UniQure recently announced the enrolment of the first two patients in the second cohort of a Phase I/II clinical trial of AMT-130, a micro ribonucleic acid (miRNA) gene therapy, in development for Huntington’s disease (HD). Considering the pressing need for a DMT and the limited pipeline candidates, AMT-130 will have a great opportunity to become a game changer for HD in the next ten years if it is deemed effective in trials, says GlobalData, a leading data and analytics company.

Though this is a promising step towards advancing the development of this disease-modifying therapy (DMT) in a disease with significant unmet clinical need, AMT-130 still has a long and challenging road to prove its safety and impact on modifying HD progression, while also tackling the anticipated high cost of the treatment.

Sarah Elsayed, Neurology Analyst at GlobalData, comments: “UniQure’s announcement comes at an opportune time, with the HD community eagerly awaiting the development of a potential DMT following the failure of three promising candidates in Phase II trials last March— namely Roche’s gene therapy, tominersen and Wave’s antisense oligonucleotides, rovanersen and lexanersen.

“With only Teva’s Austedo (deutetrabenazine) and tetrabenazine, currently approved for the symptomatic treatment of HD-associated chorea, establishing effective and safe treatments for HD has proved particularly challenging for drug developers for several reasons. The imperfect animal models, which are used in the preclinical phase to test new interventions, are not a good mimic of the more-prevalent adult-onset HD, leading to a high failure rate for drug development. Several candidates that previously showed promise in animal models were not able to translate to a reduction in mutant huntingtin (HTT) gene in larger human brains.”

Key opinion leaders (KOLs) interviewed by GlobalData noted that patient enrolment has proved to be difficult in HD, due to the rarity of the disease and the need to particularly recruit premanifest or early-stage patients for trials investigating DMTs. Therefore, UniQure has laid a good foundation for AMT-130, by already achieving progress in the enrolment process.

Additionally, the therapy has secured both orphan drug designation and fast-track designation by the Food and Drug Administration (FDA) in 2017 and 2019, respectively. This allows for frequent meetings with the FDA and the independent safety board regarding the clinical study design, which will be an additional advantage for UniQure, considering the repeated failures in trials of other gene pipeline agents.

Elsayed adds: “AMT-130 therapy is believed to decrease the accumulation of the huntingtin protein, the underlying cause of the HD disease. The therapy requires a single brain procedure. KOLs indicated that this mechanism of action and route of administration look robust yet cautiously promising as the drug is still undergoing early stages of clinical development. However, the HD market that was valued at $245m in the US in 2020, is not expected to see any drastic changes over the next ten years. As such, UniQure appears well-positioned to enter the HD market with AMT-130 as any drug that succeeds to demonstrate clinical benefits in altering or halting the disease progression, is expected to command an exponential market uptake.”