ACTT releases Remdesivir report, advancement of Moderna vaccine, and new combination therapies being tested

In exciting news, the official report of the ACTT trial for Remdesivir was published in the New England Journal of Medicine this week (Beigel JH, et al.). In the study, we saw an expansion of the previously released preliminary results with stronger significance for the efficacy of Remdesivir on reducing time to recovery in a subset of hospitalized patients (those who require  oxygen and ongoing care, but no ventilation). It is interesting that patients in the ICU did not respond well to the therapy, potentially  due to close timing of therapy in relation to peak viral load. Although this trial has ended, its successor, the ACTT-2 trial, will still include Remdesivir as a therapy and compare it against a placebo group and a joint therapy of Remdesivir with Barciticinib, a anti-inflammatory JAK inhibitor. 

The World Health Organization announced on May 27th that hydroxychloroquine clinical studies under its SOLIDARITY trial would be temporarily stopped following results demonstrating a lack of efficacy for the drug. As a large multinational trial, hopefully SOLIDARITY will begin releasing preliminary results soon to help guide treatment. This trial is also of particular interest as therapies including Lopinavir, Ritonavir, and Interferon beta-1a are not under heavy consideration in the US. Of note, the United States has announced a termination of funding and support to the World Health Organization at this time, further polarizing clinical trials.

Furthermore, there has been a lot of excitement around the Moderna vaccine trial, an mRNA vaccine of the Spike protein. With the initial success of the phase I trial, phase II is underway with phase III trials planned for early July. Moving forward a modified dosage scheme will be used to minimize the risk of adverse events observed at the high dose in phase I. However, with all three dosage schemes of vaccine in phase I, Moderna reported successful development of neutralizing antibodies by day 43 post vaccination.

Finally, Roche and Gilead announced a new trial (REMDACT) combining Remdesivir with Tocilizumab, an anti-IL6 monoclonal antibody. This trial has a similar structure to the ACTT-II trial, in which an anti-inflammatory therapy is combined with the antiviral properties of Remdsivir to address both the cytokine storm and virus in COVID-19. Roche also announced that their stand alone trial of Tocilizumab (COVACTA, NCT04320615) is nearing completion, which holds a large amount of promise in treating the IL-6 cytokine storm.