The U.S. Food and Drug Administration is wrapping up 2019 with a few PDUFA dates. Here’s a look.
The U.S. Food and Drug Administration (FDA) is wrapping up 2019 with a few PDUFA dates. Here’s a look.
Correvio Pharma’s Brinavess for Atrial Afibrillation
Correvio Pharma Corp., based in Vancouver, British Columbia, has a target action date of December 24, 2019 for its resubmitted New Drug Application (NDA) for Brinavess (vernakalant hydrochloride, IV). This is an antiarrhythmia drug for the rapid conversion of recent onset atrial fibrillation (AF) to sinus rhythm in adults.
The NDA was built on data from SPECTRUM, a post-authorization safety study conducted in Europe of 1,778 unique patients across a total of 2,009 treatment episodes after dosing of Brinavess. The data showed that Brinavess successfully converted 70.2% of the treated AF patients into normal sinus rhythm. It also demonstrated a median time to conversion of 11 minutes from the start of the first infusion in the patients who were successfully converted.
Brinavess is already approved for marketing in Europe, Canada and several other countries. It is approved in the EU for rapid conversion of recent onset atrial fibrillation to sinus rhythm in adults for non-surgery patients who had AF less than 7 days duration, for post-cardiac surgery patients with AF less than 3 days duration. It is not yet approved in the U.S.
On December 10, an FDA advisory committee met and voted 11 to 2 against recommending approval of Brinavess, citing safety concerns. The FDA is not required to follow the recommendations of its adcoms, but typically does.
Intra-Cellular Therapies’ Lumateperone for Schizophrenia
New York-based Intra-Cellular Therapies has a target action date of December 27 for its NDA for lumateperone for schizophrenia. This is actually three months after the initial PDUFA date after a planned submission of non-clinical data was viewed to be a major amendment to the NDA. The data was generated from toxicology data in animal studies. The company indicates that the metabolic pathway involved and the metabolites formed, are different in humans and animals and as a result, the animal findings are not relevant to humans.
Lumateperone selectively and simultaneously modulates serotonin, dopamine, and glutamate, three neurotransmitter pathways implicated in severe mental illness. It is a potent serotonin 5-HT2A receptor antagonist, a dopamine receptor phosphoprotein modulator (DPPM) acting as a presynaptic partial agonist and postsynaptic antagonist at dopamine D2 receptors, a dopamine D1 receptor-dependent indirect modulator of glutamate, and a serotonin reuptake inhibitor.
Amarin’s Vascepa For Reducing Heart Attack and Stroke Risk
Vascepa Corporation has a target action date of December 28 for its fish oil-based drug Vascepa (icosapent ethyl) for its supplemental NDA (sNDA) related to the REDUCE-IT cardiovascular outcomes trial. Currently, Vascepa is indicated as an adjunct to diet to reduce triglyceride (TG) levels in adults with severe hypertriglyceridemia.
On November 14, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) voted unanimously 16 to 0 to recommend approval of the drug for the indication and label expansion to reduce the risk of cardiovascular events in high-risk patients. This recommendation was based on results from the REDUCE-IT cardiovascular outcomes trial.
The agency is not required to go along with adcom recommendations, although they often do—particularly when they’re unanimous.
REDUCE-IT was a global CV outcomes trial that prospectively evaluated the effect of the drug in adults with LDL-C levels between 41 and 100 mg/dL that were controlled by statins and had various CV risk factors such as persistent elevated TG between 135-499 mg/dL and either established CV disease or diabetes, and at least one other CV risk factor. The trial ran for seven years and was completed in 2018. It tracked 8,179 patients at 400 clinical sites in 11 countries. The results were published in the journal Clinical Cardiology in March 2018 and subsequently the primary results were published in The New England Journal of Medicine in November 2018.
