Etripamil

Established in Montreal 22 years ago, Milestone Pharmaceuticals has gained its first FDA approval, winning a nod for Cardamyst, a nasal spray to treat sudden episodes of the heart racing condition paroxysmal supraventricular tachycardia (PSVT). Clearing clinical and regulatory hurdles in the development of a fast-acting nasal spray for a heart condition has given Milestone Pharmaceuticals its first FDA approval in its 22-year history.The U.S. regulator has signed off on Cardamyst (etripamil) to quell symptomatic episodes from paroxysmal supraventricular tachycardia (PSVT), which is a type of abnormal heart rhythm. Cardamyst becomes the first self-administered treatment patients can use to manage their PSVT symptoms.The calcium channel blocker is a convenient alternative to an emergency room visit, where patients receive an intravenous dose of a drug that “basically reboots your heart,” Milestone CEO Joe Oliveto said in an interview.“It’s only a few seconds but nevertheless, these people really don’t like it,” Oliveto said, adding that patients have told him receiving the IV treatment is “like a near death experience.”Nearly as traumatizing for PSVT patients are the heart racing episodes which come sporadically and without warning. Oliveto said some patients have described even just a 10-minute attack of palpitations as feeling like they had run a marathon.PSVT occurs when a short circuit rhythm develops in the upper chamber of the heart. It causes rapid heartbeat that starts and stops abruptly. The heart rate can run up to 230 beats per minute.The only treatments used to counter PSVT are prophylactics such as beta blockers, anti-arrhythmic drugs and other calcium channel blockers that are taken orally and provide mixed results in curbing the episodes.With its ability to provide potentially speedy relief, Oliveto believes  Cardamyst can give patients peace of mind and more flexibility as they plan their activities. Oliveto calls it “insurance in my pocket.”“Seventy percent of patients report anxiety even when they’re not in an event and that’s because they don’t know when an event is going to come,” Oliveto said. “Is it going to happen when I’m with my grand-kids or I’m at work at an important presentation or I’m on a plane to Europe. It’s like they’re walking on eggshells. It’s always there on their minds and the current solution is not great—a trip to the emergency department.” Results from a phase trial show that Cardamyst was twice as effective and worked three times as fast as a placebo in restoring normal heart rhythm. Of the patients on etripamil, 64% achieved termination of their PSVT compared to 31% of those on placebo.Getting that result took some time, however, after a phase 3 trial in 2020 came up short as Cardamyst failed to top placebo. After discussions with the FDA, Milestone got better test results when it allowed patients to use a second dose and adjusted to a shorter time frame (30 minutes) for measuring the success of the treatment.“The patient takes the dose, which is basically one spray in each nostril,” Oliveto said. “And if after 10 minutes, there’s no response, you take another one and that really boosted the efficacy for us to the data we have now. That gave us an extra 10 to 15% of patients who responded in that first half hour.”Milestone, which was established in Montreal, opened the fourth quarter with cash equivalents of $83 million. In a deal with RTW Investments, the company will receive $75 million in exchange for tiered royalties.The company will charge $1,649 per prescription of Cardamyst, "which aligns with net revenues to Milestone of between $500 and $1,000 per prescription,"  Lorenz Muller, chief commercial officer, said in a Monday webcast. While there are roughly 2 million people in the U.S. with PSVT, Milestone is hoping to gain approval for Cardamyst in a larger indication—atrial fibrillation with rapid ventricular response (AFib-RVR), which includes around 10 million to 12 million U.S. patients. With one nod in hand for Cardamyst, Oliveto believes a label expansion could be accomplished with one successful phase 3 trial.“PSVT opens everything up for us to be transformative. It transforms us from a development company into a commercial company,” Oliveto said. “It transforms us from a single indication to now starting the AFIB phase 3 indication.”Milestone was up more than 35% premarket Monday morning on the news. 

