Sarilumab, Lopinavir/Ritonavir, and mRNA Vaccines in COVID-19 Updates

This week, the United Kingdom’s RECOVERY trial had a press release on the preliminary findings on the antiviral combo therapy of lopinavir and ritonavir, which is commonly used to treat HIV. They reported no significant benefit (p=0.58) from the therapy with a high 28 day mortality for both the treatment (22.1%) and the usual care (21.3%). The RECOVERY trial is aiming to release more results in the coming weeks on the remaining therapies, and is moving at an astonishing rate with results from three different therapies released in less than a month.

Sarilumab, an anti-IL6 receptor monoclonal antibody, in Sanofi’s phase III clinical trial for COVID-19, was prematurely ended. The press release on this early termination reported that adverse events occurred in 80% of sarilumab and 77% of the control placebo groups with more frequent multi organ dysfunction syndrome (6% Sarilumab and 5% placebo). There were high hopes that this anti-inflammatory drug would help curb the IL-6 driven cytokine storm that occurs in severe and critical COVID-19 patients, but perhaps the anti-IL-6 antibodies will fare better than targeting the IL-6 receptor.

Pfizer and BioNTech are making great strides on their mRNA vaccine: BNT162b1. This vaccine is similar to Moderna’s except it specifically encodes the Receptor Binding Domain (RBD) of the SARS-CoV-2 spike protein. By eliciting an immune response against this region specifically, the antibodies might better neutralize the virus and prevent entry into cells. In their Phase I/II trial, Pfizer’s preliminary data reported SARS-CoV-2 neutralizing antibodies titers 1.8 to 2.8 times that of convalescent plasma antibodies from SARS-CoV-2 infected individuals. Moving forward, it will be interesting to see if Pfizer tests other dosing schemes for the vaccine outside the 2 dose model used so far and how these models will compare. Similarly, it will be interesting to compare different SARS-CoV-2 mRNA vaccines efficacies in relation to what they encode particularly between whole protein and specific region vaccines. Finally, the FDA released detailed outlines on the expectation and standards that SARS-CoV-2 vaccines will be required to meet to gain approval.