FDA Rejects Milestone Pharmaceuticals’ Etripamil Nasal Spray for PSVT
The FDA declined to approve Milestone Pharmaceuticals' etripamil nasal spray (Cardamyst) for treating paroxysmal supraventricular tachycardia (PSVT)12.
The rejection was due to two chemistry, manufacturing, and controls (CMC) issues, not clinical safety or efficacy concerns13.
Milestone's stock price plummeted, falling as much as 66.7% to a record low of 75 cents following the news2.
The FDA requested additional information on nitrosamine impurities and an inspection of a facility that performs release testing for etripamil13.
Etripamil is designed to be a self-administered, rapid-response therapy for PSVT, potentially offering a more convenient alternative to emergency room visits3.
Milestone plans to request a Type A meeting with the FDA to discuss addressing the issues raised in the Complete Response Letter18.
As of December 31, 2024, Milestone Pharmaceuticals had $69.7 million in cash, cash equivalents, and short-term investments8.
Background
Etripamil is a calcium channel blocker nasal spray developed by Milestone Pharmaceuticals to treat paroxysmal supraventricular tachycardia (PSVT), a type of abnormal heart rhythm13. The drug, intended to be marketed as Cardamyst, was designed as a self-administered treatment that patients could use to manage their PSVT symptoms without immediate medical supervision35.
FDA Rejection and Reasons
On March 28, 2025, the U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) for etripamil, declining to approve the drug in its current form1. The FDA's decision was based on two key chemistry, manufacturing, and controls (CMC) issues:
Additional information on nitrosamine impurities was requested, based on new draft guidance issued after the New Drug Application (NDA) submission13.
An inspection is required at a facility that performs release testing for etripamil to ensure compliance with Current Good Manufacturing Practices. This facility changed ownership during the review of the NDA13.
Importantly, the FDA did not raise any concerns regarding the clinical safety or efficacy data of etripamil13.
Market Impact
The news of the FDA rejection had a significant impact on Milestone Pharmaceuticals' stock price. Shares of the company fell as much as 66.7% to a record low of 75 cents following the announcement2. By afternoon trading, the stock was down 59% at 92 cents2.
Company Response and Future Plans
Milestone Pharmaceuticals expressed disappointment with the CRL but remains committed to the potential of Cardamyst as a novel treatment option for PSVT patients18. The company plans to:
Evaluate the feedback provided by the FDA1.
Request a Type A meeting to discuss the issues raised in the CRL18.
Collaborate with the FDA to address the issues in a resubmission1.
Joe Oliveto, President and CEO of Milestone Pharmaceuticals, stated that the company is confident in its ability to work with the FDA to resolve the issues18.
Financial Position
As of December 31, 2024, Milestone Pharmaceuticals reported having $69.7 million in cash, cash equivalents, and short-term investments8. This financial position will be crucial as the company works to address the FDA's concerns and potentially resubmit its application for etripamil.
Sources:
1. https://www.morningstar.com/news/dow-jones/202503284145/fda-rejects-milestone-pharmaceuticals-etripamil-nasal-spray
2. https://www.tradingview.com/news/reuters.com,2025:newsml_L3N3QB1B7:0-milestone-pharma-hits-record-low-after-fda-declines-to-approve-heart-rhythm-nasal-spray/
3. https://www.fiercepharma.com/manufacturing/manufacturing-issues-trip-milestones-long-awaited-fda-milestone
5. https://cardiovascularbusiness.com/topics/clinical/heart-rhythm/fda-chooses-not-approve-new-nasal-spray-heart-rhythm-issues
8. https://www.globenewswire.com/news-release/2025/03/28/3051260/0/en/FDA-Issues-Complete-Response-Letter-for-Etripamil-for-PSVT.html