PTC Therapeutics Initiating Phase 2/3 Trial for COVID-19 Investigational Therapy

New Jersey-based PTC Therapeutics announced this week it is entering a phase 2/3 trial for its investigational therapy, PTC299, for the treatment of patients with coronavirus 2019 (COVID-19).

The oral medication is a novel dual-mechanism agent designed to treat viral replication and uncontrolled inflammatory response.

This trial is a randomized, double-blind, placebo-controlled, multi-national study. There will be 2 stages initiating in the US, and plans to conduct research among patients in Spain, Brazil, and Australia.

According to the company, the oral, small molecule tablet inhibits the dihydroorotate dehydrogenase (DHODH) cellular enzyme, which is used to produce the RNA building blocks for the production of SARS-CoV-2.

In addition, the investigational molecule has previously demonstrated potent inhibition of viral replication in SARS-CoV-2 cell based assays. A number of RNA viruses require the same building blocks, which explains why in preclinical tests PTC299 has shown broad spectrum antiviral activity.

“We are excited about the potential of PTC299 to be part of the solution to this unprecedented global public health crisis and have made it a high priority within our organization,” said Stuart Peltz, PhD, chief executive officer PTC Therapeutics. "The fact that PTC299 inhibits DHODH uniquely addresses the two key issues of COVID-19, namely reducing the high viral replication and also selectively attenuating the immune response caused by the uncontrolled cytokine storm resulting from the SARS-CoV-2 infection."

The study will be done in 2 stages starting with 40 enrolled patients in the first, and a larger cohort of approximately 340 participants. The company’s primary objective is to evaluate the clinical efficacy of PTC299 compared with placebo assessed by time to respiratory improvement in adult individuals hospitalized with COVID-19.

“In the lab, it has already been used in people, it is already formulated as a tablet, and it may attenuate the deadly inflammation observed in the most severe cases of COVID-19,” said Dr. Jeremy Luban, Professor, University of Massachusetts Medical School. “Additionally, PTC299 targets a cellular enzyme, as opposed to a viral one, and is therefore less likely to elicit drug-resistant SARS-CoV-2."

Along with the COVID-19 indication, the company is also looking into developing the investigational therapy for oncology treatment and acute myeloid leukemia.