Regeneron Pharmaceuticals and Sanofi said today they have launched a Phase II/III clinical program in the U.S. evaluating the marketed arthritis drug Kevzara® (sarilumab) as a treatment for severe COVID-19 coronavirus infection in up to 400 patients.

Kevzara is an interleukin-6 (IL-6) receptor antagonist approved by the FDA in 2017 to treat adults with moderately to severely active rheumatoid arthritis who have had an inadequate response or intolerance to one or more disease-modifying antirheumatic drugs.

Regeneron and Sanofi reason that IL-6 may play a role in driving the overactive inflammatory response in the lungs of patients who are severely or critically ill with COVID-19.

The companies noted that a potential role of IL-6 is supported by preliminary data from a single-arm, 21-patient trial in China using another IL-6 receptor antibody, tocilizumab, which is under study by several companies for effectiveness against SARS-CoV-2—and is marketed in the U.S. as Actemra® by Genentech, a member of the Roche Group.

The non-peer reviewed results from the Chinese study showed that 15 of 20 COVID-19 patients treated with tocilizumab reduced their need for supplemental oxygen within days of receiving that treatment, and showed rapidly reduced fever. Based on these results, China recently updated its COVID-19 treatment guidelines, approving the use of tocilizumab to treat patients with severe or critical disease.

“Data from China suggest that the IL-6 pathway may play an important role in the overactive inflammatory response in the lungs of patients with COVID-19. Despite this encouraging finding, it’s imperative to conduct a properly designed, randomized trial to understand the true impact,” George D. Yancopoulos, MD, PhD, co-founder, president and chief scientific officer of Regeneron, said in a statement. “Our trial is the first controlled trial in the U.S. to evaluate the effect of IL-6 inhibition prospectively in COVID-19 patients.”

To launch the trial quickly, Yancopoulos added, Regeneron and Sanofi have worked closely with the FDA and the Biomedical Advanced Research and Development Authority (BARDA).

Launching in New York

The U.S.-based trial will begin at medical centers in New York, focused on assessing the safety and efficacy of adding Kevzara to usual supportive care, compared to supportive care plus placebo, in up to 400 adults hospitalized with serious complications from COVID-19. As of Sunday, New York City accounted for 329 of the 729 positive cases of COVID-19 reported across New York state, according to the state Department of Health’s daily novel coronavirus update.

The companies said their multi-center, double-blind trial has an adaptive design with two portions. In the Phase II portion, patients will be randomized 2:2:1 into three groups: Kevzara high dose, Kevzara low dose, and placebo. The primary endpoint is reduction of fever and the secondary endpoint is decreased need for supplemental oxygen.

Findings from the Phase II portion will determine which patients transition into Phase III, helping to determine the endpoints, patient numbers and doses. The Phase III portion will evaluate the improvement in longer-term outcomes including preventing death and reducing the need for mechanical ventilation, supplemental oxygen and/or hospitalization, Regeneron and Sanofi said.

To enter the trial, patients must be hospitalized with laboratory-confirmed COVID-19 that is classified as severe or critical, or who are suffering from multi-organ dysfunction. All patients must have pneumonia and fever. After receiving the study dose, patients will be assessed for 60 days, or until hospital discharge or death.

Regeneron would lead clinical studies in the U.S., while Sanofi would do so overseas.

More trials planned

“Additionally, we expect to rapidly initiate trials outside the U.S. in the coming weeks, including areas most affected by the pandemic such as Italy,” added John Reed, MD, PhD, Sanofi’s Global Head of Research and Development.

Italy has the second largest number of confirmed COVID-19 cases after China—24,747 as of Sunday at 11:33 p.m. ET, according to the Johns Hopkins Center for Systems Science and Engineering (CSSE) Coronavirus Resource Center.

Sanofi and Regeneron co-developed and co-market Kevzara. Later this quarter, the companies said, they expect to finalize a restructured collaboration for developing the drug—something they first said they would do in December 2019.

In addition to Kevzara, Reed added, Sanofi’s global business unit focused on vaccine development, Sanofi Pasteur, will build upon previous development work for a SARS vaccine as part of its effort to quickly develop a COVID-19 vaccine. That vaccine will be based on the company’s recombinant DNA platform, designed to produce an exact genetic match to proteins found on the surface of the virus.

Sanofi said the DNA sequence encoding the antigen will be combined into the DNA of the baculovirus expression platform and used for rapidly producing large quantities of the coronavirus antigen, which will be formulated to stimulate the immune system to protect against the virus.

Regeneron also has its own COVID-19 therapy development effort, focused on combining REGN3048 and REGN3051. The neutralizing monoclonal antibodies leverage Regeneron’s monoclonal antibody discovery platform called VelocImmune®, part of the company’s VelociSuite™ technologies. Regeneron hopes to have the combination therapy available for human testing this summer, Yancopoulos added.

REGN3048/REGN3051 and the Sanofi vaccine are two of the Top 35 Treatments in Development for COVID-19 that were highlighted in a recent GEN A-List.

Another treatment on that list, Moderna’s novel lipid nanoparticle (LNP)-encapsulated mRNA vaccine mRNA-1273, is the subject of a Phase I study for which the company is partnering with the NIH’s National Institute of Allergy and Infectious Diseases (NIAID).

The first patient in that trial is to be dosed with mRNA-1273 today, the Associated Press reported yesterday, based on an unnamed “government official” who spoke anonymously because the dosing had not been publicly announced.