FDA Accepts Response to CRL for Etripamil (Cardamyst) for Treating PSVT

The US Food and Drug Administration (FDA) has accepted for review a response by Milestone Pharmaceuticals to issues raised in the Complete Response Letter (CRL) for etripamil (Cardamyst) nasal spray for paroxysmal supraventricular tachycardia (PSVT).1

Announced by Milestone on July 11, 2025, the FDA has also designated a new Prescription Drug User Fee Act (PDUFA) target action date of December 13, 2025. Milestone additionally described plans to extend its purchase and sale agreement (Royalty Purchase Agreement) with existing shareholder RTW Investments, LP, and some affiliates until December 31, 2025, with the funds from this extension supporting the planned launch of etripamil following FDA approval.1

“The FDA’s acceptance for review of our response to the CRL is a key milestone for CARDAMYST and we look forward to working with the Agency toward a potential approval decision later this year,” said Joe Oliveto, president and chief executive officer of Milestone Pharmaceuticals. “We are also pleased to amend our Royalty Purchase Agreement with RTW, underscoring their ongoing commitment to Milestone. The anticipated funds will position us well to execute on the commercial launch as we work to get CARDAMYST into the hands of patients with PSVT in need of a new treatment.”1

Etripamil, a novel calcium channel blocker nasal spray, is designed as a self-administered rapid response therapy for patients with PSVT and AFib-RVR. If approved, the spray will effectively bypass the need for immediate medical oversight, providing clinicians with new ways to enable patient self-management.1

Milestone’s original New Drug Application (NDA) submission was based on data from the RAPID trial, the second part of the NODE-301 study. It was a multicenter, randomized, placebo-controlled trial investigating the safety and efficacy of intranasal etripamil 70 mg for PSVT.2

Patients in RAPID were randomized in a 1:1 ratio to receive either etripamil or placebo. Upon experiencing symptoms of PSVT, participants would self-administer an initial 70 mg dose, with an optional second dose if symptoms persisted beyond 10 minutes. Results showed the etripamil cohort saw substantially higher greater Kaplan-Meier estimated conversion rates within 30 minutes. No safety or efficacy concerns were raised during the trial.1

Milestone Pharma submitted their initial NDA to the FDA on October 24, 2024. Before the close of 2024, the Company announced receipt of a Refusal to File Letter from the FDA, which stated the application was not sufficiently complete to permit substantive review and requested clarification about the time of data recorded for adverse events in phase 3 clinical trials. In March 2024, the company announced that, following a Type A meeting with the FDA, they had resubmitted their NDA for etripamil nasal spray in PSVT.2

A year later, on March 28, 2025, the FDA issued a CRL to the NDA, citing 2 key Chemistry, Manufacturing, and Controls issues without any concerns regarding clinical safety or efficacy data. The CRL requested that Milestone submit additional information on nitrosamine impurities, based on draft guidance issued after the initial NDA submission. The Agency also required a facility inspection that performs release testing for etripamil, to ensure compliance with Current Good Manufacturing Practices.3

Informed by the FDA meeting, Milestone submitted the response to the CRL on June 13, 2025, included the results of additional in-vitro studies conducted to meet updated FDA guidelines on nitrosamines. The Company also transferred the duties of the manufacturing testing facility named in the CRL to other contracted vendors that have had recent inspection history with the FDA.1

References

1. Milestone Pharmaceuticals Announces FDA Acceptance of the Company’s Response to the CRL for CARDAMYST (etripamil) Nasal Spray. Milestone Pharmaceuticals, Inc. July 11, 2025. Accessed July 11, 2025. https://investors.milestonepharma.com/news-releases/news-release-details/milestone-pharmaceuticals-announces-fda-acceptance-companys

2. Campbell P. FDA Issues CRL for Etripamil Nasal Spray (Cardamyst) in PSVT. HCPLive. March 28, 2025. Accessed July 11, 2025. https://www.hcplive.com/view/fda-issues-crl-for-etripamil-nasal-spray-cardamyst-in-psvt

3. FDA Issues Complete Response Letter for Etripamil for PSVT. Milestone Pharmaceuticals, Inc. March 28, 2025. Accessed July 11, 2025. https://investors.milestonepharma.com/news-releases/news-release-details/fda-issues-complete-response-letter-etripamil-psvt