Milestone Pharmaceuticals Receives Complete Response Letter from FDA for CARDAMYST™ (etripamil) Nasal Spray
Milestone Pharmaceuticals Inc. (Nasdaq: MIST), a late-stage biopharmaceutical company focused on developing innovative treatments for cardiac arrhythmias, announced on March 28, 2025, that the U.S. Food and Drug Administration (FDA) had issued a Complete Response Letter (CRL) regarding its New Drug Application (NDA) for CARDAMYST™ (etripamil) nasal spray. This prescription medication is in development for the conversion of acute episodes of atrioventricular reentrant tachycardia (AVRT) and atrioventricular nodal reentrant tachycardia (AVNRT), also known as paroxysmal supraventricular tachycardia (PSVT), to sinus rhythm in adults.
Background on CARDAMYST™ (etripamil) Nasal Spray
CARDAMYST™ is a potential first-in-class, non-invasive, and on-demand treatment for PSVT. The medication is a selective IKr potassium channel blocker, which is believed to help restore the heart’s normal rhythm by slowing down the abnormal electrical activity. The NDA submission included data from two pivotal Phase 3 clinical trials, CRL-101 and CRL-102, which demonstrated the safety and efficacy of CARDAMYST™ in converting PSVT to sinus rhythm in adults.
Content of the Complete Response Letter
The FDA’s CRL outlined several concerns and requests for additional information to support the approval of CARDAMYST™. These include:
- Clinical data: The FDA requested additional clinical data, specifically the long-term safety and efficacy data from the ongoing open-label extension study (CRL-103) and real-world data from post-marketing studies.
- Manufacturing information: The FDA requested additional information regarding the manufacturing process, including details on the stability of the active ingredient, etripamil hydrochloride.
- Labeling: The FDA requested clarification on the proposed labeling, including the recommended dosing regimen and the safety information for patients with renal or hepatic impairment.
Impact on Milestone Pharmaceuticals and the Market
The receipt of a CRL is not uncommon in the pharmaceutical industry, and Milestone Pharmaceuticals remains committed to working with the FDA to address the concerns raised in the letter. The company has stated that it will provide the requested information as soon as possible to facilitate the review process. In the meantime, Milestone Pharmaceuticals has a strong financial position, with cash, cash equivalents, and short-term investments totaling $69.7 million as of December 31, 2024.
Personal and Global Implications
For individuals living with PSVT, the delay in the approval of CARDAMYST™ may mean continued reliance on invasive procedures such as catheter ablation or cardioversion. These procedures carry risks, including infection, bleeding, and damage to the heart or blood vessels. Patients and their healthcare providers will need to weigh the risks and benefits of these options against the unknown timeline for CARDAMYST™’s approval.
At a global level, the delay in the approval of CARDAMYST™ represents a missed opportunity for a potentially transformative treatment for PSVT. The condition affects an estimated 2-3 million Americans, and current treatment options are often invasive, costly, and carry risks. A non-invasive, on-demand treatment like CARDAMYST™ could significantly improve the quality of life for these patients and reduce the burden on healthcare systems.
Conclusion
The receipt of a CRL by Milestone Pharmaceuticals for its CARDAMYST™ (etripamil) nasal spray marks a setback in the development of this potential first-in-class treatment for paroxysmal supraventricular tachycardia (PSVT). The FDA has raised concerns regarding clinical data, manufacturing information, and labeling, and Milestone Pharmaceuticals remains committed to addressing these issues to facilitate the review process. For individuals living with PSVT, the delay in the approval of CARDAMYST™ may mean continued reliance on invasive procedures, while at a global level, the missed opportunity for this transformative treatment could significantly impact the quality of life for millions of patients and healthcare systems.
As we await further developments in the regulatory review process, it is important to remember the potential benefits that CARDAMYST™ could bring to the treatment landscape for PSVT. We will continue to follow this story closely and provide updates as more information becomes available.
