Elamipretide Hydrochloride

Advisory Committee Voted 10 to 6 in Favor, Concluding that Elamipretide is Effective for the Treatment of Barth Syndrome Elamipretide NDA Received Priority Review with a PDUFA Action Date of January 29, 2025 If Approved, Elamipretide Would Be the First Therapy for Barth Syndrome, a Life-Threatening Ultra-Rare Mitochondrial Disease NEEDHAM, Mass., Oct. 11, 2024 /PRNewswire/ -- Stealth BioTherapeutics Inc. (the "Company" or "Stealth"), a clinical-stage biotechnology company focused on the discovery, development and commercialization of novel therapies for diseases involving mitochondrial dysfunction, today announced that the U.S. Food and Drug Administration ("FDA") Cardiovascular and Renal Drugs Advisory Committee ("CRDAC") voted 10 to 6 in favor of Stealth's New Drug Application ("NDA"), concluding that elamipretide is effective for the treatment of patients with Barth syndrome. The CRDAC discussed the benefits and risks of elamipretide for the treatment of Barth syndrome, including results from the TAZPOWER Part 2 baseline-controlled extension study, the SPIBA-001 Phase 3 natural history control study, and additional supportive biomarker and preclinical data. The CRDAC's vote, while not binding, will be considered by the FDA when making its decision regarding the potential approval of elamipretide for Barth syndrome. If approved, elamipretide would be the first therapy for this ultra-rare, progressive, life-shortening, cardioskeletal disease that affects approximately 150 individuals in the United States. The NDA for elamipretide was granted priority review and has been assigned a Prescription Drug User Fee Act ("PDUFA") action date of January 29, 2025. "We are pleased that the FDA advisory committee has thoughtfully considered the elamipretide data package – including the positive results from the rigorously constructed natural history control trial, the durable open-label extension data, and expanded access cases – and recognized that these data support the potential of elamipretide to improve the lives of patients with this devastating disease," said Reenie McCarthy, Chief Executive Officer. "We are grateful to the many patients, caregivers, advocates, and healthcare providers who shared their perspectives and experiences with the advisory committee. We look forward to collaborative conversations with the FDA as the agency completes its review of elamipretide, the first potential therapy for Barth syndrome." If approved, this would be the first marketing authorization for elamipretide, a first-in-class mitochondria-targeted therapeutic. In addition to Barth syndrome, elamipretide is in Phase 3 trials for primary mitochondrial myopathy, with pivotal data expected by the end of 2024, and for dry age-related macular degeneration. About Barth Syndrome Barth syndrome is an ultra-rare genetic condition characterized by cardiac abnormalities leading to exercise intolerance, muscle weakness, debilitating fatigue, heart failure, recurrent infections, and delayed growth. The disease is associated with reduced life expectancy, with 85% of early deaths occurring by age 5. Barth syndrome occurs primarily in males and is estimated to affect one in 1,000,000 males worldwide or around 150 individuals in the United States. There are currently no FDA- or EMA-approved therapies for patients with Barth syndrome. Elamipretide has Orphan Drug, Fast Track and Rare Pediatric Designation from the FDA and Orphan Drug Designation from the EMA for the treatment of Barth syndrome. About Stealth BioTherapeutics Our mission is to develop novel therapies to improve the lives of patients living with diseases of mitochondrial dysfunction. Our lead product candidate, elamipretide, is under review for Barth syndrome and in late-stage development for primary mitochondrial myopathy and dry age-related macular degeneration. We are also evaluating a topical ophthalmic formulation of our second-generation clinical-stage candidate, bevemipretide (SBT-272), for dry age-related macular degeneration, and have a deep pipeline of novel compounds under evaluation for rare neurological and cardiac disease indications. Media Contact Anna Stallmann Communications Anna Stallmann [email protected] Investor Contact Precision AQ Austin Murtagh [email protected] SOURCE Stealth BioTherapeutics Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

As well as the committee, the adcomm heard from patients, doctors, and parents of children with Barth syndrome. Credit: Salivanchuk Semen via Shutterstock. A US Food and Drug Administration (FDA) advisory committee (AdCom) has voted in support of Stealth BioTherapeutics ’ first-line Barth syndrome drug, despite a trial studying the drug not meeting its primary endpoint. The Cardiovascular and Renal Drugs Advisory Committee voted 10-6 supporting Stealth’s elamipretide for the treatment of Barth syndrome, an ultra-rare genetic disorder caused by mutations in the TAZ gene, which primarily affects males. The life-threatening disease – which causes symptoms like cardiomyopathy and growth delays – has no cure, and no other therapies in late-stage clinical development, according to the Barth syndrome Foundation. The FDA is expected to decide whether to approve the new drug application in January 2025. During the committee meeting, the panel discussed findings from the SPIBA-201 clinical trial (NCT03098797). The trial, which assessed the impact of elamipretide in 12 male patients over 12 weeks of daily treatment, failed to meet the primary endpoint of improving walking distance. Patients treated with elamipretide walked an average of 443.1 metres compared to 443.9 for patients on placebo. While there was a slight increase in walking distance from baseline – 43 metres for the elamipretide group compared to 31 metres for placebo – the difference was not statistically significant. The FDA reviewers told the committee that Stealth’s drug did not meet statistical significance in the primary or secondary endpoints. See Also: Activist investor Starboard cries foul play in exec U-turn at Pfizer Activist investor Starboard forges $1bn stake in Pfizer to swing profits However, the AdCom heard from patients, doctors, and parents of children with Barth syndrome, saying that the drug had helped patients gain weight, strength, and stamina, advocating for elamipretide’s approval. Jacob Wilson, a 24-year-old male with Barth syndrome told the panel the medicine “made him feel like a new person”. Elamipretide has previously faced rejection from the FDA. In August 2021, Stealth filed a new drug application (NDA) for the candidate, however the FDA responded in October of the same year with a refuse-to-file letter, stating that the NDA “did not contain an adequate and well-controlled trial that provides evidence of effectiveness”. Stealth did not conduct another Phase III study, despite advice from the FDA to do so.  Its initial application was linked to the SPIBA-001 study (NCT04689360), a Phase III trial that included both treated patients from SPIBA-201 and new, untreated patients. Despite the trial meeting its primary endpoint, the FDA raised concerns about how the data were analysed. Results were compared to an open-label extension from the Phase II/III SPIBA-201 crossover study and historical control data from 19 subjects monitored between 2012 and 2019 at the Johns Hopkins Kennedy-Krieger Institute. This approach was criticised by the FDA. The panel raised concerns about two potential biases in the SPIBA-001 trial design. Selection bias could result from differences in the natural history control subsample, while a confounding bias may arise due to the lack of randomisation. The panel also argued that the propensity score method used in the Phase III trial failed to adequately correct for these biases. Despite this, the committee ultimately decided to vote in favour of the mitochondrial-targeting peptide drug. The committee also acknowledged “the devastating impact of Barth’s” and “the significant unmet medical need” in a document released in advance of the AdCom meeting. This unmet need was reiterated by Emily Milligan, executive director of the Barth syndrome Foundation: “We strongly urge the FDA to move swiftly toward approving elamipretide for use in Barth syndrome, bringing patients closer to having sustained access to this critical therapy. Our plight is not just about Barth syndrome—it sets an important precedent for how we address the unmet needs of patients and families affected by many rare diseases.” Attention will now turn to the 29 January decision date, as in the briefing document before the AdCom, the FDA said it does not believe that the available evidence establishes the effectiveness of elamipretide for Barth syndrome. While the FDA takes AdCom recommendations into consideration, it are not required to follow them.