As his firm unveiled early data with its spike protein-targeting COVID-19 therapy, Regeneron Pharmaceuticals Inc.’s chief scientific officer, George Yancopoulos, said that, even if researchers come up with a drug that works, coming up with efficient point-of-care diagnostics remains “a major societal imperative.”
His remarks came as the Tarrytown, N.Y.-based firm rolled out results from a descriptive analysis of the company’s trial of its antibody cocktail, REGN-COV2, which reduced viral load as well as the time taken to alleviate symptoms in non-hospitalized patients with COVID-19. Made of two virus-neutralizing monoclonal antibodies, REGN-10933 and REGN-10987, the compound also turned up positive trends in reducing medical visits. Specifically, REGN-COV2’s antibodies bind in a non-competitive way to the critical receptor domain of the virus's spike protein, which diminishes the ability of mutant viruses to escape treatment and protects against spike variants that have arisen. Randomized, double-blinded, the ongoing, seamless phase I/II/III experiment is designed to measure the effect of adding REGN-COV2 to standard-of-care treatment compared to adding placebo.
The analysis of the first cohort of 275 patients from the trial was meant to evaluate antiviral activity and identify patients most likely to benefit from REGN-COV2. In the placebo group, seropositive patients – those with measurable endogenous antibodies to COVID-19 – showed a median time to alleviation of symptoms of seven days vs. seronegative patients whose time was 13 days. Median time to symptom relief was 13 days with placebo, eight days in high dose (p=0.22), and six days in low dose (p=0.09). The proportion of patients with at least one COVID-19-related, medically attended visit through day 29 was five of 33 (15.2%) in placebo vs. two of 41 (4.9%, p=0.1370) in low dose (2.4 g) vs. three of 39 (7.7%, p=0.2723) in high dose (8 g). At the optimal dose (2.4 g given intravenously) and in the responsive patients (seronegative), REGN-COV2 reduced the rate of medical intervention by 68%, a rate similar to that recently reported by Indianapolis-based Eli Lilly and Co. with its antibody (72%), and SVB Leerink analyst Geoffrey Porges said in a report that the findings “should guide future treatments.” He called the treatment “moderately effective at reducing viral load,” with a “limited effect on the overall rate of progression to more severe disease (given a low event rate).” REGN-COV2 was safe and well-tolerated, Regeneron said.
Wainwright analyst Patrick Trucchio pointed out in a report that at baseline, 65% of patients had at least one risk factor for severe COVID-19 but patients “were relatively young,” at 44 years on average. “Moreover, there does not appear to be a dose response on clinically meaningful endpoints, at least in this data cut,” he wrote. Low-dose REGN-COV2 “could provide an additional treatment option in high viral-load patients,” in his view. “We look forward to an update on discussions with regulators.”
Regeneron “used very specific serological testing here that is not necessarily what will have to be used in the field to determine seropositivity,” Yancopoulos said during a conference call with investors. Many companies are working the diagnostic angle, he noted. “You don't have to necessarily look for serological status only; you can also just simply use high viral load because we showed the incredible correlation.”
Two papers in Science explained how the cocktail works. “It's not like we saw one trend or one thing going with viral clearance, and different thing with symptomatology or medically attended visits – it was all the same,” Yancopoulos said. “The benefit seemed to be the greatest in the patients who needed it the most.” He declined to speculate on the likelihood of an emergency use authorization. “We've already enrolled patients who will comprise a prospective replication cohort to provide a data package that we think would potentially support a full approval,” he said. “It’s up to regulators and society to decide whether or not this current package deserves to make this therapeutic intervention available sooner to patients who might need it.”
Oxford U. in the game, too
About a month ago, Paris-based Sanofi SA and Regeneron decided to end all further development in COVID-19 of their interleukin-6 receptor inhibitor, Kevzara (sarilumab), following the antibody’s failure to meet the primary endpoint, as well as a key survival endpoint, in an ex-U.S. trial in 420 hospitalized patients with severe or critical disease. July saw the failure of a Regeneron-sponsored U.S. phase III trial of the same drug in COVID-19 patients in need of mechanical ventilation.
Although Regeneron took most of the spotlight, others had COVID-19 news. Curevac AG, of Tubingen, Germany, dosed the first subject in its phase IIa trial with the vaccine known as CVnCoV. The dose-confirmation study, CV-NCOV-002, is being conducted in Peru and Panama and will enroll 690 healthy participants in two groups: adults ages 61 and above, and participants ages 18 to 60. All will get vaccinations at intervals of 28 days. Different dose levels will be investigated, starting at 6 µg. In a geographical environment with a high incidence of COVID-19 infection, the humoral immune response after administration of CVnCoV will be assessed and the safety database expanded to prepare for the start of a phase IIb/III study. First comprehensive data from phase IIa in older adults are expected later this year.
Cambridge, Mass.-based Moderna Inc. disclosed the publication of the second interim analysis of the open-label phase I study with mRNA-1273, its vaccine candidate, in The New England Journal of Medicine. That analysis evaluated a two-dose vaccination schedule of mRNA-1273 given 28 days apart in 40 healthy adult participants across two dose levels (25 µg and 100 µg) in two age cohorts (ages 56 to 70 and ages 71+), and includes results through day 57 (a month after the second dose). Both dose levels were generally well-tolerated in both age cohorts. Immune responses were dose-dependent, with the 100-µg dose eliciting higher binding and neutralizing antibody titers, supporting the selection of the 100-µg dose for further study in the phase III effort, Moderna said. The study was led by the NIH.
In the U.K., researchers at the University of Oxford are launching a study to test the anti-TNF drug Humira (adalimumab, Abbvie Inc.) as a treatment for COVID-19, with a focus on community care settings. The AVID-CC trial, which will be conducted by Oxford Clinical Trials Research Unit, is due to enroll up to 750 patients. Humira was first approved at the end of 2002 for rheumatoid arthritis.
Shares of Regeneron (NASDAQ:REGN) closed Sept. 30 at $559.78, down $13.83.