As FDA faces demands for greater clarity, uniQure presses ahead in search for Huntington’s disease gene therapy approval

  

As the reportedly dysfunctional U.S. Food and Drug Administration (FDA) faces demands for greater clarity in the wake of rare-disease drug denials, uniQure continues to seek a path to get AMT-130, its historically efficacious Huntington’s disease gene therapy, approved.

 

On March 2, after having surprisingly reneged last year on its promise to allow uniQure to apply for AMT-130 approval in 2026, the FDA “strongly recommended” that the firm conduct a new, full Phase III clinical trial.

 

In March, Wisconsin Sen. Ron Johnson, a Republican, launched an investigation of the FDA’s rejections of rare disease drugs. He 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.”

 

In an April 1 letter, the Rare Disease Advocacy, Biotechnology, and Investor Coalition urged President Trump and top administration health officials to restore regulatory clarity at the FDA.

 

A new way to win approval?

 

A possible avenue to AMT-130 approval opened on April 14. Teresa Buracchio, M.D., head of the FDA’s Office of Neuroscience, said at the National Organization for Rare Disorders (NORD) symposium in Arlington, VA, that the agency’s “plausible mechanism framework” for approval of bespoke gene therapies might be applied “to approve other therapies.” The news site Fierce Biotech reported on the symposium.

 

A bespoke therapy is given to a single individual, such as “Baby KJ,” the world’s first individual to be treated with a personalized (customized) CRISPR gene editing therapy, in 2025. KJ was born with a rare metabolic disease, severe carbamoyl phosphate synthetase 1 (CPS1) deficiency. The child is now thriving.

 

After FDA leaders raised the topic of individualized therapies in a November 2025 The New England Journal of Medicine article, the FDA in February issued a draft guidance for a new path to such treatments, calling it the “plausible mechanism framework.”

 

Dr. Buracchio observed that the framework is not specifically an approval pathway but a set of regulatory principles being applied to customized therapies for the first time, Fierce Biotech reported.

 

The special challenges of HD science

 

The Fierce Biotech article noted that Dr. Buracchio’s comments “offered some clarity to a confused rare disease sector rattled by high-profile regulatory drama.” That drama has resulted in part from uniQure’s use of patient registry data (also known as a natural history study) to analyze AMT-130, which was rejected by the FDA “even as such methods are part of the criteria that could enable approvals for tailored gene-editing therapies under the plausible mechanism framework.”

 

In March, the FDA had pointed out that AMT-130 is not an individualized therapy.

 

However, Dr. Buracchio said that the plausible mechanism framework “shouldn’t be a disadvantage” to non-individualized therapies.

 

Dr. Buracchio stated that the FDA is open to applying the plausible mechanism framework “conceptually” to Huntington’s disease broadly, or other diseases of comparably-sized populations.

 

A therapy needs to show “substantial evidence of effectiveness and a substantial improvement that’s clear and distinct from the natural history of the disease,” she said, noting that KJ demonstrated marked improvement in symptoms and reached developmental milestones.

 

By comparison, a slowly progressive neurodegenerative disease like HD “is going to be a harder case to make,” Dr. Buracchio said. “That’s because slowing the rate of decline is much harder. So, to me, this is less of a number issue and more of a nature of the disease issue.”

 

Presenting AMT-130 to the rare disease symposium

 

At the NORD symposium, David Margolin, M.D., Ph.D., uniQure’s vice president for clinical development, gave a presentation on AMT-130, addressing the FDA’s concerns.

 

As reported by Fierce Biotech, in response to the FDA’s requirement that the company run a Phase III trial and Dr. Buracchio’s point about the slowness of HD, Dr. Margolin stated that this slow progression makes it nearly impossible to show clear efficacy over a short period. This creates an “ethical challenge” when giving some patients a placebo or having them undergo the sham surgery.

 

As presented by Dr. Margolin at numerous conferences, including the key 21st Annual HD Therapeutics Conference in February, AMT-130 demonstrated a 75 percent slowing of HD progression over three years. (The conference is sponsored by CHDI Foundation, Inc., the largest private funder of HD research.) This was the first time that a drug has delayed HD.

 

Dr. David Margolin at the 2026 HD Therapeutics Conference (photo by Gene Veritas, aka Kenneth P. Serbin)

 

Enroll-HD in place of a placebo

 

A second Fierce Biotech article on the NORD symposium focused on how academics and biopharma leaders are breaking the mold of traditional clinical trials with creative methodologies, aiming to garner interest and support from peers and regulators.

