Huntington Disease Gene Therapy Nets RMAT Designation

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AMT-130 has shown some evidence of dose-dependent clinical benefits in treated study participants.

The FDA has granted Regenerative Medicine Advanced Therapeutic (RMAT) Designation to uniQure’s AMT-130 gene therapy for the potential treatment of Huntington disease (HD).1

“We’re thrilled to receive the first ever RMAT designation for an investigational therapy for HD,” Matt Kapusta, chief executive officer, uniQure, said in a statement.1 “This achievement is a significant milestone for the program and supports the potential for AMT-130 to address the high unmet medical need of those suffering from this devastating disease.”

AMT-130 is an adeno-associated virus (AAV5) vector gene therapy that delivers an artificial micro-RNA designed to silence the huntingtin gene and therefore inhibit the production of mutant huntington protein. The therapy was developed with the use of uniQure’s proprietary miQURE™ silencing technology.

“The RMAT designation, which was based on the comparison of the 2-year AMT-130 data to a natural history cohort, marks a promising start to our FDA interactions,” Walid Abi-Saab, chief medical officer, uniQure, added.1 “Importantly, RMAT designation allows for increased collaboration with the FDA to accelerate development, potentially facilitating earlier access for patients with life-threatening medical conditions.I’m incredibly proud of the team atuniQure for this accomplishment, and we look forward to presenting updated interim data from our ongoing Phase I/II studies in the middle of the year.”

READ MORE: FDA Recognizes BlueRock’s Parkinson Disease Cell Therapy With RMAT Designation

uniQure shared data from the program in December 2023 that demonstrated some evidence of preserving neurological function and dose-dependent clinical benefits. The data, current as of September 30, 2023, were from 30 months of follow-up of 39 patients enrolled in the US (n = 26) and European trials (n = 13) of AMT-130. The participants were randomized to treatment with AMT-130 administered by stereotactic neurosurgical delivery procedure or an imitation (sham) surgery. The US trial had a low dose (6 treated, 4 control) and high dose (10 treated, 6 control) cohort and the European trial had a low dose (n = 6) and high dose (n = 7) cohort.

Treated participants experienced some dose-dependent clinical benefits, with improvements in neurological function in the high dose cohort and preserved neurological function in the low dose cohort. On the composite Unified HD Rating Scale the low dose cohort (6x1012 vg) had a difference of 0.39 points at 30 months from baseline and the high dose (6x1013 vg) cohort had a difference of 1.24 points at 18 months, compared with baseline values of 14.1 and 14.9, respectively. On the Total Functional Capacity scale the low dose cohort had a difference of 0.95 points at 30 months and the high dose cohort had a difference of 0.49 points at 18 months compared with baseline values of 11.9 and 12.2, respectively. On Total Motor Score scale, the low dose cohort had a difference of 2.80 points at 30 months and the high dose cohort had a difference of 1.70 points at 18 months compared with baseline values of 13.3 and 12.1, respectively.

“The clinical assessment trends in the ongoing studies of AMT-130 look very promising and continue to show disease stability in Huntington’s disease patients treated with this one-time administered gene therapy, several of whom have now been followed more than 2 years,” Walid Abi-Saab, MD, chief medical officer, uniQure, said in a statement at that time.2 “We are observing favorable trends in evaluation of motor skills, functional independence, and composite rating scores as compared to a non-concurrent criteria-matched natural history cohort.”

REFERENCES
1. uniQure Receives FDA Regenerative Medicine Advanced Therapy (RMAT) Designation for Investigational Gene Therapy AMT-130 in Huntington’s Disease. News release. June 3, 2024. https://www.globenewswire.com/news-release/2024/06/03/2892124/0/en/uniQure-Receives-FDA-Regenerative-Medicine-Advanced-Therapy-RMAT-Designation-for-Investigational-Gene-Therapy-AMT-130-in-Huntington-s-Disease.html
2. uniQure Announces Update on Phase I/II Clinical Trials of AMT-130 Gene Therapy for the Treatment of Huntington’s Disease. News release. UniQure. December 19, 2023. https://www.globenewswire.com/news-release/2023/12/19/2798425/0/en/uniQure-Announces-Update-on-Phase-I-II-Clinical-Trials-of-AMT-130-Gene-Therapy-for-the-Treatment-of-Huntington-s-Disease.html
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