On 24 September, uniQure announced positive topline results from its pivotal Phase I/II studies (HD-GENE-TRX1, HD-GENE-TRX2) for its novel gene therapy AMT-130 in Huntington’s disease (HD). At 36 months, high-dose AMT-130 demonstrated a statistically significant 75% disease slowing measured by the composite Unified Huntington’s Disease Rating Scale compared with a propensity-matched external control. A key secondary endpoint of a statistically significant slowing of disease progression measured by total functional capacity was also met at 36 months.
In a market where the only available therapies are for the symptomatic management of chorea, the efficacy results of AMT-130 are unprecedented. Key opinion leaders (KOLs) previously interviewed by GlobalData consistently highlighted the significant unmet need in the HD market for a therapy that can modify the disease, and slow or prevent progression, with AMT-103 poised to become the first treatment option for HD that meets this need. Based on previously announced data at 24 months, many KOLs had highlighted AMT-130 as particularly promising, being impressed by the data up to that point. uniQure announced plans to submit a biologics license application to the US Food and Drug Administration in the first quarter of 2026, and with previously granted orphan drug, fast-track, and regenerative medicine advanced therapy designations, approval in the US could be expected as early as the second half (H2) of 2026.
However, despite the significant results for AMT-130, barriers remain for uptake of the gene therapy, if approved. Firstly, as a gene therapy, AMT-130 is expected to be extremely expensive, which may pose reimbursement and access challenges for patients. Additionally, AMT-130 requires invasive, complex, magnetic resonance imaging-guided, convection-enhanced stereotactic neurosurgical delivery, which not all patients may be eligible for or want to undergo. This cumbersome route of administration will also pose a significant operational burden for AMT-130. Further, once the gene therapy has been administered it cannot be removed and despite being well tolerated with no serious adverse events observed since the trial was temporarily paused in 2022 and additional monitoring procedures were put in place following the neurosurgery, some KOLs remained cautious about the longer-term safety of a gene therapy given the pivotal trials have only enrolled a small number of patients, with only 12 patients in the high-dose AMT-130 group having reached the 36 month point thus far.
As AMT-103 will likely not be available for all patients with HD, space remains for other developers pursuing alternative, potentially disease-modifying options for HD. Roche and Wave Therapeutics are both developing an antisense oligonucleotide for HD, and PTC Therapeutics/Novartis and Skyhawk Therapeutics are developing oral drugs targeting the huntingtin protein. KOLs were in favour of having a range of options for patients with HD, with many KOLs noting that if an oral drug could demonstrate significant efficacy, it would face the fewest access barriers for patients. Overall, GlobalData expects significant growth in the HD market over the next ten years, with uniQure’s AMT-130 having blockbuster potential.