FDA Grants Regenerative Medicine Advanced Therapy Designation to Laru-Zova for X-Linked Retinitis Pigmentosa

The FDA granted regenerative medicine advanced therapy (RMAT) designation to laruparetigene zovaparvovec (laru-zova; Beacon Therapeutics Holdings Ltd) for the treatment of X-linked retinitis pigmentosa (XLRP). RMAT is intended to expedite the development and review of regenerative medications that have the potential to address unmet needs for serious or life-threatening diseases.¹

The designation is based on preliminary clinical data from the phase 2 DAWN (NCT06275620) and SKYLINE (NCT06333249) trials.| Image Credit: blackday | stock.adobe.com

"The FDA's decision to grant RMAT designation to laru-zova is a significant milestone for the XLRP patient community and underscores our promising data and the potential for laru-zova to significantly improve the lives of patients who suffer from XLRP," Lance Baldo, MD, CEO of Beacon Therapeutics, said in a news release. "We look forward to working closely with the FDA on continued development activities to support an expedited pathway for laru-zova."¹

The designation is based on preliminary clinical data from the phase 2 DAWN (NCT06275620) and SKYLINE (NCT06333249) trials, which evaluated the safety, efficacy, and tolerability of the drug in patients with XLRP with the RPGR gene.¹

The DAWN trial is an open-label multicenter study to evaluate the safety of 2 doses of laru-zova administered as a single subretinal injection for patients who were previously treated with full-length adeno-associated virus vector-based gene therapy. Individuals included in the study were treated with a single subretinal injection of 1 of 2 dose levels in their previously untreated eye. There were 3 groups, with group 1 including 12 individuals for the high dose, group 2 including 6 individuals with the low dose, and group 3 with approximately 3 to 6 individuals. If no safety signals were identified, group 3 would receive a single high dose of the drug.²

In the 3-month data, investigators found that laru-zova was well tolerated in all patients, with no agent-related treatment-emergent adverse events (TEAEs) reported, including no ocular inflammatory adverse events. Data also showed early improvements in low luminance visual acuity, according to a news release.³

In the SKYLINE trial, investigators evaluated the safety and efficacy of the drug in approximately 12 patients that were not part of the phase ½ HORIZON study. Patients received randomized treatment in a 1:1 ratio for either the low dose or the high dose, according to the clinical trial information.The 24-month data showed that the response rate was 57% (4 of 7 individuals) for those treated with the high dose. For the low dose, the response rate was 25% (1 of 4 individuals). Further, there were no clinically significant safety events associated with the drug, and TEAEs were mostly non-serious and mild to moderate in severity.^4,5

Laru-zova was also granted 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 United Kingdom. Currently, enrollment is ongoing for the phase 2/3 VISTA (NCT04850118) trial.¹

REFERENCES

1. Beacon Therapeutics granted FDA regenerative medicine advanced therapy (RMAT) designation for laru-zova (AGTC-501). News release. Beacon Therapeutics. January 28, 2025. Accessed January 30, 2025. https://www.prnewswire.com/news-releases/beacon-therapeutics-granted-fda-regenerative-medicine-advanced-therapy-rmat-designation-for-laru-zova-agtc-501-302361416.html

2. A Study Comparing Two Doses of AGTC-501 in Male Participants With X-linked Retinitis Pigmentosa Caused by RPGR Mutations (DAWN). ClinicalTrials.gov identification: NCT06275620. Updated October 30, 2024. Accessed January 30, 2025. https://clinicaltrials.gov/study/NCT06275620

3. Beacon Therapeutics announces positive 3-month data from phase 2 DAWN trial of laru-zova (AGTC-501) in patients with X-linked retinitis pigmentosa (XLRP). News release. Beacon Therapeutics. December 6, 2024. Accessed January 30, 2025. https://www.prnewswire.com/news-releases/beacon-therapeutics-announces-positive-3-month-data-from-phase-2-dawn-trial-of-laru-zova-agtc-501-in-patients-with-x-linked-retinitis-pigmentosa-xlrp-302324627.html

4. A Study Comparing Two Doses of AGTC-501 in Male Subjects With X-linked Retinitis Pigmentosa Caused by RPGR Mutations (SKYLINE). ClinicalTrials.gov identification: NCT06333249. Updated August 12, 2024. Accessed January 30, 2025. https://clinicaltrials.gov/study/NCT06333249

5. Beacon Therapeutics announces positive 24-month data from phase 2 SKYLINE trials of laru-zova (AGTC-501) in patients with X-lined retinitis pigmentosa. News release. October 15, 2024. Accessed January 30, 2025. https://www.beacontx.com/news-and-events/beacon-therapeutics-announces-positive-24-month-data-from-phase-2-skyline-trial-of-agtc-501-in-patients-with-x-linked-retinitis-pigmentosa/