A different IL-6–blocking monoclonal antibody, sarilumab, marketed in the US as Kevzara by Regeneron and Sanofi, has recently showed underwhelming results in treating severe, but not critically ill, COVID-19 patients in a randomized phase 2/3 clinical trial (ClinicalTrials.gov Identifier: NCT04315298).3 This has led to them modifying the study to continue looking at only the sickest patients.
There is also an adaptive phase 2/3 trial examining sarilumab in patients hospitalized with COVID-19 (ClinicalTrials.gov Identifier: NCT04327388). It is currently recruiting patients.
Dr Eisner said on April 27, 2020, that Genentech has no plans to make any amendments to its original trial, but the company does have interim analyses planned to quickly identify any evidence of efficacy associated with the use of Actemra for COVID-19.
Tocilizumab is approved for the treatment of CAR-T–related cytokine release syndrome and is also used for the treatment of both adult and juvenile rheumatoid arthritis. If tocilizumab or other similar monoclonal antibody drugs are shown to be effective in treating COVID-19, could there be a situation where the drug is at risk of shortage and could become unavailable for those with chronic arthritic conditions?
“This is not something that has concerned me so far; we are looking for hope. I’d love it if this would be the key agent which can transform outcomes for people with COVID-19. If it does work, pharma will have to address this and try to upscale their product,” said Dr Alvarnas.
Dr Cron seemed more worried about potential shortages, however. “That’s a concern, yes. Some of these companies may be more capable of ramping up than others. For the biologic drugs, in particular, these may be more difficult to ramp up. Colleagues are grabbing any of these drugs they can get; in the short-term it’s already an issue,” said Dr Cron.
Significant mortality and case numbers of COVID-19 patients in several countries where trials for CRS treatment are ongoing, combined with relatively short primary endpoints, could mean that many studies will be expected to produce results within weeks or months. For physicians and health care workers treating these critically ill patients, these results can’t come fast enough.
“Cytokine storms, in my opinion, are what is killing a large number of people, particularly younger people who have no preexisting conditions. In addition to trying to treat the virus, if the cytokine storm is present, you can’t ignore it — you must diagnose it and treat it. Hopefully the ongoing trials will tell us which therapies are effective for this,” said Dr Cron.
- Zhang X, Song K, Tong F, et al. First case of COVID-19 in a patient with multiple myeloma successfully treated with tocilizumab. Blood Adv. 2020;4(7):1307-1310.
- Ritchie AI, Singanayagam A. Immunosuppression for hyperinflammation in COVID-19: a double-edged sword? Lancet. 2020;395(10230):1111.
- Regeneron. Regeneron and Sanofi provide update on U.S. Phase 2/3 adaptive-designed trial of Kevzara® (sarilumab) in hospitalized COVID-19 patients. Published April 27, 2020. Accessed May 11, 2020.