The FDA has set a Could 1 goal motion date beneath the Prescription Drug consumer Payment Act (PDUFA) for uniQure’s Huntington’s illness gene remedy candidate ifezuntirgene inilparvovec—which if authorised could be the primary therapy proven to change the deadly, inherited neurodegenerative dysfunction—after accepting the corporate’s Biologics License Software (BLA) beneath Precedence Evaluation. [uniQure]
The FDA has set a Could 1 goal motion date beneath the Prescription Drug Consumer Payment Act (PDUFA) for uniQure’s Huntington’s illness gene remedy candidate ifezuntirgene inilparvovec—which, if authorised, could be the primary therapy proven to change the deadly, inherited neurodegenerative dysfunction—after accepting the corporate’s Biologics License Software (BLA) beneath Precedence Evaluation.
The motion by the FDA, introduced Monday, marks an entire reversal of company opposition that surfaced final yr and hardened earlier this yr.
The FDA did warning uniQure, nevertheless, that it was tentatively planning to debate the BLA at a future advisory committee assembly, most certainly the Mobile, Tissue, and Gene Therapies Advisory Committee (CTGTAC). No date for such a gathering had been set at deadline, although uniQure stated it was instructed it will be notified by the company when that occurs.
uniQure submitted its BLA to the FDA in September, in addition to a Advertising Authorization Software (MAA) to the UK’s Medicines and Healthcare merchandise Regulatory Company (MHRA).
“The FDA’s acceptance of our BLA for evaluate marks an necessary milestone for the Huntington’s illness group, which has waited generations for a therapy that adjustments the course of this devastating illness,” uniQure CEO Matt Kapusta stated in a press release.
One analyst provided one more reason for the importance of the FDA motion: “We see the acceptance of the BLA as an necessary milestone for ifezuntirgene inilparvovec because it additional removes regulatory danger,” Lachlan Hanbury-Brown, analysis analyst, healthcare with William Blair, wrote in a analysis word.
Investor warning
Nevertheless, buyers appeared extra cautious, as uniQure shares dipped 3% to $24.03 as of 10:56 am. ET from $24.83 at Friday’s shut regardless of the optimistic information. Chatter on investor web sites advised a number of doable explanation why buyers have been reluctant to purchase uniQure inventory:
The PDUFA goal motion date was later than anticipated.
4-year information for the gene remedy confirmed decrease slowing of illness development than earlier three-year information.
Persevering with issues about danger within the ongoing trials.
Ifezuntirgene inilparvovec makes use of the corporate’s gene-silencing miQURE® platform and incorporates a microRNA designed to silence the huntingtin gene and the doubtless extremely poisonous exon 1 protein fragment. Sufferers obtain a single administration via focused, MRI-guided, convection-enhanced stereotactic neurosurgical supply immediately into the striatum (caudate and putamen).
uniQure has aligned with the FDA on what the corporate calls key components of the confirmatory examine design: The examine is being designed as a randomized, standard-of-care trial enrolling roughly 200 sufferers in a 2:1 ratio of ifezuntirgene inilparvovec to straightforward of care, with Complete Purposeful Capability (TFC) at 36 months serving as the first endpoint.
uniQure stated it plans to start affected person screening in america by the top of 2026.
Along with Precedence Evaluation, uniQure’s BLA for ifezuntirgene inilparvovec has been granted the FDA’s Breakthrough Remedy, Regenerative Drugs Superior Remedy (RMAT), and Quick Observe designations.
The FDA reversal follows a change in management on the Heart for Biologics Analysis and Analysis (CBER) as Vinayak (Vinay) Prasad, MD, who opposed uniQure’s BLA, resigned for the second time in March, efficient April 30. Prasad relinquished his roles as CBER director and FDA chief medical and scientific officer beneath Martin A. Makary, MD, who resigned efficient Could 12.
