- An independent committee overseeing clinical trials of Regeneron's experimental COVID-19 drug has told the company to pause enrollment of some hospitalized patients in one late-stage study.
- The committee found a "potential safety signal and an unfavorable risk/benefit profile" and recommended Regeneron stop recruiting patients who need high-flow oxygen or mechanical ventilation, pending data from those already enrolled. Regeneron is clear to continue testing the drug in people who need less or no breathing support, as the benefit-to-risk ratio "remains acceptable." Outpatient studies can continue unchanged as well.
- Regeneron's drug is one of two antibody-based COVID-19 treatments under review for emergency clearance in the U.S. While Regeneron and Eli Lilly's medicine have shown potential to help patients with mild or moderate COVID-19, both companies have now had to pause trials in hospitalized patients. Investigators later determined Lilly's drug wasn't likely to help in those sicker patients.
Engineered antibody drugs, which mimic the body's immune response to viral infections, have been viewed as a potential "bridge" to a coronavirus vaccine. In theory, the drugs could potentially prevent infections from developing into COVID-19, stop disease progression or even help improve outcomes for those who are already very sick.
Four candidates are now in late-stage testing. The two furthest along, from Regeneron and Eli Lilly, could soon be cleared for emergency use by the Food and Drug Administration.
Data to date suggest Regeneron's and Lilly's drugs might alleviate symptoms more quickly, reduce medical visits or hospitalizations and help lower levels of virus in the body. If proven in further study, these medicines could be critical tools in easing the burden on the U.S. healthcare system at a time when COVID-19 cases are surging.
But the true benefit of antibody drugs remains unclear. And as more data has been accrued, their limitations have become more apparent, which could potentially impact the regulatory reviews now underway.
Study results from both companies indicate the antibody drugs are working best in subsets of patients with mild or moderate disease who have certain medical risk factors, such as certain pre-existing health conditions. The treatments have appeared less helpful for people in those groups whose immune systems are capable of mounting their own attack against the virus.
A study of outpatient treatment with Lilly's antibody bamlanivimab, published in the New England Journal of Medicine, found most patients, including those on placebo, cleared the virus after 11 days. Updated results from Regeneron, also in the outpatient setting, showed the company's drug reduced virus levels and COVID-19 related medical visits, but found no "robust associations" between treatment and symptom alleviation.
Friday's news from Regeneron raises further questions about the ability of antibody drugs to help COVID-19 patients who are already very sick. Lilly's drug, meanwhile, is no longer being used in a government-run trial in hospitalized patients. The study was paused in mid-October due to potential safety concerns, and though the study oversight committee didn't find a problem, investigators determined bamlanivimab wasn't helping patients.
Regeneron didn't specify the safety issue flagged by the trial monitoring board in its study of hospitalized patients. Testing will continue in just two of the four study groups: those who don't need breathing support, or if they do, only low-flow oxygen.
The company said it has informed the FDA of its findings, as well as the investigators overseeing the large RECOVERY trial in the U.K., which is also testing Regeneron's drug in hospitalized patients.
COVID-19 antibody drugs could be more helpful earlier in the course of disease, when treatment can prevent the virus from infecting cells and replicating. Regeneron has studies underway testing its antibody treatment in people who have been exposed to infected household contacts and in those with mild or moderate disease.
But the preventive trial isn't expected to produce results until next June, according to the clinicaltrials.gov database. And given Regeneron's limited supplies, the need for treatment before disease progression, and the logistical hurdles of administering an infused treatment, getting the drug to the right patients when they need it would be a challenge.
AstraZeneca and partners Vir Biotechnology and GlaxoSmithKline also have antibody drugs in late-stage testing. Neither have disclosed efficacy data yet.
Regeneron shares fell about 4% during Friday trading.