FDA Rejects Milestone Pharmaceuticals' Nasal Spray for PSVT, Citing Manufacturing Issues

Milestone Pharmaceuticals' long-awaited journey to FDA approval for its novel nasal spray treatment, Cardamyst (etripamil), has hit a significant roadblock. The U.S. Food and Drug Administration (FDA) has issued a complete response letter (CRL) rejecting the company's application for the treatment of paroxysmal supraventricular tachycardia (PSVT), a type of abnormal heart rhythm.

Manufacturing Concerns Prompt FDA Rejection

The FDA's decision hinges on two key chemistry, manufacturing, and control (CMC) issues:

1. Nitrosamine impurities: Milestone must address a problem related to these potentially harmful compounds.
2. Facility inspection: An FDA inspection is required at a facility responsible for "release testing" of the drug.

Notably, the manufacturing facility in question changed ownership during the FDA's review process, further complicating the situation.

Joe Oliveto, Milestone's CEO, expressed disappointment but remained committed to Cardamyst's potential, stating, "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. Our team is evaluating the feedback provided and intends to request a Type A meeting to discuss the issues raised in the CRL."

Clinical Efficacy and Future Prospects

Despite the setback, the FDA did not raise concerns about Cardamyst's clinical safety or efficacy. The nasal spray has shown promising results in clinical trials:

• In a phase 3 trial, Cardamyst was twice as effective and worked three times as fast as a placebo in restoring normal heart rhythm.
• 64% of patients on etripamil achieved termination of their PSVT compared to 31% of those on placebo.

If approved, Cardamyst would become the first self-administered treatment for managing PSVT symptoms, offering a more convenient alternative to emergency room visits for intravenous treatment.

Broader Implications and Next Steps

Milestone Pharmaceuticals, now in its 22nd year, faces another delay in bringing its first product to market. The company reported $70 million in cash and cash equivalents at the start of the year, providing some financial cushion as it addresses the FDA's concerns.

Looking ahead, Milestone aims to expand Cardamyst's potential applications beyond the estimated 2 million PSVT patients in the U.S. The company is also pursuing approval for atrial fibrillation with rapid ventricular response (AFib-RVR), which affects approximately 10-12 million U.S. patients.

As Milestone works to address the manufacturing issues, the pharmaceutical industry will be watching closely to see how quickly the company can resubmit its application and potentially bring this innovative treatment to market.