New data from the biotechnology firm Regeneron seem likely to add to the excitement about drugs called monoclonal antibodies as treatments for Covid-19, but experts caution more data will be needed to know how potentially beneficial the medicines are.
A high dose of the company’s antibody cocktail, REGN-COV2, led levels of the virus to decrease more quickly in infected, non-hospitalized patients, potentially indicating the treatment may help them get better, Regeneron reported Tuesday via press release. Full results will be published at a later date.
“There’s nothing bad about these results, you just can’t say much about how transformative this is going to be,” said Eric Topol, director of the Scripps Research Translational Institute. As with data from a similar antibody, developed by Eli Lilly, he warned that the data so far should not be enough for the Food and Drug Administration to grant an emergency use authorization.
“This doesn’t cut it, but it’s moving in the right direction, that’s for sure,” Topol said.
In a notable finding, the data seem to show that the antibody had a bigger effect in patients who tested positive for SARS-CoV-2 but had not created high levels of their own antibodies against the virus. In this group, even a lower dose of the Regeneron antibodies seemed to result in patients getting better faster.
The data add to the early results from Eli Lilly, which showed a reduction in virus levels for patients at some doses and a tantalizing hint that the treatment might help keep patients out of the hospital.
Monoclonal antibodies are synthetic versions of one of the immune system’s own weapons against invaders. From the start of the pandemic, some experts have been most hopeful about this technology to create new medicines to fight SARS-CoV-2, the virus that causes Covid-19. But that potential could be limited by the ability to manufacture large quantities of the treatments. Regeneron has reached an agreement with Roche, the Swiss drug giant, to increase its production capacity.
Experts said longer studies, which are ongoing, will be needed to really know if the antibody treatments make patients better.
“We are highly encouraged by the robust and consistent nature of these initial data, as well as the emerging well-tolerated safety profile, and we have begun discussing our findings with regulatory authorities while continuing our ongoing trials,” said George Yancopoulos, Regeneron’s chief scientific officer.
The data are from a 275-patient portion of Regeneron’s study testing REGN-COV2 in patients who have tested positive for Covid-19 but who are not in the hospital.
Patients received either placebo, 2.4 grams of REGN-COV2, or 8 grams of REGN-COV2. (The antibody cocktail is delivered intravenously.)
Those who received the high dose saw viral levels decrease by 0.60 log10 copies of the virus per milliliter compared to placebo after seven days, a result that was statistically significant. In the lower dose, there was a 0.23 log10 reduction, which was not statistically significant. Regeneron did not give the total amount of virus detected in its press release.
At the beginning of the study, Regeneron tested patients not only to see if they had SARS-CoV-2, but also to see if they created their own antibodies against the virus. The company found that 45% of patients had created antibodies, 41% had not, and 14% had unclear results.
Those without antibodies had higher levels of virus in swabs from their noses from the start. And those who had created their own antibodies got better much faster. Patients with their own antibodies in the placebo group saw symptoms disappear in seven days, while in those whom antibodies were not detected, it took 13 days for symptoms to go away.
Giving the patients Regeneron’s synthetic antibody had a far greater effect on the amount of virus detected in those who did not have an antibody response before treatment. There was a reduction of 0.6 log10 copies/mL in the patients who received the high dose, and 0.51 in those who received the low dose, both of them statistically significant.
The reductions were also greater in patients who had higher levels of virus. And in those patients who did not have detectable antibodies at the study’s outset, Regeneron’s antibody cocktail improved symptoms. In this group, symptoms were alleviated in 13 days on placebo, eight days in the high-dose group, and six days in the low-dose group.
Among the 275 patients for whom data are being reported, 50% were Hispanic, 14% were African American, and the rest of the racial breakdown was not disclosed. On average, they were 45 years old. Forty-nine percent of participants were male and 51% were female.
A second portion of the study will recruit 1,300 patients, who will be followed for 29 days, with virus levels in the upper respiratory tract tested every two to three days and clinical endpoints assessed by doctors running the study and patients themselves.
Regeneron’s antibody cocktail is also being treated in hospitalized patients in the U.K. RECOVERY trial, which has yielded several important results about what medicines do and don’t work against Covid-19, and in a study to see if it can prevent household contacts of infected people from becoming infected.
Nahid Bhadelia, the medical director of the Special Pathogens Unit at Boston Medical Center, said that the results indicate it may be useful to test patients’ antibody response to identify those who may be headed toward worse clinical outcomes. “This is not currently done,” she wrote in an email to STAT, but there could be a place for it if the large study pans out.
“We have made advances in reducing mortality in hospitalized patients, but we haven’t found anything yet that decreases chances of hospitalization in the first place,” Bhadelia wrote.
What she needs to see now, she said, are results on hospitalization, disease worsening, and mortality in the ongoing larger study.
On a conference call after the data were released, Yancopoulos said that the “consistent picture” provided by the data meant that it should be considered by the FDA.
“I think it deserves to be discussed with the regulatory authorities because of all of the societal implications,” he said. “And I think it’s not up to us. I mean, you know, we’re not going to be the arbiter on this. We think that there is a lot of evidence here to suggest that this is a therapeutic solution that could really benefit quite a number of individuals and patients.”
If the FDA were to clear the antibody, would Regeneron be able to make enough? Could a testing regimen be implemented on the fly?
“This is something that we as a society are going to have to grapple with: How to utilize a potentially powerful weapon in the most powerful way to control and fight back against this pandemic,” Yancopoulos said.