Mucopolysaccharidosis IV

Pictured: Rare disease ribbon with cut-outs of people/iStock, nambitomo The Bespoke Gene Therapy Consortium, a public-private collaboration involving the National Institutes of Health, FDA, industry and patient groups intended to help accelerate the delivery of AAV-based gene therapies for rare diseases, is making slow but steady progress, a representative said at the 2024 American Society of Gene & Cell Therapy (ASGCT) annual meeting. Launched in October 2021, the Bespoke Gene Therapy Consortium (BGTC) has more than $100 million in financial and in-kind commitments funded by a public-private entity called the Accelerating Medicines Partnership (AMP), through which the Foundation for the NIH (FNIH) administers funds provided by industry, government and nonprofits. Courtney Silverthorn, vice president of strategic alliances and innovation at FNIH’s AMP, told a Wednesday session that BGTC’s announcement last May at ASGCT 2023 identifying eight rare diseases for its clinical trial portfolio “really kicked things off” for the consortium. “The first year-and-a-half was designed to narrow down and finalize the clinical portfolio that would serve as the proof-of-concept for the goals and aims of the consortium,” Silverthorn said. Based on the early success of BGTC, FNIH is currently developing a similar cell therapy consortium that will be launched in 2025, according to Silverthorn. BGTC’s clinical trial portfolio includes eight diseases: Charcot-Marie-Tooth disease type 4J, congenital hereditary endothelial dystrophy, Morquio syndrome, multiple sulfatase deficiency, NPHP5 retinal degeneration, propionic acidemia, retinitis pigmentosa 45 and spastic paraplegia 50. Silverthorn said all readiness assessments have been completed for the eight assets in the clinical trial portfolio, while progress has also been made on manufacturing agreements. “All of the product for the BGTC is being donated partially or completely in kind to [FINH] as part of the consortium,” she added. BGCT’s private sector partners include 13 life sciences companies such as Biogen, Johnson & Johnson’s Janssen, Novartis, Pfizer, Regenxbio, Spark Therapeutics and Takeda. Last year, REGENEXBIO announced that its preclinical research in Morquio syndrome was selected for inclusion in the consortium’s clinical trial portfolio and that it was donating licenses for its NAV AAV8 and NAV AAV9 assets to the endeavor as a potential treatment for the rare inherited birth defect. In February 2024, BGTC published a “playbook” that lays out the critical steps before the submission of Investigational New Drug (IND) applications for the first human studies and includes regulatory best practices, as well as case studies of existing AAV gene therapies. “This is still a document in progress and we expect to have several more versions published over the next couple of years that will incorporate more of the learnings of the BGTC as we go through our clinical portfolio process,” Silverthorn said. Peter Marks, director of the FDA's Center for Biologics Evaluation and Research, in a recorded message at ASGCT 2024, made the case for the importance of BGTC and addressing the challenges faced by gene therapy developers. “This concept of a playbook to try to harmonize manufacturing protocols could really help us,” Marks said. “Automation could really bring us both a reduction in costs and an improvement in quality and consistency of products.” In a previous session at ASGCT, Marks hinted at future guidance from the FDA on other aspects of gene therapy development—namely, accelerated access. “I can’t get into the details,” he said. “But it may be helpful to the community to understand our thinking about how we look at accelerated approval in the gene therapy space.” Greg Slabodkin is the news editor at BioSpace. You can reach him at greg.slabodkin@biospace.com. Follow him on LinkedIn.

