Milestone's shares plummet as FDA rejects heart drug again

Milestone Pharmaceuticals recently faced another setback as its nasal spray, etripamil, failed to gain approval from the US Food and Drug Administration (FDA) for the treatment of paroxysmal supraventricular tachycardia (PSVT), a type of arrhythmia disorder. The FDA's rejection was communicated through a complete response letter, highlighting two main issues related to Chemistry, Manufacturing, and Controls (CMC).

The FDA pointed out the need for additional information concerning "nitrosamine impurities." These concerns emerged following the agency's release of new draft guidance after Milestone had already submitted its New Drug Application (NDA) for etripamil. Additionally, the FDA noted that the facility responsible for the release testing of etripamil needed an inspection due to a change in ownership during the review process. Importantly, no issues were raised regarding the drug's efficacy or safety. Despite this, the company's shares, traded under the ticker $MIST, took a significant hit, plummeting around 60% on the day of the announcement.

Milestone's journey with etripamil and the FDA has been fraught with challenges. A previous attempt to secure approval in 2023 was met with a refuse-to-file letter from the FDA, which requested further details on the "time of data recorded for adverse events" in the company’s pivotal studies. In an earlier hurdle, etripamil had not succeeded in a Phase 3 trial for PSVT back in 2020.

The most recent NDA submission was supported by data from two Phase 3 trials named RAPID and NODE-301. In the RAPID study, approximately 65% of patients receiving etripamil achieved sinus rhythm, or a normal heartbeat, within 30 minutes of treatment, compared to 31.2% of patients who received a placebo. These results, according to Milestone, were statistically significant.

Etripamil is designed as a calcium channel blocker that can be self-administered through a nasal spray, offering a potentially swift treatment option for PSVT patients who experience sudden rapid heartbeats that often necessitate emergency medical intervention. The aim of the drug is to provide swift relief and reduce the need for emergency room visits.

Prior to the FDA’s latest decision, Milestone had been gearing up for a "staged launch" of etripamil for PSVT, projected for the middle of the year. According to analysts from TD Cowen, the plan involved targeting an initial group of 10,000 to 12,000 physicians, primarily cardiologists. PSVT is estimated to affect less than 1% of the US population.

Beyond PSVT, Milestone sees potential for etripamil in treating atrial fibrillation, which represents a larger market opportunity. According to CEO Joseph Oliveto, the drug is currently undergoing Phase 2 trials for this condition. Oliveto discussed these prospects at the TD Cowen Health Care Conference in Boston earlier this year.

In a parallel development, etripamil had successfully passed a Phase 3 trial for PSVT patients in China as of September last year. This achievement, conducted in partnership with Milestone's Chinese collaborator, Ji Xing, has paved the way for a potential filing in China.

Despite the setbacks in the US, Milestone remains hopeful about the future potential of etripamil, both for PSVT and for broader applications in arrhythmia disorders. The company continues to engage with the FDA to address the concerns raised and remains committed to bringing this innovative treatment to patients in need.