A uniQure gene remedy for Huntington’s illness has interim knowledge exhibiting the one-time therapy slows development of this uncommon neurodegenerative dysfunction that has no FDA-approved therapies. Based mostly on these encouraging knowledge, the corporate stated Tuesday it now plans to debate with regulators the potential for a quicker scientific and regulatory path ahead.
Huntington’s stems from a genetic mutation that results in irregular variations of the huntingin protein. The illness results in motor dysfunction, behavioral modifications, and cognitive decline. The uniQure gene remedy, code-named AMT-130, makes use of an engineered virus to ship microRNA that silences the huntingin gene and the poisonous protein fragment that drives the illness.
Amsterdam-based UniQure is evaluating AMT-130 in a sham-controlled Part 1/2 sham scientific trial within the U.S. and Europe. After a blinded 12-month interval, research contributors might be adopted unblinded for 5 years. The research are meant to find out which dose of AMT-130 to advance to pivotal testing.
The interim outcomes introduced Tuesday are from as much as 24 months of follow-up in 21 handled sufferers. A complete of 12 sufferers obtained the low dose and 9 obtained the excessive dose as of the March 31 cutoff date. Utilizing a composite scale used to evaluate Huntington’s development, these sufferers had been in contrast with an exterior management developed utilizing knowledge from pure historical past research.
In response to uniQure, outcomes to this point present a statistically important 80% slowing of illness development in sufferers who obtained the excessive dose; 30% slowing of illness development in these given the low dose. UniQure stated the excessive dose group confirmed stability of motor and cognitive operate that was close to baseline ranges all through the 24 months of follow-up.
One other purpose of the research is measuring cerebral spinal fluid ranges of neurofilament mild protein (NfL), proteins which are considered an indicator of neurodegenerative illness. There’s precedent for utilizing NfL ranges as a biomarker in neurological illness scientific trials. Qalsody, an amyotrophic lateral sclerosis drug developed by Biogen, obtained accelerated FDA approval final 12 months based mostly partially on scientific knowledge indicating a decreasing of NfL ranges within the blood. Within the AMT-130 research, uniQure reported a statistically important decreasing of NfL ranges in comparison with baseline. To this point, the gene remedy has been properly tolerated by sufferers with no reviews of significant antagonistic occasions.
“These up to date outcomes are thrilling and supply compelling proof of potential therapeutic profit,” Dr. Victor Sung, professor of neurology on the College of Alabama at Birmingham (UAB), and director of the UAB Huntington’s Illness Clinic, stated in a ready assertion. “The preservation of motor and cognitive operate noticed via two years, mixed with decreased NfL ranges under baseline, defy expectations in regards to the pure development of Huntington’s illness.”
Based mostly on these interim knowledge, uniQure stated it plans to satisfy with the FDA later this 12 months to debate expedited scientific growth of the remedy, together with a possible pathway for accelerated approval. In a notice despatched to buyers final week, William Blair analyst Sami Corwin wrote that FDA suggestions on the regulatory path for AMT-130 is essential, as it would present readability on the viability of an accelerated approval. This pathway may use surrogate biomarkers similar to measures of NfL. UniQure additionally wants to listen to whether or not the company’s Heart for Biologics Analysis and Analysis (CBER) would require a placebo-controlled scientific trial or if a pure historical past or exterior comparator arm will suffice as a management.
“Current commentary from Peter Marks, M.D., Ph.D., the director of CBER, signifies that the division will look to more and more use accelerated approval pathways and extra versatile pivot trial designs for gene therapies, which we imagine may very well be a tailwind for uniQure because it begins regulatory discussions from AMT-130,” Corwin stated.
UniQure stated a 3rd cohort within the U.S. portion of the Part 1/2 research is predicted to finish enrollment within the second half of this 12 months. This group is evaluating the gene remedy together with immunosuppression. UniQure anticipates security knowledge from this group might be prepared within the first half of subsequent 12 months. By mid-2025, uniQure anticipates presenting one other interim evaluation from the Part 1/2 trial, this time with 36 months of knowledge.
Buyers welcomed the interim outcomes. Shares of uniQure soared greater than 70% in buying and selling on Tuesday.
Photograph: Yuichiro ChinoImage, Getty Photos
