Heading off hypoxia?

CHARLOTTESVILLE, Va.—Diffusion Pharmaceuticals Inc. has reported that the U.S. Food and Drug Administration (FDA) is accelerating its review of Diffusion’s clinical development plan using trans sodium crocetinate (TSC) in COVID-19 patients displaying severe respiratory symptoms and low oxygen levels.

Development of acute respiratory distress syndrome (ARDS) is common in patients hospitalized with COVID-19, due to a lack of sufficient oxygen to vital organs as a consequence of lung impedance. Diffusion believes that trans sodium crocetinate’s novel oxygen-enhancing mechanism of action could provide a new treatment option for this life-threatening condition.

Under federal regulations the FDA has up to 60 days to respond to Diffusions’s April 24 submission, but the FDA has announced its intention to significantly shorten review times for select COVID-19 submissions under its Coronavirus Treatment Acceleration Program (CTAP). Diffusion is continuing clinical trial preparations at multiple potential sites, as the company waits for the FDA’s expedited response.

Diffusion’s COVID-19 program is a cooperative research effort with the University of Virginia Health System and the Integrated Translational Research Institute of Virginia. The research program is meant to develop TSC as a treatment for ARDS from COVID-19, specifically targeting the associated multiple organ failure. To aid in timely trial enrollment, Diffusion is in discussions with institutions located in areas of severe COVID-19 incidence, both in the U.S. and in Eastern Europe.

“This news of accelerated FDA review of the proposed clinical development plan for our lead compound TSC in a COVID-19 ARDS program is most welcome,” said David Kalergis, chief executive officer of Diffusion. “We continue to work with hospital and regulatory authorities in the U.S., and now also in Eastern Europe, to forge the fastest possible pathway to approval for TSC in the treatment of COVID-19 patients.”

Like the FDA’s CTAP, health authorities in certain Eastern European countries have implemented emergency policies to compress regulatory review cycles from months to just days. These policies could expedite partnering possibilities with Eastern European national institutes that are currently treating hundreds of COVID-19 patients each day, with almost immediate study start up and shortened time to data.

Diffusion’s TSC was originally developed in conjunction with the Office of Naval Research, which was seeking a way to treat multiple organ failure caused by systemic hypoxemia from blood loss on the battlefield. Diffusion’s focus has expanded to multiple organ failure, stroke and glioblastoma multiforme, as well as ARDS due to COVID-19. In each of these diseases, hypoxia is the target for TSC’s novel mechanism.

In July 2019, Diffusion reported favorable safety data in a 19-patient dose-escalation run-in study to its Phase 3 INTACT program, using TSC to target inoperable GBM. Further findings from the study, released in December 2019, also showed possible signals of enhanced survival and patient performance.

Preclinical data supports the potential for TSC as a treatment for other conditions where hypoxia plays a major role, such as myocardial infarction, peripheral artery disease and neurodegenerative conditions like Alzheimer’s and Parkinson’s.