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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.

STOCKHOLM, Feb. 14, 2024 /PRNewswire/ -- Beactica Therapeutics AB, the Swedish precision oncology company, today announced that its TEAD programme has been selected for a late-breaking presentation at the American Association for Cancer Research's Annual Meeting 2024. The conference will take place on April 5-10, 2024 in San Diego, California. Dr Peter Brandt, Head of Chemistry, will present a poster entitled Degraders of TEAD transcription factors based on interface 3 binders on Sunday April 7, 2024, at 1:30 PM – 5:00 PM. The location is at the San Diego Convention Center, Section 52, abstract presentation number: LB029. The session title is Late-Breaking Research: Chemistry. The presentation will include new positive results from studies with novel proteolysis-targeting degraders of TEAD based on interface 3-binding ligands under development by Beactica. This will include head-to-head in vitro comparisons with other classes of TEAD modulators in clinical development such as palmitoylation inhibitors and direct YAP–TEAD protein–protein interaction inhibitors. The work to be presented contains contributions by Beactica's collaborators at the National Center for Advancing Translational Sciences (NCATS), one of 27 institutes and centers at the U.S. National Institutes of Health (NIH). Organised by the American Association for Cancer Research, the AACR Annual Meeting is the largest and most important cancer drug discovery event in the world. It has an anticipated attendance of more than 20 000 scientists, clinicians, advocates, and other attendees. The event spans integrative cancer science, global impact, individualised patient care and showcases the best and most up-to-date cancer science available. About TEAD TEAD 1–4 (Transcriptional Enhanced Associate Domain) are transcription factors that together with its coactivators YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif) play key roles in the Hippo signalling pathway that regulates cell proliferation, apoptosis, and stemness. Dysregulation of the Hippo pathway and subsequent activation of TEAD has been reported in a wide range of cancers such as squamous cell carcinoma, head and neck, gynaecological, and gastrointestinal cancers. The first clinical proof-of-concept for drugging the Hippo–YAP–TEAD pathway was achieved with the TEAD inhibitor VT3989 and was presented at the American Association for Cancer Research (AACR) Annual Meeting in April 2023. About Beactica Therapeutics Beactica Therapeutics AB is a privately held precision oncology company committed to the fight against cancer. The company is advancing a pipeline of novel small molecule therapeutics with a focus to treat genetically defined cancers with significant unmet medical need. Beactica's approach is centered around targeting synthetically lethal disease proteins with allosteric modulators and targeted protein degraders. Beactica deliver value to patients and shareholders by advancing its programmes to clinical proof of concept. For more information, please visit . Beactica Therapeutics Contact Per Källblad M.Sc. Ph.D. CEO [email protected] Tel: +46 18 56 08 80 The following files are available for download: SOURCE Beactica Therapeutics AB