Sarepta Therapeutics, Inc.

Dive Brief:The Food and Drug Administration needs stricter standards for the accelerated approval process to ensure patients and the healthcare system dont waste money on ineffective treatments, according to a report issued Tuesday from a federal watchdogSpurred by controversy over the 2021 approval of Biogens Alzheimers disease drug Aduhelm, the office of the inspector general for the Health and Human Services department examined 24 FDA reviews that led to accelerated approvals of new medicines. The office identified concerns with three, including Aduhelm.In those cases, the FDA failed to follow its own best practices in data analysis, held meetings with sponsors that werent properly documented and suffered from a lack of oversight that could have been triggered by conflicts within the agency, the report said. These three cases underscore the need for additional guardrails, the report said.Dive Insight:The inspector generals office has two main recommendations to improve the accelerated approvals process. The FDA agreed with the watchdog that meetings with sponsors need to be better documented and said its already taken steps to improve its procedures. But the agency disagreed with the watchdogs second recommendation, to outline certain factors that would trigger greater oversight.Specifically, the inspector generals office suggested the agencys accelerated approvals council itself a new creation should be required to meet when FDA reviewers dont reach consensus on an application, an advisory committee raises significant concerns or when a drugmaker relies on analyses not included in the original plan to win approval of a medicine. Other factors could be set up to trigger a meeting as well, it said.The accelerated approval pathway exists to allow drugs to reach the market faster based on promising signs in research, such as a reduction in a biomarker linked to disease. Drugmakers are then required to keep testing the medicines to show a clinical benefit. The pathway is often used for diseases that dont have adequate treatments and have patient advocates pushing the FDA to approve new medicines.In the case of Aduhelm, messy study results led to unorthodox practices at the FDA that have already been well documented. Biogen ended up pulling the drug off the market in 2024. The inspector generals office also found problems with the reviews of Makena, a drug to reduce the risk of preterm birth, and Exondys 51 to treat Duchenne muscular dystrophy.The HHS inspector generals office detailed some of the behind-the-scenes action on the applications. In the case of Exondys, the director of the FDAs drug division overruled the review team, which had decided the research didnt support approval. A dispute between high-ranking officials followed, and the FDA commissioner ultimately decided to approve the medicine.The inspector generals office chose 10 of the drugs for review after they were flagged by stakeholders as potentially problematic. It chose the other 14 at random. The office noted that both Aduhelm and Makena are no longer for sale. Exondys, sold by Sarepta Therapeutics, remains on the market, but its required trial to demonstrate clinical benefit has been delayed. '

The upheaval over the FDA’s accelerated approval of Biogen’s now-pulled Alzheimer’s drug Aduhelm in 2021 led HHS’ Office of Inspector General to review 24 other accelerated approvals to see if there were similar deficiencies. Sarepta’s muscular dystrophy drug Exondys 51 and Covis’ recently pulled preterm birth drug Makena both fit the description of nonstandard FDA practices. OIG outlines in a new report how for these three accelerated approvals, the FDA “deviated” from the 21 others “in ways that raised concerns.” OIG said the three cases “underscore the need for additional guardrails in certain circumstances” for the agency. For both Aduhelm and Exondys 51, OIG found that the FDA shifted away from its standard practice by evaluating data analyses “that were not included in the sponsors’ original analysis plans (i.e., changing the measure used to determine effectiveness and/or changing the approach to analyzing the data).” In the case of Makena, which failed a confirmatory trial and was pulled after a long fight , FDA reviewers ultimately supported accelerated approval, “but only after multiple review rounds and sponsor commitments to resolve concerns through confirmatory trials after approval.” OIG noted other inconsistencies, including that the administrative file for Aduhelm at the FDA appears incorrect, as it notes only 13 meetings between the FDA and Biogen, while a 2022 congressional investigation said the agency and Biogen convened at least 40 meetings. In the case of Exondys 51, approved in 2016 and yet to complete its confirmatory trial, the report notes that the FDA “also veered from best practices by redirecting the sponsor from the sponsor’s original analysis plan” and towards accelerated approval. OIG notes that the dispute over Sarepta’s drug also referred to “atypical and excessive involvement” by former CDER director Janet Woodcock “by means such as: (1) taking a large role in the early stages of the FDA review of the drug, (2) planning and speaking at the advisory committee meeting, and (3) making clear an intention to approve the drug regardless of the review team’s conclusions.” And while Sarepta has dragged its feet on Exondys 51’s confirmatory trial, OIG points out that the agency has since used the approval as the basis for granting accelerated approval to three other Duchenne muscular dystrophy drugs.

WATERTOWN, Mass.--( BUSINESS WIRE )-- Dyno Therapeutics, Inc. , a genetic technologies company applying artificial intelligence (AI) to enable in vivo gene delivery, today announced that Roche (SIX: RO, ROG; OTCQX: RHHBY) has exercised its option to license a novel capsid for use in a gene therapy program for an undisclosed neurological disease indication. The capsid license is pursuant to the agreement between Dyno and Roche originally announced in May 2020. Dyno’s platform applies AI and high-throughput in vivo data to solve the most critical challenge facing gene therapy developers: gene delivery. While naturally occurring AAV capsids lack precise targeting to deliver medicine to the right cells, are difficult to manufacture, and have pre-existing immunity, Dyno’s platform navigates the deep sequence space to create synthetic AAV capsids with optimized properties that outperform existing capsids. Dyno’s industry-leading gene delivery solutions thereby enable its partners to develop next-generation gene therapies that can potentially benefit all patients. “ Granting the license of a Dyno capsid to a leading drug development company like Roche is a significant achievement for AI in gene therapy,” said Eric Kelsic, Ph.D., Founder and Chief Executive Officer of Dyno. “ This latest advancement in one of our partnerships is further validation of the proven effectiveness of our gene delivery platform and continued and rapid advancement of our sequence design capabilities.” Roche’s option exercise triggers a US$7 million payment to Dyno, with the potential to earn over US$220 million in associated development, regulatory, and commercial milestone payments plus royalties in connection with Roche’s use of Dyno’s capsid to develop and commercialize a neurological disease-targeting gene therapy. The exercise of this license option concludes Dyno and Roche’s initial collaboration. In October 2024, the companies announced a second collaboration agreement providing Roche with further access to Dyno’s field-leading platform and sequence design methods for the treatment of neurological diseases, including Dyno’s Low-shot Efficient Accelerated Performance (LEAP SM ) technology , which accelerates gene therapy vector engineering by generating high-performance out-of-distribution capsid proteins. About Dyno Therapeutics Dyno Therapeutics is building high-performance genetic technologies that transform patient health by overcoming the in vivo gene delivery challenge for therapeutic developers. Dyno’s platform integrates AI with high-throughput experimentation to accelerate the design of AAV capsids that significantly outperform existing gene delivery vectors. Just as exponential breakthroughs in computer chip technology powered the AI revolution, Dyno’s versatile platform is leveraging foundational advances in in vivo multiplexing technologies and high-performance computing to address a broad range of therapeutic challenges. Dyno has empowered therapeutic innovation through partnerships with leading gene therapy developers, including Astellas, Roche, and Sarepta, and with technology companies including NVIDIA. Visit www.dynotx.com for additional information.