 

A common approach in rare disease drug development is the use of an external control or comparator, which replaces the placebo in a classic clinical trial. As noted, instead of a sham trial, uniQure took this approach by using data from the HD patient registry, called Enroll-HD.

 

With more than 22,000 participants, Enroll-HD is “one of the most remarkable prospective registry trials that's ever been run,” according to CHDI Chief Scientific Officer Robert Pacifici, Ph.D.

 

Tracy Beth Høeg, M.D., Ph.D., the acting director of the FDA’s Center for Drug Evaluation and Research, stated at the NORD event that the agency is finalizing guidance on external controls. This, she added, will hopefully “give clarity to sponsors about what sort of evidence we would be looking for and willing to accept for approval of rare disease drugs.”

 

As reported by Fierce Biotech, Dr. Margolin spent much of his NORD talk on uniQure’s use of a statistical technique known as “propensity score matching.” As he explained at the Therapeutics Conference, this involves finding in Enroll-HD individuals similar to those in the uniQure trial and including them as controls. At the NORD meeting, he pointed out that the difference between AMT-130 clinical trial participants and the individuals uniQure selected from Enroll-HD was negligible.

 

Dr. Margolin also responded to the FDA’s criticism that one of the clinical trial measurements uniQure used for AMT-130 was too subjective, leaving the participants susceptible to a placebo effect that could not be detected when using Enroll-HD.

 

An ongoing dialogue with the FDA

 

“I know there’s active dialogue with FDA and the Huntington’s disease organizations regarding how to interpret and best utilize these clinical scored measures, and that’s an ongoing process,” Dr. Margolin stated.

 

Meanwhile, the HD community and its allies continue to pressure Congress and public officials to focus on HD and bring AMT-130 a fair hearing at the FDA.

 

Or, in the current political and business climate, perhaps the HD community also needs a vast stroke of good luck, celebrity connections, and publicity, as biotech observers have noted with dark humor.

 

Joe Rogan to the rescue?

 

On April 18, Pearl Freier, president of Cambridge Biopartners, Inc., asked on the social media platform X how the HD community could overcome an FDA rejection based on the “personal negative opinion” of FDA Commissioner Marty Makary and/or U.S. Secretary of Health and Human Services Secretary Robert F. Kennedy Jr.

 

She added: can the HD community make a deal with growth stage venture capital firm and prediction market company “Kalshi and/or Polymarket?”

 

Adam Feuerstein, the senior writer covering biotech at the essential STAT, responded to Freier’s post: “I guess people living and dying with Huntington’s disease need an influencer/podcaster to text Trump. That’s how the FDA works these days.”

 

Feuerstein linked to an X post detailing how popular podcaster Joe Rogan revealed how the president “IMMEDIATELY offered FDA approval for a psychedelic treatment in a text chain Because the data was SO CONVINCING and STUNNING.” The treatment is for depression and other conditions.

 

Finding comfort in Pope Francis’ embrace of the HD community

 

These are trying times for the world, with the U.S. again in a major war and world peace once again at risk. For the HD community, it is distressing that AMT-130 is rejected after seven years of clinical study by uniQure.

 

For comfort I remember highlights of the HD cause such as Pope Francis’ 2017 audience with HD families, declaring that the disease should be “hidden no more” and HD families respected and loved. I also look with hope to the first American head of the Church, Pope Leo XIV, who has continued Francis’ emphasis on mercy.

FDA recommends a full clinical trial for uniQure Huntington’s disease drug, further delaying potential approval

  

Delaying but not blocking AMT-130, uniQure’s emerging gene therapy to slow Huntington’s disease progression, the U.S. Food and Drug Administration (FDA) “strongly recommended” that the company conduct a full-blown, Phase III clinical trial, rather than assess an application for drug approval based on an earlier trial that showed historic efficacy.

 

The news came in a March 2 uniQure press release, relying on official minutes from the company’s January 30 high-priority meeting with the FDA about the AMT-130 program. The drug has been shown to slow the progression of by HD symptoms by as much as 75 percent.

 

As discussed below, this action reflects the more conservative trend of at least parts of the FDA under the Trump administration.

 

Based on the meeting minutes, the FDA has maintained its new decision that data from the earlier AMT-130 Phase I/II trial, using the global Enroll-HD patient database as a comparison, cannot be used as primary evidence for a drug application, the release stated.

