- A large government-run trial testing Eli Lilly's experimental COVID-19 antibody drug has been paused "out of an abundance of caution" while an independent study committee reviews safety data, the company confirmed Tuesday.
- The trial, sponsored by the National Institute of Allergy and Infectious Diseases, is studying Lilly's antibody drug in combination with Gilead's antiviral medicine Veklury as a treatment for patients hospitalized with COVID-19. Enrollment began in August.
- Lilly didn't disclose any further details, nor did an email reportedly sent by government researchers Tuesday morning. But researchers are on high alert for such safety issues, particularly after Johnson & Johnson this week halted vaccinations in studies of its experimental coronavirus shot due to an unexplained illness in one trial volunteer.
Just last week, Lilly announced it was asking the Food and Drug Administration for emergency clearance of its antibody drug, revealing new study results that suggest treatment may reduce the risk of hospitalization in people recently diagnosed with COVID-19.
Those data were from a Phase 2 trial run by Lilly, rather than the NIAID study in already hospitalized patients that's now on pause. Lilly and the U.S. government are working together to test the company's drug in several treatment settings.
The NIAID study, known as ACTIV-3, was designed to first test whether Lilly's drug appears safe and effective in 300 participants five days after treatment. If so, a second stage begins and another 700 participants are enrolled. So far, 326 patients have been enrolled, according to a NIAID spokesperson.
The trial pause was recommended by a data safety monitoring board, which is made up of independent experts and tasked with overseeing the study. While researchers and the company are "blinded" to the study data and whether participants received treatment or placebo, the DSMB can review unblinded results to assess potential safety risks.
On Tuesday morning, the DSMB found an "overall difference in clinical status" between the group receiving Lilly’s drug and those on a placebo, and recommended pausing enrollment, according to a NIAID spokesperson. The board will meet to review the data on Oct. 26 and decide whether or not the study should be resumed, the spokesperson said.
"Lilly is supportive of the decision by the independent DSMB to cautiously ensure the safety of the patients participating in this study," a company spokesperson said in an emailed statement. Lilly confirmed no other trial of its drug has been halted, and NIAID said no changes are being recommended to ACTIV-2, the other U.S. government-backed study of Lilly's drug.
Such safety reviews are relatively commonplace in large trials, and reflect appropriate management of the uncertainty that comes with testing experimental, unproven drugs. While the NIH's statement suggests the group receiving Lilly's drug and Gilead's Veklury appeared to be faring worse, it's not clear on what measure, nor whether the difference is directly attributable to treatment.
Veklury is authorized for emergency use in the U.S. and has been used relatively widely. But the drug has its own risks, and European regulators are currently reviewing its effects on the kidney.
Antibody treatments are newly in the spotlight after President Donald Trump was treated for COVID-19 with a similar drug developed by Regeneron. The New York biotech has also requested an emergency authorization from the FDA.
The drugs, which are synthesized to mimic the coronavirus-fighting antibodies found in recovered COVID-19 patients, could be an important tool in curtailing the worst effects of the pandemic, at least until an effective vaccine is found.
Yet it’s unclear how broad of a reach they’ll have. So far, Eli Lilly's and Regeneron’s drugs have shown the potential to help those with mild or moderate COVID-19 more quickly shake their symptoms and clear out the virus. With their requests for emergency clearances, both companies are targeting narrower groups of people most likely to benefit. Studies have not yet shown the drugs can help hospitalized patients.
Supplies of each are also likely to be limited until next year. Regeneron expects to produce about 300,000 doses by the end of the year, while Lilly said it could supply about 1 million before 2021.
Prior to human testing, the most significant safety concern cited by experts was the potential for antibody drugs to exacerbate COVID-19, as had been seen in past research of antibodies targeting other coronaviruses.
But up until this point, none of the COVID-19 antibodies in development have encountered any major safety problems. More than 850 patients, for example, have so far received either a one- or two-drug combination of Lilly’s antibody treatments in the four different trials already underway. Lilly has reported generally mild side effects, such as drug-related infusion reactions or hypersensitivity.
Though Lilly and Regeneron's antibody drugs are the furthest along, others from AstraZeneca and partners Vir Biotechnology and GlaxoSmithKline are also in late-stage testing. Several other companies, among them Amgen, Adagio Therapeutics and AbbVie, are also in the mix.
In some respects, antibody drugs work similarly to vaccines, making the safety review in the NIH trial potentially more worrisome if linked to Lilly's antibody. The review follows study halts for two leading vaccines from AstraZeneca and J&J. A U.S. trial of AstraZeneca's shot remains on hold following an unexplained illness in one volunteer in the U.K., although studies in other countries have resumed.
Editor's note: This story has been updated with comments from a NIAID spokesperson.