the treatment alongside Gilead’s Veklury.
Lilly expects to invest $400 million on COVID-19 treatments this year.
Editor's note: This story has been updated with comments from a conference call.