Less than six weeks after uniQure announced that its gene therapy drug slowed the progression of Huntington’s disease by 75 percent over three years, the U.S. Food and Drug Administration (FDA) has backtracked on its conversations with the company regarding the timeline and data needed for potential approval of the remedy.
The company’s plan to apply for approval of the drug, AMT-130, in early 2026 and launch it into the market later that year may no longer be possible.
In a November 3 press release uniQure announced that, after a recent meeting with the FDA, the company believes that the “FDA currently no longer agrees” that data from its clinical trial of AMT-130 using an "external control" as a comparison "may be adequate to provide the primary evidence in support of” an application for approval.
The external control refers to data taken from Enroll-HD, the global HD patient registry of more than 22,200 people, as a baseline, rather than those taking a placebo, to compare with those on AMT-130. After extensive consultations with the FDA in 2024, uniQure had gotten permission from the agency to use the Enroll-HD data.
“This is a key shift from prior communications with the FDA in multiple … meetings over the past year,” the uniQure release stated. “Consequently, the timing of the BLA [Biologics License Application] submission for AMT-130 is now unclear.”
uniQure expects to receive the final minutes of its meeting with the FDA within 30 days and plans to urgently interact with the agency “to find a path forward for the timely accelerated approval of AMT-130,” the press release continued.
“We are surprised by the FDA’s feedback at the recent pre-BLA meeting, which is a drastic change from the guidance the FDA provided in November 2024,” said Matt Kapusta, the uniQure CEO. “This news is unexpected, and we are truly disappointed for people living with HD, who have no disease-modifying treatment options for this devastating disease.”
Kapusta added that “we strongly believe that AMT-130 has the potential to bring substantial benefit to patients, and we remain fully committed to working with the FDA to determine the best path forward to rapidly bring AMT-130 to patients and their families in the U.S.”
David Margolin, M.D., Ph.D., uniQure's vice president for clinical development, presents data illustrating AMT-130's slowing of the progression in Huntington's disease at the 20th Annual HD Therapeutics Conference, Palm Springs, CA, February 25, 2025 (photo by Gene Veritas, aka Kenneth P. Serbin).
FDA claims to ‘unleash gene therapies’
The October 30 Huntington’s Disease Society of America (HDSA) webinar on AMT-130, featuring uniQure’s chief medical officer, Walid Abi-Saab, M.D., offered no inkling of the FDA’s new position.
Some 1,000 people attended the webinar – a sign of the excitement about AMT-130 in the HD community. Reuniting after 17 years of estrangement, my own family has found great hope in the possibility of this treatment, though we understand that the drug is not a cure and might not even reach the public.
The FDA so far has provided no comment to the media on the matter. At the top of its website’s homepage it has the phrase “first six months of FDA reforms,” including “unleashing cell and gene therapies.”
As this blog reported in July, under the Trump administration the uncertainty of public funding for science has created serious challenges to HD research.
Politics and society play a role
Science and medicine do not act in a vacuum and are impacted by politics and society, as HD family member and historian Alice Wexler brilliantly illustrated in her book The Woman Who Walked into the Sea: Huntington’s and the Making of a Genetic Disease (click here to read my review).
In July, a New York Times report titled “Inside the Collapse of the FDA” detailed how Health and Human Services Secretary Robert F. Kennedy Jr., is “dismantling the agency.”
The key biotech and life sciences website STAT reported that since uniQure and the FDA had set drug submission “benchmarks” last year, “the agency has undergone considerable changes. Vinay Prasad, a physician with a reputation for taking a more conservative view of gene therapies, now oversees the division with authority over AMT-130.”
Dr. Prasad heads the Center for Biologics Evaluation and Research.
Only last week STAT reported that a “slow-boiling feud” between Dr. Prasad and his staff “is threatening the future of the center that regulates the nation’s vaccines, biological products, and blood supply.”
According to the report, officials in the center described it as “rife with mistrust and paranoia” and with fears of “retaliation” for pushing back on Dr. Prasad. The center has lost hundreds of employees this year to retirements, layoffs, and resignations. Dr. Prasad has also pushed out senior leaders, including “top cell and gene therapy regulators,” STAT reported.
Prasad has also played a role in limiting access to Covid-19 vaccines, according to STAT and the New York Times.
The HD community is ‘highly mobilized’
The scientist-written website HDBuzz noted that, although “the reason for the change of heart” of the FDA is “not currently clear,” “it makes the timeline for advancing AMT-130 less clear, with additional uncertainty as the U.S. government shutdown continues.”
“The decision by the FDA to not agree that an external control group can be used to apply for a [drug application] doesn’t change the data” of AMT-130’s actual effect in the clinical trial run by uniQure, HDBuzz stated. It simply means that the FDA would want to see more data, possibly from a trial designed with a placebo control group, before moving forward with a BLA for AMT-130.
HDBuzz also noted that uniQure is working with the equivalent of the FDA in the United Kingdom and Europe, with an approval there possibly leading to acceptance elsewhere.
HDBuzz stated that “we push forward – together.”
On November 5 HDSA and four other HD entities issued a joint statement: following the regulatory update about uniQure, “it’s clear that stronger alignment and collaboration among Huntington’s disease (HD) patient and family organizations are more critical now than ever.” The four are Huntington’s Disease Foundation (formerly Hereditary Disease Foundation), HD Reach, Help4HD International, and Huntington’s Disease Youth Organization.
“The next steps here are uncertain,” the brokerage and investment banking firm Stifel wrote, “but given the highly mobilized patient community in Huntington’s, and other external political forces that may have influence on the agency, the story here may not be over.”
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