Solid Biosciences' CPVT Gene Therapy SGT-501 Cleared for Phase 1b Trial

Solid Biosciences' SGT-501, an investigational adeno-associated virus (AAV) vector-based gene therapy intended to treat catecholaminergic polymorphic ventricular tachycardia (CPVT), has received clearance of an investigational new drug (IND) application by the FDA and a clinical trial application by Health Canada.¹

In light of the clearances, the company plans to launch a phase 1b clinical trial in the final quarter of this year. SGT-501 is intended to address CPVT by providing a full-length, codon-optimized copy of the cardiac calsequestrin (CASQ2) gene to the muscle cells of the heart. Increase in the production of the CASQ2 protein is expected to stabilize the ryanodine receptor (RYR2) via improved buffering of free calcium in sarcoplasmic reticulum. According to Solid, stabilization of RYR2 is in turn expected to help maintain normal cardiac rhythm and may help protect patients from ventricular tachycardia.

“Despite being identified nearly 50 years ago, CPVT still lacks FDA-approved therapies – this announcement reflects a critical development in the treatment of this underserved, often fatal, cardiac disease,” Gabriel Brooks, MD, the chief medical officer of Solid, said in a statement.¹ “SGT-501 offers a precision genetic approach targeting the underlying pathophysiology of the disease: abnormal calcium releases from the sarcoplasmic reticulum in an otherwise structurally sound heart. We believe SGT-501 has the unique potential to provide durable protection and may be capable of liberating patients from the ever-present threat of lethal arrhythmias and life-limiting prohibitions on exercise. Solid is proud to launch this program to help address this clear unmet need, further expanding our pipeline of differentiated and thoughtfully designed genetic medicines.”

SGT-501's AAV-CASQ2 gene therapy approach was initially developed by investigators in the IRCCS ICS Maugeri lab in Pavia, Italy, including Silvia Priori, MD, PhD, a professor of cardiology at the University of Pavia and the director of the Molecular Cardiology Unit at the IRCCS Maugeri, and in-licensed by Solid Biosciences in 2023. Notably, SGT-501 previously has previously been granted both orphan drug designation and rare pediatric disease designation by the FDA.

“After decades during which we, the clinical community, have been limited in our ability to treat people living with CPVT, I have long hoped for the day when a genetic-modifying therapy becomes available,” Priori added to the statement.¹ “We are proud to partner with Solid who advanced fundamental work from our labs at Maugeri, which demonstrated the principle that calsequestrin overexpression can have a therapeutic impact on multiple forms of CPVT in both cellular and mouse models of disease. This work was further developed into a compelling IND safety and efficacy package through close collaboration with, and studies conducted by, the Solid team. I look forward to clinical updates for SGT-501 and seeing how this potential medicine may benefit people living with CPVT who are in critical need of disease-specific medicines.”

In addition to SGT-501, Solid is developing a number of other gene therapy products for various indications. Earlier this year, the company reported data from the phase 1/2 INSPIRE DUCHENNE clinical trial (NCT06138639) evaluating SGT-003, an investigational next-generation AAV vector-based gene therapy, for the treatment of Duchenne muscular dystrophy (DMD).² The efficacy set for the interim data announced by the company included 2 boys who were 5 years of age at the time of dosing and 1 boy who was 7 years of age at the time of dosing. As of 90 days posttreatment, the 3 boys showed microdystrophin expression at mean levels 110% of normal according to Western blot and at mean levels 108% of normal according to mass spectrometry. Notably, CGTLive® previously covered the design of the INSPIRE DUCHENNE trial as part of our Clinical Trials in Progress series. The first-in-human study, which takes the form of an open-label, nonrandomized trial, was initiated on May 6, 2024 and is expected to enroll an estimated 43 patients aged 4 to 11 years. Participants receive a single dose of SGT-003, at 1x10¹⁴ vg/kg, via intravenous infusion.

REFERENCES
1. Solid Biosciences announces FDA IND and Health Canada CTA approval for first-in-class cardiac gene therapy to treat catecholaminergic polymorphic ventricular tachycardia (CPVT). News release. Solid Biosciences Inc. July 8, 2025. Accessed July 10, 2025. https://investors.solidbio.com/news-releases/news-release-details/solid-biosciences-announces-fda-ind-and-health-canada-cta
2. Solid Biosciences reports positive initial clinical data from next-generation Duchenne gene therapy candidate SGT-003. News release. Solid Biosciences Inc. February 18, 2025. Accessed July 10, 2025. https://investors.solidbio.com/news-releases/news-release-details/solid-biosciences-reports-positive-initial-clinical-data-next