Interferon, Favirpiravir, and Tocilizumab Preliminary Data Shows Potential in COVID-19 Treatment

This past week a lot of exciting announcements came from trials testing novel therapies for COVID-19. First, in a recent press release, Synairgen reported on their interferon beta-1b phase II trial (n=220, 120 out patients and 100 in patients) in which patients on interferon beta therapy were more than twice as likely to recover (p=0.043) and were significantly less likely to develop severe disease by 79% (p=0.046). In addition, the measure of breathlessness was notably reduced in patients treated with interferons (p=0.007). However it is important to remember that this is still a small trial that will need to be further substantiated with additional data or trials. Nevertheless, with these being some of the best results reported so far in the COVID literature, it will be exciting to see what other interferon trials (such as SOLIDARITY) find, and how different interferons compare in efficacy. 

Following the increased production of favirpiravir (FabiFlu), India has announced results of their Phase III trial (n=150), in which favirpiravir therapy results in a 40% faster time to recovery. At this time, there was no significant reduction in mortality. With this trial still containing a low number of participants, it will be critical to see what larger studies find as how these results compare to trials underway in US and Japan.

Tocilizumab (an anti-IL6 monoclonal antibody) rapidly entered clinical trials following the reported association between COVID-19’s cytokine storm and circulating levels of IL-6. A recent study of Tocilizumab therapy reported a 45% reduction in mortality when this therapy was used to treat severe COVID-19 patients (Somers EC, et al., 2020). However, the study found Tocilizumab therapy was also associated with an increased predisposition to superinfections in the severe COVID-19 patients. Within both groups, patients with superinfections did not demonstrate a higher mortality rate. Previously, a retrospective study noted a protective effect of Tocilizumab as shown in Figure 1, but did not report the higher risk of superinfections (Guaraldi G, et al., 2020).

It is exciting that Interferon-b, Favirpiravir, and Tocilizumab all show great promise but larger trials will be required to validate these initial findings and reveal how disease severities, comorbidities, and timing of treatment administration will affect efficacy of each of the therapies. Of note both interferons and Tocilizumab will be of interest to continue watching due to their unique hypothesized mechanism of action in COVID-19. Like Remdesivir, interferons are antivirals; however, interferons are natural proteins (with some manufactured versions being recombinant) which “interfere” with viral replication earning them their name of interferons. Interferons are thus a prime candidate for most viral infections as they have many pleiotropic effects through direct communication with the immune system to help fight viruses (Maguire C, et al. 2020). On the other hand, Tocilizumab, an anti-IL6 antibody, can reduce inflammation by binding and suppressing the inflammatory cytokine IL-6. This therapy is primarily being studied in severe patients with cytokine storm which has devastating systemic effects from an “overactive” immune system. By suppressing IL-6, patients with late-stage critical disease might have better survival outcomes.