Two key political developments could aid uniQure’s effort to seek approval of its historically efficacious Huntington’s disease gene therapy, AMT-130, from the U.S. Food and Drug Administration (FDA): a senatorial probe of the FDA and a letter to President Trump from rare-disease advocates.
As reported widely, uniQure is preparing for yet another meeting with the FDA to discuss the potential Phase III large-scale clinical trial required by the agency to further test the efficacy of AMT-130. Since its start in 2019, the Phase I/II trial has involved some 45 people. In September 2025, uniQure revealed that 17 of the individuals receiving the highest dose of AMT-130 had a slowing of progression of HD by 75 percent. The FDA, seen by many biotech observers to have become dysfunctional under the Trump administration, then surprisingly reneged on a promise to allow uniQure to apply for approval in 2026.
On March 9, Wisconsin Sen. Ron Johnson, a Republican, announced that he had launched an investigation of the FDA because it had rejected drug applications for several rare diseases.
Senator Ron Johnson (official congressional photo)
Johnson described the FDA’s request for a new AMT-130 trial, which would include a deeply invasive sham surgery for participants not getting the actual drug, as “bureaucratic idiocy.”
AMT-130 requires a twelve-hour surgery to inject the drug deep into the brain. The sham surgery would serve as a placebo in the clinical trial.
“You’re expecting people to go through sham surgeries where they get holes drilled in their heads?” Johnson said. “That’s just unbelievable.”
As part of his probe, Johnson is seeking denial letters from the FDA. Referring to the agency, he said that the “stories are outrageous. It just appears that they’re looking for excuses to say no.”
The senator added: “We’re going to find out exactly what issues the FDA listed for their ‘nos’.”
A sham surgery could pose ‘significant risk’
Johnson’s office did not respond to my request for an interview.
Walid Abi-Saab, M.D., uniQure’s chief medical officer, told the key publication Neurology Today that a sham controlled study “could impose significant risks and burden to patients” and that some people may consider it unethical.
Dr. Abi-Saab added that volunteers facing the sham surgery could not access other potentially disease-modifying therapies advancing through trials involving several years of observation.
Early in the AMT-130 program, uniQure used a sham surgery in several individuals but then stopped precisely because of ethical concerns.
Advocacy groups such as the Huntington’s Disease Youth Organization (HDYO) also have cautioned against the sham surgery.
In a March 6 e-mail, the organization stated that the “use of a sham neurosurgical procedure – requiring participants to undergo the risks of major surgery to the head including a lengthy time period under anesthesia without the possibility of therapeutic benefit – places an unnecessary burden on individuals already facing a progressive and fatal condition.” HDYO urged the use of “alternative trial designs … while minimizing avoidable risk to participants.”
Seeking to restore regulatory clarity
According to a report by Reuters, on April 1 the Rare Disease Advocacy, Biotechnology, and Investor Coalition sent a letter to President Trump, U.S. Health Secretary Robert F. Kennedy Jr., Medicare head Mehmet Oz, M.D., and FDA Commissioner Marty Makary, M.D.
The letter urged the leaders to restore regulatory clarity at the FDA as it considers a new leader for the agency’s Center for Biologics Evaluation and Research.
Headed by Vinay Prasad, M.D., who has resigned for the second time, the Center evaluates gene therapies such as AMT-130. Dr. Prasad’s departure follows a series of controversies involving the review of vaccines, gene therapies, and biotech drugs, including reversals of FDA promises. Biopharma executives, investors, members of Congress and others have criticized his actions.
The coalition includes nearly 100 patient disease advocacy groups, biotech executives, and investors. The letter noted that the Center had become less flexible in overseeing rare disease clinical trials.
The group has observed a drop in rare disease investment because of the uncertainties caused by the FDA.
“We believe it is of the utmost importance that the FDA chooses [for the Center] a leader who understands the unique challenges of rare disease development and respects and values the views of patients and physicians,” their letter stated.
A chance for the FDA ‘to reset’
An April 1 report by the news site BioPharmDive echoed the advocates’ critical analysis of the FDA.
The report observed that, after a “turbulent year” at the FDA caused by “constant leadership changes” and “erratic decision making,” the agency is as “unpredictable as it’s ever been.”
BioPharmDive concluded that Dr. Prasad’s departure by the end of April “could give the FDA a chance to reset.” Commissioner Makary promised to name a replacement before he leaves.
‘We can’t afford delays for rare diseases’
On February 26, Florida Sen. Rick Scott, another Republican, chaired a hearing of the Senate Special Committee on Aging, which addressed the FDA’s difficulties.
At the hearing, physicians, biotech leaders and rare disease patient advocates criticized the FDA for stifling innovation.
The hearing discussed FDA reversals of previous agreements that it had made with drug makers. One advocate pointed out that, from 2024 to 2025, the FDA had 65 percent fewer advisory committee meetings for new drugs and biologics (a medicine derived from a living organism as opposed to a chemical), including for rare diseases.
At the hearing, New York Sen. Kirsten Gillibrand, a Democrat, pointed out that about one in ten Americans have a rare disease. She stated that the FDA is “not working how it should be” as laid out by Congress.
“This is heartbreaking for patients, and it’s why we can’t afford delays and disruptions in treatment,” Gillibrand observed. “Rare diseases can progress rapidly, cause irreversible harm and, in some cases, premature death.”
