NIH Uncertain about Convalescent Plasma, Sanofi’s anti-IL6 Receptor mAb phase III trials show no results, and AstraZeneca bring their Adenovirus vaccine to the US

Last week, there were several interesting updates on the front of COVID-19 clinical trials. The first one is a statement released by the NIH which expresses disapproval of the recent emergency use authorization (EUA) granted by the Food and Drug Administration for convalescent plasma. The NIH raised concerns about the lack of data, particularly from double blinded studies. At this point in time, many questions remain about the safety and efficacy of convalescent plasma, which the NIH believes should have prevented the release of the EUA. As a result, the NIH has recommended against using this treatment as standard of care until more data is made available.

The COVID-19 cytokine storm has been connected to several clinical complications and has been strongly correlated with the cytokine IL-6. As a result, many anti-IL-6 and anti-IL-6 receptor antibody therapies quickly began COVID-19 clinical trials. Unfortunately, many of these antibodies have performed underwhelmingly in phase III trials. Last week, Sanofi announced Kevzara’s (sarilumab, an anti-IL 6 receptor mAb) clinical trial would be terminated due to non-statistically significant results in the primary and secondary health outcomes of critical COVID-19 participants. Since several IL-6 antibody trials have reported similar findings, and now with more complex cytokine storm data available, perhaps other cytokine antibodies should be considered for clinical trials in the near future. 

AstraZeneca recently announced it would begin phase III trials for its AZD1222 adenovirus vector-based vaccine in the US. On the adenovirus vector, the full spike protein is expressed which generates a humoral and cellular immune response to the SARS-CoV-2 spike protein as well as the adenovirus vector. The trial will enroll 30,000 US based participants in addition to the ongoing phase III trials in Europe. Uniquely, they will enroll at a 2:1 ratio of vaccine:control with the control being a meningococcal bacterial vaccine rather than a placebo. Similar to SARS-CoV-2 mRNA vaccines, the AZD1222 vaccine is a two dose system with the doses separated by 4 weeks. AstraZeneca has previously released their phase I/II data in the Lancet which showed promising results (Folegatti PM, et al., 2020). This vaccine will be one of the few vaccines in phase III trials already in the US, and it will be interesting to see how the results compare to other vaccine systems such as the mRNA vaccines. 

Finally, the Sputnik-V vaccine out of Russia was one of the first to go public, although under intense scrutiny for skipping phase III trials. Recently the results from phases I and II of the vaccine were released in the Lancet (Logunov DY, et al., 2020). Overall, the results showed an antibody response comparable to convalescent plasma; however, the study failed to have placebos or controls, and had a very limited n of 76. In addition, the observed antibody titres were lower than those reported of other SARS-CoV-2 mRNA vaccines and the ChAdOx1 vaccine. Additional phases and further testing for this vaccine are occurring in several countries including Russia despite already being distributed in Russia.