UniQure on track for discussions with FDA on advancing AMT-130
Company seeking steps toward bid for therapy approval in Huntington’s
uniQure expects to begin planned discussions with the U.S. Food and Drug Administration (FDA) in the coming months to outline the future steps for testing its gene therapy candidate AMT-130 for early Huntington’s disease, and seeking regulatory approval of the treatment.
In its interactions with the FDA, expected to last all year, the company plans to discuss interim findings from two Phase 1/2 clinical trials ongoing in the U.S. (NCT04120493) and in Europe (NCT05243017) in adults with early Huntington’s.
“We are on track to initiate FDA interactions on AMT-130 this quarter and look forward to presenting longer-term follow-up data from our Phase [1/2] trials mid-year, which will include up to three years of patient follow-up on 29 treated patients,” Matt Kapusta, uniQure’s CEO, said in a company press release.
The company expects to provide an update on its regulatory plans in the next clinical update, set for mid-year, and to have a clearer idea of the potential path for AMT-130’s U.S. approval by year’s end.
Studies to date have shown that AMT-130 may successfully silence the gene whose mutations underlie the neurodegenerative disease.
AMT-130 now being tested in trials in US and Europe
Huntington’s occurs due to mutations in the HTT gene, which provides instructions for producing huntingtin, a protein that appears to be important for nerve cells to develop normally. This gene contains a group of three DNA building blocks, called a CAG repeat, that usually appears 10 to 35 times in a row.
In Huntington’s, CAG repeats are copied 36 times or more, resulting in an abnormal version of the huntingtin protein that is longer than usual and toxic to nerve cells. This can cause involuntary movements and a range of other symptoms, including problems with mental health and behavior.
AMT-130 uses a modified and harmless adeno-associated virus to deliver to cells a microRNA — a small piece of genetic material — that binds to the blueprints of the HTT gene to block the production of huntingtin, both its normal and mutated versions.
To target mostly nerve cells, the gene therapy is given as a one-time infusion deep into the brain as part of a surgical procedure. The treatment is expected to reduce the levels of mutated, toxic huntingtin in the brain, thereby easing symptoms and slowing their progression.
In the ongoing placebo-controlled Phase 1/2 trial in the U.S., 26 adults, ages 25-65, with early Huntington’s, received one of two doses of AMT-130 or a sham procedure. Participants are being followed for up to five years. After one year, those initially assigned the sham procedure may choose to receive AMT-130.
One-year interim data showed that AMT-130, given at a low or higher dose, halves the levels of mutated huntingtin in the cerebrospinal fluid, the liquid that flows around the brain and spinal cord.
Up to two years of data confirmed the favorable safety profile of both doses. Further, the data demonstrated that both doses helped patients maintain clinical and motor function relative to a group of untreated early Huntington’s patients participating in the observational TRACK-HD study.
A third group, to involve as many as 12 patients, is now being recruited in the U.S. trial. These participants are receiving immunosuppressive medications — specifically dexamethasone, sirolimus, and rituximab — before and after brain surgery to deliver AMT-130, given at a low or high dose.
This group is expected to be fully enrolled by the second half of the year, and the goal is to assess whether this approach effectively reduces the risk of adverse events among patients.
The Phase 1/2 trial in Europe has a similar design to the U.S. study, but all participants are treated with AMT-130. Six patients have been given the therapy’s low dose, and as many as nine are still being enrolled in the high-dose group.
By mid-year, uniQure expects to have, and discuss with the FDA, longer-term results collected over up to three years from a total of 29 patients who received either dose of the gene therapy in these trials. By that time, 21 treated patients will have at least two years of follow-up data.
The company also plans to consult with the FDA on using data on Huntington’s natural progression as a reference point relative to findings from clinical trials.
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