This article summarizes the likely attenuation properties of
RRx-001 in
COVID-19 based on its mechanism of action and the putative pathogenesis of the disease, which appears to activate inflammatory, oxidative, and immune cascades with the potential to culminate in
acute respiratory distress syndrome,
cytokine storm and death. An ongoing pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2),
COVID-19 appears to present with 3 major patterns of clinical symptomatology: (1) mild
upper respiratory tract infection, (2) non-life-threatening
pneumonia, and (3) severe
pneumonia and
acute respiratory distress syndrome that initially manifest as a mild prodrome lasting for 7-8 days before rapid clinical and radiological deterioration requiring ICU transfer.
RRx-001 is a targeted
nitric oxide donor. This small molecule, which has been evaluated in multiple Phase 1-2 clinical trials for
cancer as well as a Phase 3 clinical trial for the treatment of
small cell lung cancer called REPLATINUM (NCT03699956), is minimally toxic and demonstrates clear evidence of antitumor activity. During the course of these clinical trials it was noted that the rate of
chronic obstructive pulmonary disease exacerbation and
pneumonia in actively smoking
small cell lung cancer patients treated with
RRx-001 is less than 1%. Due to extensive history of tobacco use, 40%-70% of patients with
lung cancer have
chronic obstructive pulmonary disease and the expected rate of pulmonary
infection in this population is 50%-70%, which was not observed in
RRx-001 clinical trials. Moreover, in preclinical studies of
pulmonary hypertension,
RRx-001 was found to be comparable with or more effective than the FDA approved agent,
Bosentan. The potential pulmonary protective effects of
RRx-001 in patients with recurrent lung
infections coupled with preclinical models demonstrating RRx-001-mediated reversal of
pulmonary hypertension suggests
RRx-001 may have therapeutic activity in patients with acute respiratory symptoms due to
COVID 19. Clinical trials have been initiated to confirm the hypothesis that
RRx-001 may be repurposed to treat
SARS-CoV-2 infection.