Pictured: A green, blue and pink ribbon representing rare disease advocacy/iStock, itakdalee Yesterday was Rare Disease Day 2024. It was a reminder of the importance of raising awareness for rare diseases—defined as those that affect fewer than 200,000 people in the U.S., but collectively affecting some 30 million Americans. While much has been achieved in improving access to lifesaving and life-changing treatments, much more remains to be done for patients with these disorders. Despite recent investment and breakthroughs for rare diseases, experts told BioSpace that helping a much larger patient population will require cross-sector support and desperately needed funding. We looked at some of the investments to date, as well as the biopharma industry’s promising pipelines and what is required to bring more groundbreaking therapies to patients with unmet medical needs. Not surprisingly, patient advocacy groups (PAGs) have been critical to the development of the first marketed drugs for certain rare diseases, including progeria and Friedreich’s ataxia. BioSpace spoke with leaders of PAGs formed by families coping with rare diseases, providing case studies on their partnerships with biopharma companies and the sharing of resources and expertise to maximize the impact of R&D and clinical trials. BioMarin Pharmaceutical picked the wrong week to disclose that it has been hit with a Department of Justice subpoena in connection with its sponsored testing programs for the rare disease therapies Vivizim—an FDA-approved enzyme replacement therapy for the treatment of Morquio A syndrome—and Naglazyme, an enzyme replacement therapy approved for mucopolysaccharidosis VI. Vivizim was approved in 2014 and Naglazyme was approved in 2005. In one of 2023’s most highly anticipated FDA approvals, Sarepta Therapeutics’ Elevidys got approved in June as the first gene therapy for DMD targeting the underlying cause of the progressive genetic muscle-wasting disease, despite failing to meet the primary functional endpoint in a randomized trial. With a $3.2 million per patient price tag, Elevidys—developed and commercialized in partnership with Roche—also has the dubious distinction of being one of the world’s most expensive medicines. Sarepta CEO Doug Ingram told investors in Wednesday’s fourth quarter and full-year 2023 earnings call that the launch of Elevidys was “particularly impressive,” bringing in over $200 million in revenue since mid-2023, especially given that its label is “limited to four- and five-year-olds, representing only about 3% or so of the total Duchenne population.” The successful launch of Elevidys “shows that gene therapy can be commercially viable, providing hope for those patients with Duchenne, and for all those with genetic conditions with unmet needs,” Sarepta Chief Customer Officer Dallan Murray said during the call. However, Murray cautioned analysts to “not use this current younger population as a frame of reference for our market potential in the overall population.” At the end of last year, Sarepta submitted a supplemental BLA seeking to expand the gene therapy’s label by removing age and ambulation restrictions, while transitioning Elevidys from an accelerated to a traditional approval. The FDA has set a PDUFA date of June 21, 2024, and will not convene an advisory committee meeting to discuss the efficacy supplement to the BLA. “Hopefully, by July, we will have a broader label and we will be able to serve a much greater percentage of the [DMD] population,” Ingram said. Next, Sarepta should work on lowering the hefty price of Elevidys and ensuring equitable access to as many patients as possible who will benefit from the therapy. Greg Slabodkin is the News Editor at BioSpace. You can reach him at greg.slabodkin@biospace.com. Follow him on LinkedIn.

BioMarin is the subject of a probe by the U.S. Department of Justice, which has served the company with a subpoena requesting information on government-sponsored testing programs for enzyme replacement therapies Vimizim and Naglazyme. BioMarin has provided documents to the U.S. Department of Justice in response to a subpoena which requested information on the company’s government-sponsored testing programs for enzyme replacement therapies Vimizim and Naglazyme. The California biotech revealed the subpoena in a 10-K annual report that it filed on Monday. Both medicines are for the rare genetic condition mucopolysaccharidosis, a lysosomal storage disorder. Vimizim (elosulfase alfa) treats the Type IVA (Morquio A syndrome) version of the condition and has been on the market for 10 years. Naglazyme (galsulfase) treats Type VI (Maroteaux-Lamy syndrome) and was approved in 2005. "We have produced documents in response to the subpoena and are cooperating fully, but there is no assurance that such sponsored testing programs, or our other operations or programs, will not be found to violate" certain U.S. laws, the company said in the filing. The company warned that it may be required to pay penalties, be under increased government scrutiny or be suspended from participating in government healthcare programs if it is found in violation of privacy or data protection laws.  “This does not relate to the safety and efficacy of Vimizim and Naglazyme,” a BioMarin spokesperson said in an emailed statement. “While we have produced documents in response to the subpoena and are cooperating fully, we are still in early stages in responding to the subpoena and we currently cannot comment on any specific details.” The news made little impact on BioMarin's shares as their price has dropped by less than 1% since Monday morning. Both programs in question are for drugs that are among BioMarin’s best sellers. Vimizim generated sales of $701 million last year, while Naglazyme delivered $420 million in revenue. The duo combined for 46% of the company’s overall revenue last year of $2.42 billion.