The FDA has granted Regenerative Medicine Advanced Therapy (RMAT) designation to two gene therapies targeting different forms of retinitis pigmentosa (RP), a group of inherited retinal diseases that cause progressive vision loss. These designations aim to accelerate the development and review of these therapies, addressing significant unmet needs in patients with advanced-stage RP and X-linked retinitis pigmentosa (XLRP).
Bionic Sight's BS01 for Advanced Retinitis Pigmentosa
Bionic Sight, Inc. announced that its investigational gene therapy, BS01, received RMAT designation for treating RP patients with advanced vision loss. The designation was based on preliminary data from an ongoing Phase 1/2 clinical trial (NCT04278131). The open-label, dose-escalation study assessed the safety and efficacy of BS01 in patients with advanced-stage RP.
Preliminary results from the Phase 1/2 trial indicated that participants receiving lower doses of BS01 showed a modest but consistent improvement. Specifically, 5 out of 5 participants demonstrated a 100-fold or greater increase in light sensitivity, with several also gaining the ability to detect motion. Participants receiving higher doses showed more marked improvements. Ten of 11 patients showed an increase in visual acuity (Best Corrected Visual Acuity, BCVA), with 7 patients showing an average increase of nearly 5 lines (4.7 lines) on the EDTRS eye chart. These improvements were observed across a spectrum of patients, from those with baseline vision at the "count fingers" level to those with "tunnel vision" (less than 10 degrees of visual field).
In addition to BCVA improvements, patients who could initially only "count fingers" gained the ability to recognize shapes, objects, and in some cases, colors. Patients with tunnel vision showed both an increase in visual field size (a 3-fold increase in area) and a pronounced improvement in their ability to navigate a maze, measured by a reduction in completion time and errors. The remaining 3 high-dose patients, who had baseline vision at the "light perception" level, improved to "hand motion." BS01 was well-tolerated, with no product-related serious adverse events reported; all events were grade 1 or 2 and generally asymptomatic.
Calvin Roberts, MD, President and CEO of the Lighthouse Guild, stated that the RMAT designation is a significant validation of Bionic Sight’s BS01 therapy, given the intensity of the FDA review process on both safety and efficacy data. He added that the company has potentially game-changing results for people with RP and the potential to have similar results for other retinal degenerative diseases as well.
Beacon Therapeutics' Laru-zova for X-Linked Retinitis Pigmentosa
Beacon Therapeutics also announced that its gene therapy, laruparetigene zovaparvovec (laru-zova), received RMAT designation for the treatment of X-linked retinitis pigmentosa (XLRP). The FDA's decision was based on initial clinical evidence from the Phase 2 DAWN (NCT06275620) and SKYLINE (NCT06333249) trials, which are assessing the safety, tolerability, and efficacy of laru-zova in XLRP patients with mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene.
Laru-zova is designed to express the full-length RPGR protein, addressing the extensive photoreceptor damage in XLRP. There are currently no available treatments for XLRP, which primarily affects young males, with an estimated prevalence of 1 in 25,000 males in the US, Europe and Australia having XLRP with RPGR mutations.
Data from the DAWN trial demonstrated improvements in low luminance visual acuity (LLVA). Laru-zova also holds Fast Track designation from the FDA, PRIME designation from the European Medicines Agency, and ILAP designation from the Medicines and Healthcare Products Regulatory Agency in the UK.
Lance Baldo, MD, chief executive officer of Beacon Therapeutics, stated that the FDA’s decision to grant RMAT designation to laru-zova is a significant milestone for the XLRP patient community, and underscores the promising data and the potential for laru-zova to significantly improve the lives of patients who suffer from XLRP. He added that they look forward to working closely with the FDA on continued development activities to support an expedited pathway for laru-zova.
Implications of RMAT Designation
The RMAT designation, created as part of the 21st Century Cures Act, is intended to expedite the development and review of regenerative medicine therapies for serious medical conditions. It includes all the benefits of the fast track and breakthrough therapy designation programs, including early interactions with the FDA, but is specified for regenerative medicine therapies. This designation allows for enhanced communication with the FDA throughout development, the opportunity to discuss appropriate endpoints to support accelerated approval, and eligibility for expedited programs such as priority review. Both Bionic Sight and Beacon Therapeutics are now positioned to potentially accelerate the development and approval of their respective gene therapies for retinitis pigmentosa.
