In April, the U.S. Food and Drug Administration (FDA) issued a Refuse to File (RTF) letter to Zogenix for its New Drug Application (NDA) for Fintepla (fenfluramine hydrochloride).
In April, the U.S. Food and Drug Administration (FDA) issued a Refuse to File (RTF) letter to Zogenix for its New Drug Application (NDA) for Fintepla (fenfluramine hydrochloride). The drug was developed to treat seizures associated with Dravet syndrome, a rare form of epilepsy characterized by frequent and prolonged seizures.
The company at the time indicated the application, which was submitted in February, was not “sufficiently complete to permit a substantive review.” The FDA had two concerns, the first over non-clinical studies that were not submitted over chronic administration of the drug, and what Zogenix indicated as an incorrect version of a clinical dataset.
Today, the company announced that after its Type A meeting with the FDA on May 30, it plans to resubmit its NDA for Fintepla. Based on the meeting, the company will resubmit the NDA without the inclusion of the new chronic toxicity studies requested in the original RTF letter. In terms of the second issue, Zongenix ran a root cause analysis to explain the incorrect clinical dataset originally submitted and discussed that analysis with the agency.
“We are very pleased with the outcome of our meeting with the FDA and appreciate their thoughtful approach in considering the totality of the data from our drug development program, along with additional clinical and non-clinical literature that will be referenced in our resubmission,” stated Stephen J. Farr, president and chief executive officer of Zogenix. “We now have the clarity required to successfully resubmit our Fintepla NDA, which we will anticipate will occur in the third quarter.”
At the same time, although separate, the FDA rescinded its Breakthrough Therapy Designation for Fintepla for seizures associated with Dravet syndrome. The reasoning behind the decision is there are now two approved drugs for the disease, meaning the criteria for Breakthrough Therapy Designation has already been met.
In clinical data, Fintepla added to a stiripentol-based regimen resulted in a 54.7% greater decrease in mean monthly convulsive seizure frequency compared to patients who added a placebo to their stiripentol regimen. In other words, patients decreased the number of seizures they had by more than half.
The company stated, “However, no such comparisons were possible with cannabidiol (the second recently approved drug) since it was an investigational product at the time the Fintepla pivotal trials were conducted and was therefore an excluded treatment. Zogenix does not expect the rescission of Breakthrough Therapy Designation to limit the potential for Priority Review status (6-month review) for the Company’s resubmitted NDA.”
The drug they refer to is UK-based GW Pharmaceuticals’ Epidiolex (cannabidiol). It is marketed in the U.S. by its subsidiary Greenwich Biosciences. It was approved by the FDA on June 25, 2018. It is the first prescription formulation of highly purified, plant-derived cannabidiol (CBD), a form of cannabis that does not have the chemicals in it that produces the high associated with marijuana. It was approved for seizures associated with Lennox-Gastaut syndrome (LGS) or Draven syndrome.
Fintepla is currently under review by the European Medicines Agency and is in development in Japan. It is also being evaluated in a Phase III trial for treatment of seizures associated with Lennox-Gastaut syndrome.
