FDA Rejects Milestone Pharmaceuticals' Tachycardia Drug, Sending Stock Plummeting

Milestone Pharmaceuticals faced a significant setback on Friday as the U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) rejecting the company's cardiovascular drug Cardamyst. The news sent Milestone's stock crashing by more than 60%, dealing a blow to the company's ambitions in the treatment of paroxysmal supraventricular tachycardia (PSVT).

Regulatory Hurdles for Cardamyst

Cardamyst, a novel calcium channel blocker formulated as a nasal spray, was developed to offer patients with PSVT a convenient alternative to hospital-based treatments. The drug's journey through the regulatory process has been fraught with challenges. In December 2023, the FDA issued a Refusal to File letter, citing insufficient information in the initial application. Milestone subsequently refiled in March 2024 with additional data, and the FDA accepted the application in May of that year.

The recent CRL focused on two key chemistry, manufacturing, and controls (CMC) issues:

1. The FDA requested additional information on nitrosamine impurities, based on new draft guidance issued after the submission of the New Drug Application (NDA).
2. The agency required the completion of an inspection at the facility responsible for release testing of Cardamyst, which had changed ownership during the review process.

Clinical Promise and Unmet Need

Despite the regulatory setback, Cardamyst has shown promising results in clinical trials. The pivotal Phase III RAPID trial demonstrated that the drug was "twice as effective and three times as fast as placebo" in normalizing heart rhythm, according to Milestone's NDA submission.

PSVT affects approximately 2 million people in the United States and is characterized by episodes of rapid heart rate, often exceeding 150 to 200 beats per minute. The condition can cause significant distress to patients due to its unpredictable nature.

Joe Oliveto, CEO of Milestone Pharmaceuticals, emphasized the high unmet need in PSVT treatment, stating, "You don't know when [events are] going to come and how bad it's going to be and how long it's going to last." Cardamyst was positioned to offer patients "a little bit of peace of mind" by allowing them to manage PSVT events without requiring hospitalization.

Market Implications and Future Outlook

The rejection of Cardamyst has significant implications for both Milestone Pharmaceuticals and the broader PSVT treatment landscape. Prior to the FDA's decision, Milestone had been actively preparing for the drug's launch, including hiring a sales management team.

Cardamyst would have been the first new drug approved for PSVT since adenosine, an intravenous medication used in emergency rooms, received FDA approval in 1989. The lack of alternative treatments in development for PSVT underscores the potential impact of Cardamyst's rejection on patients seeking new options.

In response to the CRL, Oliveto stated, "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." The company plans to request a Type A meeting with the FDA to address the issues raised in the rejection letter and determine the path forward for Cardamyst.