Established in Montreal 22 years ago, Milestone Pharmaceuticals still has work to do to gain its first FDA approval as the regulator has sent a complete response letter, citing two manufacturing issues for Cardamyst, a nasal spray to treat sudden episodes of the heart racing condition paroxysmal supraventricular tachycardia (PSVT).
Clearing clinical and regulatory hurdles in the development of a fast-acting nasal spray for a heart condition has been a challenge for Milestone Pharmaceutical in its 22 years.Now the wait will be longer for its first FDA approval as the regulator has rejected its application for Cardamyst (etripamil) to quell symptomatic episodes from paroxysmal supraventricular tachycardia (PSVT), which is a type of abnormal heart rhythm.In a complete response letter (CRL), the FDA cited two chemistry, manufacturing and control (CMC) issues. Milestone will have to address a problem with nitrosamine impurities. An FDA inspection also will be required at a facility that performs “release testing” for the drug, the company said in a release. During the FDA’s review of Milestone’s application, the manufacturing facility “changed ownership,” the company said.“We are deeply disappointed by the CRL but remain committed to the potential of Cardamyst as a novel treatment option that can help patients with PSVT. Our team is evaluating the feedback provided and intends to request a Type A meeting to discuss the issues raised in the CRL,” Joe Oliveto, Milestone’s CEO for the last eight years, said in a statement. “We are appreciative of the FDA’s efforts and are confident we can collaborate with the agency with the goal of addressing these issues in a resubmission.”Milestone said that the FDA did not raise any concerns with Cardamyst’s clinical safety or efficacy. The company opened the year with cash and cash equivalents of $70 million.With an approval, Cardamyst would become the first self-administered treatment patients can use to manage their PSVT symptoms. The calcium channel blocker is designed to be a more convenient alternative to an emergency room visit, where patients receive an intravenous dose of a drug that “basically reboots your heart,” Oliveto said in an interview two weeks ago.Results from a phase trial have shown that Cardamyst was twice as effective and worked three times as fast as a placebo in restoring normal heart rhythm. Of the patients on etripamil, 64% achieved termination of their PSVT compared to 31% of those on placebo.Getting that result took some time, however, after a phase 3 trial in 2020 came up short as Cardamyst failed to top placebo. After discussions with the FDA, Milestone got improved results when it allowed patients to use a second dose and adjusted to a shorter timeframe (30 minutes) for measuring the success of the treatment.There are roughly 2 million in the U.S. with PSVT. Beyond that, Milestone is hoping to gain approval for Cardamyst in a larger indication—atrial fibrillation with rapid ventricular response (AFib-RVR), which includes approximately 10–12 million U.S. patients.
