Cure Rare Disease Announces Patient Death in CRISPR Gene Therapy Trial of Duchenne

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Less than 2 months after the FDA gave Cure Rare Disease the go-ahead to proceed with its N-of-1 clinical trial (NCT0551429) assessing its CRISPR-based gene therapy, the company has announced that the primary patient in the study, Terry Horgan, has died.¹

It has not been made abundantly clear whether or not Horgan actually recieved the therapy before his death. Horgan is the brother of Cure Rare Disease founder Rich Horgan,who started the nonprofit to help identify a potential treatment for his brother, who was diagnosed with Duchenne muscular dystrophy (DMD) in 1999.

"We know the CRD-TMH-001 trial and the outcome have been closely followed by the rare disease community and many are eager for more details. While these details are currently being studied by multiple teams across the country, this is a complex undertaking and could take up to four months," Cure Rare Disease said in a statement.² "The comprehensive work these teams are doing is critical to gaining a clear understanding of the outcome of the CRD-TMH-001 trial and to shedding additional light on the challenges of gene therapy broadly."

The investigational therapy, CRD-TMH-001, is 1 of several therapeautic pursuits being supported by Cure Rare Disease, although it is the only one to have reached the clinical trial stage so far. It is designed to upregulate an alternate form of the dystrophin protein using CRISPR technology with the goal of stabilizing or potentially reversing, symptom progression of DMD. The nonprofit is currently exploring 19 different mutations associated with Duchenne and Becker muscular dystrophies, as well as several other pipeline candidates in limb girdle muscular dystrophy, adenylosuccinate synthase 1, and spinocerebellar ataxia.

The news is yet another bump in the road for the close-knit DMD community, who have become increasingly vocal proponents of investigational therapies coming before regulators. Several companies are working on therapeutics with DMD-related targets, but few have hedged big successes.

Most recently, Solid Biosciences presented new data on its gene therapy candidate SGT-001,³ which showed that treatment with the microdystrophin gene therapy was associated with improvements in stride velocity 95th centile at 1-year post-dose compared with baseline. Patients treated demonstrated an average improvement of 8.8%-9.5% from baseline, 23.9%-24.6% compared to natural history, and 26.0%-26.7% compared to the control patient. Solid plans to initiate clinical trial evaluation of another gene therapy candidate, SGT-003, in late 2023.

Further along in the process is Sarepta Therapeutics, who recently submitted a biologics license application to the FDA for the accelerated approval of SRP-001 (delandistrogene moxeparvovec), its gene therapy candidate for the treatment of ambulatory patients with DMD.⁴ The application is based on the expression of a shortened, functional version of the dystrophin protein as a surrogate end point that will likely result in clinical benefit. If accepted, Sarepta could expect a decision in May 2023.

REFERENCES
1. An update to the CRD community. News release. Cure Rare Disease. November 1, 2022. Accessed November 7, 2022. https://www.cureraredisease.org/blog-posts/update-to-crd-community
2. Cure Rare Disease Receives FDA Approval to Administer First-in-Human CRISPR Therapeutic. News release. Cure Rare Disease. August 9, 2022. Accessed November 7, 2022. https://www.cureraredisease.org/fda-approval
3. Solid Biosciences Presents New SGT-001 IGNITE DMD Study Results at World Muscle Society 2022 Congress Demonstrating Improvements in Ambulatory Function. News release. Solid Biosciences. October 13, 2022. Accessed November 7, 2022. https://www.solidbio.com/about/media/press-releases/solid-biosciences-presents-new-sgt-001-ignite-dmd-study-results-at-world-muscle-society-2022-congress-demonstrating-improvements-in-ambulatory-function
4. Sarepta Therapeutics Submits Biologics License Application for SRP-9001 for the Treatment of Ambulant Patients with Duchenne Muscular Dystrophy. News release. Sarepta Therapeutics. September 29, 2022. Accessed November 7, 2022. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-submits-biologics-license-application-srp