Drugs in development for Covid-19 generally fall into two categories: antivirals that go after the SARS-CoV-2 virus itself and anti-inflammatory agents that address the hyperactive immune system response associated with the most serious symptoms of the disease. Now, a company hopes that one of the drugs it is developing can do both.
South Plainfield, New Jersey-based PTC Therapeutics said Wednesday that it had received authorization from the Food and Drug Administration to start a Phase II/III study of PTC299 in Covid-19. The company said the drug, a dihydroporotate dehydrogenase (DHODH) inhibitor, has a dual mechanism of action that could address both viral replication and uncontrolled inflammatory response.
The drug is in a 39-patient Phase Ib study in relapsed and refractory acute myeloid leukemia that opened in October 2018, according to the ClinicalTrials.gov database. The primary completion date was late last month, and the estimated completion date is in November, though the study, which opened in October 2018, is listed as still recruiting patients. Other studies, in breast cancer, HIV-related Kaposi sarcoma and other cancers, have already completed or been terminated.
The company’s rationale for testing PTC299 in Covid-19 is that the DHODH enzyme, which the drug inhibits, is used to produce the RNA building blocks that enable SARS-CoV-2’s production, and cell-based assays have shown that the drug exhibits “potent” inhibition of the virus. The company also said the drug appears to modulate the immune response by attenuating the stress-induced cytokine storm. Cytokine storm, whereby the immune system produces an overabundance of inflammatory cytokines, has been blamed for the most severe symptoms of Covid-19, such as pneumonia and organ failure.
“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,” PTC CEO Stuart Peltz said in a statement.
The FDA has given emergency use authorization to one antiviral drug for SARS-CoV-2, Gilead Sciences’ remdesivir, while other antivirals as well as anti-inflammatory drugs are also in clinical development. On Tuesday, data from a Phase II/III study in the U.K. indicated that a common steroid drug, dexamethasone, appears to reduce the inflammatory symptoms of Covid-19 and improve survival.
A Deep-dive Into Specialty Pharma
A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.
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