First person in FA FALCON trial receives SGT-212 gene therapy dose
Early safety data expected in coming months; study still enrolling participants
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The first patient has been dosed in a small study testing SGT-212, a gene therapy candidate being developed by Solid Biosciences for people with Friedreich’s ataxia (FA).
The dose-finding Phase 1b FALCON trial (NCT07180355) — a first-in-human study being conducted at two sites in the U.S. — is assessing SGT-212’s safety and tolerability in adults with FA. The trial is still recruiting up to 10 participants, ages 18-40. As an open-label study, both patients and researchers will know the exact medication being tested.
All participants will receive the treatment directly into a specific brain region, followed by intravenous, or into-the-vein, infusion.
The company shared in a press release that it expects to share preliminary safety data in the coming months, with an initial update by the second half of the year, depending on how fast enrollment goes.
“Initiating dosing in the FALCON trial represents the culmination of years of dedicated work [toward] moving the needle for the FA community,” said Bo Cumbo, Solid’s president and CEO.
In addition, the company announced that the U.S. Food and Drug Administration (FDA) granted orphan drug designation to SGT-212 for the treatment of FA. This designation confers incentives to develop therapies for rare diseases, defined in the U.S. as those that affect fewer than 200,000 people. Its perks include a waiver of FDA application fees and seven years of market exclusivity should the treatment be approved. This follows the FDA’s granting, last year, of rare pediatric disease designation and fast track status to SGT-212.
“Receiving orphan drug, fast track and rare pediatric disease designations underscores the significant unmet need the FA community faces and recognizes the therapeutic potential of SGT-212’s novel, dual-route administration,” Jessie Hanrahan, PhD, chief regulatory and preclinical operations officer at Solid, said in a separate press release, adding that the company is “[looking] forward to working closely with regulators to bring a potential new treatment option to the FA community.”
“We anticipate that the ability to leverage these regulatory designations will help streamline and potentially accelerate SGT-212’s development path,” Hanrahan added.
SGT-212 administered with help from real-time MRIs
Friedreich’s ataxia is caused by mutations in the FXN gene, which encodes frataxin, a protein essential for the proper functioning of mitochondria, the energy-generating cellular structures. The lack of functional frataxin leads to mitochondrial dysfunction, which particularly affects nerve and muscle cells, ultimately driving FA symptoms.
SGT-212 is a gene replacement therapy that uses an engineered adeno-associated virus to deliver a healthy version of the human FXN gene. The treatment aims to increase frataxin levels in nerve and heart cells, which, according to Solid, is expected to repair underlying mitochondrial dysfunction and address neurological, heart, and body-wide disease manifestations.
The therapy is first infused into the dentate nuclei in the cerebellum, a brain region involved in motor control and cognitive functions, via real-time MRI-guided administration. This allows doctors to confirm the targeted delivery of SGT-212 as it is administered.
We believe our novel, real-time, MRI-guided stereotactic [brain] delivery approach is one that truly embodies the promise of precision genetic medicine. … While these are early, single-participant observations, they strengthen our confidence in our targeted strategy and underscore our commitment to advancing paradigm-transforming treatments.
“We are ecstatic to report that intra-procedural MRI-imaging confirmed intradentate nuclei targeting and coverage that surpassed our expectations as well as thresholds we believe are necessary for a potential treatment effect,” Gabriel Brooks, MD, chief medical officer at Solid, said about the dosing of the first participant.
This is followed by intravenous infusion, which aims to increase frataxin levels in heart muscle cells and other tissues.
“We believe our novel, real-time, MRI-guided stereotactic [brain] delivery approach is one that truly embodies the promise of precision genetic medicine,” Brooks added. “While these are early, single-participant observations, they strengthen our confidence in our targeted strategy and underscore our commitment to advancing paradigm-transforming treatments.”
According to Cumbo, the company’s novel strategy sets its treatment apart — and aims to improve life quality for patients.
“By aiming to precisely target the key structures responsible for neurologic morbidity and cardiac manifestations, we intend to address both quality-of-life and mortality drivers in this devastating disease, a key differentiation of SGT-212 when compared to potential alternatives,” Cumbo said.
Solid hopes to get more patients involved in testing gene therapy
In a letter to the FA community shared on the company’s website, Annie Ganot, cofounder and head of patient advocacy at Solid, expressed appreciation to everyone who’s had a hand in the development of SGT-212.
“We are immensely grateful to the patients and families whose support, guidance and participation made this clinical study possible. Their trust, courage, time, and sacrifices help advance research for the entire FA community,” Ganot said.
Ganot also recognized the “extraordinary leadership and partnership” of the Friedreich’s Ataxia Research Alliance (FARA), noting that the nonprofit’s “ongoing guidance and support continue to shape and strengthen our clinical program.”
A key goal moving forward, Ganot said, is to get more FA patients involved in testing of SGT-212.
“While not all individuals who are interested will be able to participate in this initial trial, we hope to increase opportunities for participation over time through future study expansion and through continued community engagement that helps guide our progress,” Ganot said.
