Two dose-limiting toxicities have been recorded in uniQure’s trial evaluating an investigational AAV gene therapy designed to treat the rare condition Fabry disease.
In the phase 1/2 study, two patients receiving uniQure’s therapy, coded AMT-191, at a mid-level dose experienced asymptomatic Grade 3 liver enzyme elevations, according to a Feb. 6 company release.
Per protocol, uniQure has halted further dosing in the mid- and high-dose groups amid an ongoing assessment. Both impacted patients have responded to corticosteroid treatment.
No serious adverse events have been recorded at the two lower doses, but five were previously reported among two patients who received the third, highest dose. Two of those occurrences—chest pain and elevated troponin levels—were deemed related to AMT-191, and one has been potentially linked to the gene therapy.
“Given the positive efficacy signals but less clear safety profile, it will be interesting to see how well the lower dose continues to balance safety and efficacy,” analysts from Leerink Partners wrote in a Feb. 6 note.
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The phase 1/2a trial enrolled 11 patients across three dose levels. Patients at each level responded to treatment with elevated alpha-galactosidase A levels, and six of the 11 were able to discontinue enzyme replacement therapy, uniQure said. Investors have generally been pleased with the study’s results.
One of the trial’s goals is to determine the dosing for AMT-191 moving forward, uniQure said.
The AAV5-based gene therapy is designed to deliver a functional copy of the gene that makes alpha-galactosidase A, an enzyme critical for breaking down a type of lipid that otherwise builds up in patients’ tissues and blood vessels. In Fabry disease, toxic build-up of these lipids can lead to a range of symptoms, from numbness and pain to gastrointestinal trouble and hearing loss.
UniQure’s stock ticked up on Friday morning to a high of $27.74 per share, compared to the prior day’s close of $24.52. By 10:40 a.m. ET, the share price had normalized to $25.69.
The Leerink analysts expect attention to primarily remain on uniQure’s more high-profile Huntington’s disease program, which has received acclaim from experts for its efficacy but been met with pushback from the FDA. In November, the biotech called the agency’s about-face “a drastic change from the guidance” previously given.
Minutes from a type A meeting between uniQure and the FDA about the Huntington’s gene therapy will likely be released in late February or early March, the analysts noted.
