UniQure Pauses High Dose of AMT-130 Huntington Disease Gene Therapy for Severe Adverse Events


No such adverse events have occurred in the lower-dose group.

Following the report of promising 12-month data for the lower-dose cohort in the Phase 1/2 study of gene therapy AMT-130 for the treatment of Huntington disease, UniQure has announced that it has since paused enrollment in its higher-dose cohort due to the occurrence of suspected unexpected severe adverse reactions (SUSARs).

The pause in enrollment is pending a safety review by the independent Data Safety Monitoring Board, which is expected to take place in Q4 of this year. Enrollment in the lower-dose cohort continues, as the company also plans to start crossing over control patients in Q3 2022.

The SUSARs consisted of localized inflammatory responses and other related symptoms observed in 3 patients treated with the higher dose of AMT-130; 2 patients from a single clinical site in the European cohort and 1 patient in the US cohort. Notably, the US-based patient's symptoms, which occurred following treatment in March 2022, were originally deemed unrelated to the therapy but a consequence of the procedure, which involves administering AMT-130 into the striatum of the brain through 2 to 6 small holes in the skull via micro-catheter. Following the European SUSAR reports in July, UniQure reclassified and reported the event as a SUSAR.

“While these patients have fully or substantially recovered, and no clear root cause has yet been identified, we believe it’s prudent to temporarily delay additional higher-dose procedures until we put additional monitoring and treatment plans in place and complete our safety review early in the fourth quarter of 2022," said UniQure chief executive officer Matt Kapusta in a statement. "The delay is not expected to impact any future lower-dose procedures, as no serious adverse events related to AMT-130 have been reported in any of the additional 12 patients treated at the lower dose, and no impact is expected on the timing of previously guided data read-outs in 2023, including the presentation of 1 to 2-year follow-up on both low and high-dose cohorts in the second quarter of 2023.”

The company previously reported encouraging 12-month data from the US-based lower-dose cohort, noting that the treatment was generally well-tolerated with no serious adverse events reported that were deemed related to treatment. Among the 12 patients treated, 4 with evaluable data showed a decline in mutant Huntingtin protein (mHTT) in cerebrospinal fluid at all timepoints compared with baseline, culminating in a mean 53.8% decrease at 12-month follow-up. This is compared with control patients, 3 of whom with available data showed an increase in mean mHTT at 1, 3, 6 and 9 months, ultimately with a mean decrease of 16.8% at 12-month follow-up.

In addition, 6 patients' neurofilament light chain (NfL) neared baseline levels at 12-month follow-up after an expected increase following the treatment procedure. At 12 months, a mean increase in NfL of 8% compared with baseline was recorded, with 2 of 6 patients having levels at or below baseline at 12-month follow-up, and 1 patient's levels falling below baseline at 15- and 18-month follow-up.

UniQure plans to present 1- to 2-year follow-up data from the US cohort in Q2 2023, with 1-year data from the European low-dose cohort planned in 2023, as well.

uniQure Announces Second Quarter 2022 Financial Results and Highlights Recent Company Progress. News release. UniQure. August 8, 2022. https://www.globenewswire.com/news-release/2022/08/08/2493736/0/en/uniQure-Announces-Second-Quarter-2022-Financial-Results-and-Highlights-Recent-Company-Progress.html

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