Milestone Pharmaceuticals' plans to launch its novel treatment for paroxysmal supraventricular tachycardia (PSVT) have hit a significant roadblock as the U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) for the company's New Drug Application (NDA) for Cardamyst nasal spray.
The FDA's decision, which delays the potential approval of etripamil (Cardamyst) for converting acute episodes of PSVT to normal sinus rhythm in adults, was not based on concerns about the drug's safety or efficacy. Instead, the agency cited chemistry, manufacturing, and controls (CMC) issues that need to be addressed before approval can be granted.
Regulatory Challenges and Timing Issues
According to regulatory filings, the FDA specifically requested additional data on nitrosamine impurities based on new draft guidance published in September 2024. This guidance was issued months after Milestone had already resubmitted its NDA, creating an unexpected hurdle for the company.
The FDA also flagged the need for an inspection at a third-party facility that performs release testing for the product. This facility changed ownership during the NDA review period, necessitating a new inspection before approval.
Milestone Pharmaceuticals is actively working to address these concerns, with ongoing assays to meet the new impurity testing requirements. Results from these tests are expected in April, and the company anticipates scheduling a Type A meeting with the FDA in May or June to determine the path forward for resubmission.
Market Response and Financial Implications
Following the announcement, TD Cowen downgraded Milestone Pharmaceuticals from Buy to Hold and suspended its price target. Analysts cited the CRL as "upending imminent launch plans" with unclear timelines for NDA resubmission.
TD Securities expressed particular concern about the company's financial position in light of the extended regulatory timeline. As of Q4 2024, Milestone reported cash reserves of approximately $69.7 million, which analysts suggest may not be sufficient to support both the extended regulatory process and a potential commercial launch.
"Commercialization prospects are also constrained by limited capital," noted TD Cowen analysts in their downgrade report, highlighting the dual challenges of regulatory uncertainty and financial constraints.
Clinical Context and Market Opportunity
Etripamil represents a potentially significant advancement in the treatment of PSVT, a condition characterized by episodes of rapid heartbeat that start and stop suddenly. Current treatments often require medical intervention in emergency settings, while etripamil is designed as a self-administered nasal spray that patients could use at home during acute episodes.
PSVT affects approximately 500,000 people in the United States, with many patients experiencing recurrent episodes that significantly impact quality of life and result in frequent emergency department visits. A self-administered therapy could potentially reduce healthcare utilization and improve patient outcomes.
Path Forward
The regulatory setback creates significant uncertainty for Milestone Pharmaceuticals, which had been positioning etripamil as its lead product candidate. The company must now navigate both the technical requirements to address the FDA's concerns and the financial challenges of an extended timeline.
Industry observers note that while the issues raised in the CRL appear addressable, the timing of resubmission and potential approval remains unclear. This uncertainty is compounded by concerns about the FDA's operational efficiency, which TD analysts specifically mentioned in their downgrade rationale.
Milestone Pharmaceuticals has not yet provided detailed guidance on how long addressing the FDA's concerns might take or how this delay might impact their commercialization strategy and financial planning.