On what turned out to be a busy Monday at the FDA, the US regulator awarded a national priority voucher to a multiple myeloma treatment regimen from Johnson & Johnson following impressive Phase III results, while also loosening longstanding restrictions on real-world evidence (RWE) for medical device applications — and hinting it may do the same for drugs and biologics.Tecvayli-Darzalex voucherIn a nod to its clinical potential in multiple myeloma, Johnson & Johnson's combination of anti-BCMA bispecific Tecvayli (teclistamab-cqyv) plus Darzalex Faspro (daratumumab/hyaluronidase-fihj) became the latest recipient of a national priority voucher from the FDA, after the agency took notice of the Phase III MajesTEC-3 study results and liked what it saw."Within hours of the trial results being published in the American Society of Hematology (ASH) conference programme, FDA leaders read the study, consulted with internal experts, and the following day contacted the company to discuss a national priority voucher," FDA Commissioner Marty Makary said.Results from the trial, presented at ASH last week, showed that the Tecvayli-Darzalex Faspro combo achieved a three-year progression-free survival (PFS) rate of over 83%, compared to around 30% for the comparator arm (see – Spotlight On: J&J's eye-popping MajesTEC-3 data a win for Tecvayli, MM bispecifics).The latest voucher brings the total number of products receiving an award under the Commissioner's National Priority Voucher (CNPV) pilot programme to 16. The programme is designed to speed up reviews for products that are deemed "aligned with US national priorities." Review decisions are targeted for completion within one to two months after an application is submitted. The first product to win approval under the programme — the US-manufactured version of the antibiotic Augmentin XR (amoxicillin-clavulanate potassium) — was announced last week.RWE policy shiftMeanwhile, the FDA is also overhauling its approach to RWE, removing a major barrier that has historically limited its use in regulatory submissions. Previously, RWE required identifiable individual patient data, but the agency said Monday that de-identified datasets can now provide meaningful insights.For medical devices, the FDA will accept RWE without requiring that identifiable individual patient data collected from real-world data sources always be submitted in a marketing submission; it will "consider" updating its drug and biologic guidance to match..The agency said it is "responding to the position of many sponsors and data scientists that meaningful information can be extracted from some big data sources without private, individual information."While RWE has been more widely applied in medical device approvals, the restriction has limited the use of RWE in drug applications. Since 2016, the agency said just 35 drugs, biologics or vaccines have incorporated RWE into their submissions. The FDA will now evaluate RWE submissions on a case-by-case basis.The policy change unlocks access to massive de-identified databases that were previously unusable for regulatory submissions, including national cancer registries like the National Cancer Institute's Surveillance, Epidemiology, and End Results; hospital system databases; insurance claims data; and electronic health record networks, containing millions of patient records.New Enhertu, PCSK9 nodsBeyond policy shifts and priority vouchers, the FDA also handed down a pair of traditional approval Monday. The most notable went to AstraZeneca and Daiichi Sankyo's Enhertu (fam-trastuzumab deruxtecan-nxki). The HER2-targeting antibody-drug conjugate can now be used in combination with Roche’s Perjeta (pertuzumab) to treat adults with treatment-naïve, unresectable or metastatic HER2-positive breast cancer. For more details on the approval, see FDA greenlights Enhertu's move into first-line breast cancer.Meanwhile, third-generation PCSK9 inhibitor Lerochol (lerodalcibep-liga), developed by LIB Therapeutics, was cleared to help reduce LDL cholesterol (LDL-C) in adults with hypercholesterolaemia, including heterozygous familial hypercholesterolaemia.The filing was backed by data from the Phase III LIBerate programme, which enrolled over 2900 patients across diverse populations, including those with cardiovascular disease as well as those with heterozygous or homozygous familial hypercholesterolaemia.In clinical testing, Lerochol achieved sustained LDL-C reductions of 60% or more in patients with or at high risk of cardiovascular disease, and 50% or more in those with HeFH who have more severe LDL-C elevations. The drug was generally well tolerated with no treatment-related serious adverse events reported in long-term extension studies.Lerochol is expected to reach US pharmacies in spring 2026, initially as a pre-filled syringe, with an autoinjector device following later in the year. The company has submitted applications for approval in Europe as well, with a decision anticipated by mid-2026.Friday Cardamyst approvalLate on Friday, the FDA also approved a nasal spray that patients can self-administer at the first signs of paroxysmal supraventricular tachycardia (PSVT).Milestone Pharmaceuticals said the FDA's green light of the rapid-acting calcium channel blocker Cardamyst (etripamil), the company's first product, represents a breakthrough for patients who have endured the anxiety of never knowing when their heart rate might suddenly spike to 150-200 beats per minute, causing severe palpitations, shortness of breath and debilitating distress that could last for several hours.In the Phase III RAPID trial published in The Lancet, patients using Cardamyst were twice as likely to convert from supraventricular tachycardia to sinus rhythm within 30 minutes compared to placebo (64% versus 31%), and did so more than three times faster, with a median conversion time of 17 minutes versus 54 minutes. The approval draws on clinical data from over 1800 participants and 2000 PSVT episodes.Side effects were limited to mild, transient nasal discomfort, nasal congestion, rhinorrhoea, throat irritation, and epistaxis. Fewer than 2% of participants discontinued due to adverse events.CEO Joseph Oliveto said the company's "at-the-ready treatment option…addresses the unpredictable impact of PSVT by offering patients the freedom to manage episodes anytime and anywhere."