FDA stunner
Underneath Prasad, the FDA surprised uniQure in November 2025 when it instructed the corporate that what it had referred to as “game-changing” information in September, displaying vital slowing of HD development in sufferers handled with the gene remedy candidate, is probably not sufficient to safe FDA approval. The info prompted one analyst to foretell ifezuntirgene inilparvovec (then often known as AMT-130) would generate $4 billion peak worldwide annual gross sales by 2032, although a consensus of different analysts forecasted simply $1.7 billion in peak gross sales.
Key amongst uniQure’s Section I/II outcomes was the statistically vital 75% slowing of illness development as measured by the composite Unified Huntington’s Illness Ranking Scale (cUHDRS) at 36 months in sufferers handled with the excessive dose of 6×1013 gc/topic of ifezuntirgene inilparvovec, in comparison with a propensity score-matched exterior management derived from the Enroll-HD pure historical past database. That greater than met the first endpoint of the Section I/II examine, which consisted of trials in america (NCT04120493) and Europe (NCT05243017).
The FDA stepped up its public criticism in opposition to uniQure on March 2, when it issued what the corporate termed a “robust” suggestion to conduct a potential, randomized, double-blind, sham surgery-controlled examine to assist a future advertising and marketing utility for AMT-130. The FDA concluded that information from uniQure’s earlier Section I/II examine, which in contrast ifezuntirgene inilparvovec to an exterior management, weren’t adequate to supply the first proof of effectiveness wanted for the company to approve the gene remedy candidate.
UniQure inventory responded to the FDA jawboning by plummeting 42% on March 2 and three, then flattening in the course of that week, earlier than rebounding 58% by March 6. The inventory gyrations adopted Prasad asserting his resignation plans.
In June, with Karim Mikhail then serving as performing CBER director, the FDA reversed itself and accepted the three-year evaluation from the 2 Section I/II trials as the first foundation of a Biologics License Software (BLA) for accelerated approval of ifezuntirgene inilparvovec. Mikhail has since been appointed everlasting CBER director.
4-year information
Final month, uniQure reported optimistic four-year information for ifezuntirgene inilparvovec displaying a continued slowing of illness development based mostly on the 2 ongoing Section I/II research. At 48 months TFC, the first measure of uniQure’s confirmatory examine, confirmed constant slowing of useful decline, with absolute therapy profit maintained in Month 48. Variations seen between the excessive and low doses on each composite cUHDRS and TFC have been in step with a dose-dependent therapy impact, uniQure stated.
The first endpoint of cUHDRS confirmed a 44% slowing of illness development (non-significant p=0.144) whereas TFC confirmed a 61% slowing of illness development (nominal p=0.008), in keeping with uniQure.
“Whereas efficacy within the high-dose group as measured by the cUHDRS softened from yr 3 to yr 4 and thus might level to a weakening of therapy impact, we see issues from this endpoint as overdone given a number of caveats within the evaluation, and the truth that it isn’t the first endpoint of the confirmatory examine or the premise for the present BLA,” Hanbury-Brown commented.
“We consider the extra 48-month outcomes from the continuing Section I/II examine of AMT-130 in HD proceed to point out a optimistic scientific profit, particularly across the extra necessary regulatory endpoint of TFC, which elevated separation from the exterior management group from 3 to 4 years following therapy,” Hanbury-Brown added.
In its announcement Monday, uniQure stated the 2 trials have dosed 51 sufferers with ifezuntirgene inilparvovec. The U.S. randomized examine enrolled 26 sufferers, of which six obtained a low dose of ifezuntirgene inilparvovec, 10 a excessive dose, and 10 a sham process. 4 management sufferers subsequently crossed over to therapy after roughly 12 months.
The European open-label examine enrolled 13 sufferers—six receiving low-dose ifezuntirgene inilparvovec and 7, the excessive dose. A 3rd cohort of 12 sufferers explored each doses together with immunosuppression, whereas and a fourth cohort of six U.S. sufferers is evaluating the excessive dose in sufferers with decrease striatal volumes in comparison with these enrolled in earlier cohorts.
