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Why Kevzara Might Reduce Deaths from COVID-19

Kevzara (sarilumab) was developed by Regeneron and Sanofi as a human monoclonal antibody against the interleukin-6 (IL-6) receptor. It was initially approved for the treatment of rheumatoid arthritis (RA) in the US in May 2017 and the EU in June 2017. IL-6 a powerful pro-inflammatory cytokine that when over produced by the body’s immune system can lead to tissue damage which is the case in RA. By blocking the IL-6 receptor, Kevzara can be effective in treating RA. There is compelling evidence that over-production of IL-6 is a major cause of death in COVID-19 patients so that this IL-6 blocking mechanism of action may be able to reduce mortality. Most deaths from COVID-19 result from Adult Respiratory Distress (ARDS) that follows the viral infection and is caused by over-production of IL-6.

ARDS causes fluid buildup in the alveoli (tiny, elastic air sacs) in the lungs. The fluid keeps the lungs from filling with enough air, which reduces the amount of oxygen reaching the bloodstream. This deprives bodily organs of the oxygen they need to function resulting in life threatening breakdowns of organ systems. ARDS typically occurs in people who are already critically ill or who have significant injuries. Severe shortness of breath — the main symptom of ARDS — usually develops within a few hours to a few days after the precipitating injury or infection. Many people who develop ARDS don't survive. The risk of death increases with age and severity of illness. Of the people who do survive ARDS, some recover completely while others experience lasting damage to their lungs.

In addition to a theoretical argument that blocking IL-6 may treat or prevent ARDS, there is preliminary evidence in humans suggesting activity. In a single-arm, 20-patient Chinese trial in severely ill COVID-19 patients, most experienced rapidly reduced fevers and 75% of patients (15 out of 20) reduced their need for supplemental oxygen within days of receiving a different IL-6 receptor antibody (tocilizumab). Based on these results, China recently updated its COVID-19 treatment guidelines and approved the use of tocilizumab to treat patients with severe or critical disease.

A Clinical Trial of Kevzara in Severe COVID-19 Infections Is Underway

Regeneron announced today that it has started a clinical program evaluating Kevzara in patients hospitalized with severe COVID-19 infection.  This trial will begin at medical centers in New York, one of the epicenters of the outbreak, and will assess the safety and efficacy of adding Kevzara to usual supportive care, compared to supportive care plus placebo. The multi-center, double-blind, Phase 2/3 trial has an adaptive design with two parts and is anticipated to enroll up to 400 patients. The first part will recruit patients with severe COVID-19 infections across approximately 16 U.S. sites, and will evaluate the impact of Kevzara on fever and patients' need for supplemental oxygen. The second, larger part of the trial will evaluate the improvement in longer-term outcomes including preventing death and reducing the need for mechanical ventilation, supplemental oxygen and/or hospitalization.

In the Phase 2 part of the trial, 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. The phase 2 findings will be utilized in an adaptive manner to determine transition into phase 3, helping to determine the endpoints, patient numbers and doses. The second, larger part of the trial will evaluate the improvement in longer-term outcomes including preventing death and reducing the need for mechanical ventilation, supplemental oxygen and/or hospitalization.

Key Takeaways

This seems to be an extremely hopeful development for reducing the death rate from COVID-19. A vaccine against this virus will take more than a year to develop. Other drug approaches to treating COVID-19 are also in very early stages of development and we can only guess at their efficacy and safety. With Kevzara, we have a drug that is already approved so there is good reason to believe that it safe and importantly, there is the ability to manufacture the product in adequate amounts to treat most or perhaps all severely ill COVID-19 patients, if warranted.

Based on the latest statistics I have seen; the US so far has reported 3,774 cases and 69 deaths. New York state accounts for the majority of the cases and Washington state has the greatest number of reported deaths. I have seen other reports that suggest that about 10% to 15% of cases result in severe illness. This would mean that about 375 to 435 have occurred and have resulted in 69 deaths so far. While the number is likely to increase rapidly from this number, the clinical trial should be able to treat a meaningful percentage. Because the disease is more concentrated in New York, California and Washington, the clinical trial can be focused initially in hospitals in those areas, allowing for rapid enrollment. I would also think that if initial phase 2 results in the trial are encouraging, the FDA might allow Kevzara to be made widely available on a compassionate use basis throughout the US as was the case in China.

There is hope.