 

The company added: “The FDA strongly recommended uniQure conduct a prospective, randomized, double-blind, sham surgery-controlled study. uniQure intends to continue engaging with the FDA regarding Phase III development considerations and plans to request a […] meeting in the second quarter of 2026 to further discuss potential study design approaches.”

 

A prospective, randomized, double-blind study is a standard clinical trial in which neither patients nor researchers know who receives the drug. A sham (pretend) surgery, which uniQure did on a few clinical trial participants early in the Phase I/II study, will now be required as a placebo, which is standard in most clinical trials. Relying on Enroll-HD data had taken the place of the sham surgery, which uniQure had stopped doing for ethical reasons. Injecting AMT-130 into the brain involves a twelve-plus-hour brain operation.

 

uniQure’s plans

 

“While we did not reach alignment on a submission pathway based on the Phase I/II data, we believe the totality and durability of our data warrant continued substantive dialogue” with the FDA regarding “regulatory flexibility,” uniQure CEO Matt Kapusta stated. “We remain committed to engaging with the FDA to determine a clear, scientifically grounded, and efficient path forward for AMT-130. We are deeply grateful for the resilience and support of the Huntington’s disease community and remain committed to standing with patients and their families.”

 

“Regulatory flexibility” refers to FDA programs that, for example, allow potential accelerated drug approval. uniQure had previously pursued that.

 

Based on its studies so far, which include three years of analysis, uniQure plans to share a four-year analysis, “which we expect to complete in the third quarter of 2026,” Daniel Leonard, the company’s director of global patient advocacy, wrote in a letter e-mailed to the HD community. “We believe the extended follow-up will provide additional insight into both the durability and the magnitude of the effects of AMT-130.”

 

Removing bias from the study

 

Last September, uniQure had reported that AMT-130 demonstrated a 75 percent slowing in the progression of HD over a three-year period. However, in crisis under the Trump administration, the FDA backtracked on its word regarding the firm’s plans to submit its application in early 2026, prompting 48,000-plus people to sign two petitions to the agency asking to keep its promise.

 

On February 24, a top uniQure scientist presented an updated analysis of AMT-130 at the 21st Annual HD Therapeutics Conference.

 

David Margolin, M.D., Ph.D., uniQure’s vice president for clinical development, gave the first scientific presentation at the Therapeutics Conference. He addressed the question, raised by the FDA, regarding the use of data from Enroll-HD, instead of a placebo, in the AMT-130 clinical trial.

 

“We relied on an external comparator cohort, which is selected from participants in the Enroll- HD Natural History Study, which has advantageous characteristics as a comparator,” Dr. Margolin explained. However, whereas the AMT-130 clinical trial takes MRI measurements of the brain, including the crucial striatum, Enroll-HD participants do not.

 

To mitigate the “potential bias” from this difference, uniQure used a statistical technique known as “propensity score matching,” Dr. Margolin stated. As he explained, this involves finding in Enroll-HD individuals similar to those in the uniQure trial and including them as controls.

 

The volume of the striatum (which demonstrates the loss of brain tissue in HD) as a factor in the AMT-130 trial “becomes moot,” Dr. Margolin continued. Other patient characteristics from Enroll-HD “can fully substitute” for that measure, such as neuropsychological testing and measurements of a person’s involuntary movements, he said.

 

“This analysis supports the validity of the three-year efficacy results,” Dr. Margolin concluded. uniQure will publish results of the AMT-130 trial in a scientific journal.

 

Dr. David Margolin (above) displaying a slide demonsrating AMT-130's efficacy in slowing HD progression and (below) enjoying down time at the Therapeutics Conference (photos by Gene Veritas, aka Kenneth P. Serbin)

 

 

‘At the precipice’ of effective treatments

 

Held at the Parker hotel in Palm Springs, CA, the HD Therapeutics Conference concluded on February 26. It is sponsored by CHDI Foundation, Inc., the largest private backer of the quest for HD therapies.

 

Like potential remedies in other HD programs, such as Roche’s tominersen, AMT-130 lowers (reduces) the amount of defective huntingtin protein.

 

“We have multiple shots on goal in the huntington-lowering arena, things like uniQure,” CHDI Chief Scientific Officer Robert Pacifici, Ph.D., told me in an interview on February 27. “While it's true that none of them have made it out the other end with a positive ruling in a pivotal Phase III trial, we're at the precipice of the types of signals that will indicate that there is a clinically meaningful benefit by lowering huntingtin.”

 

Such benefit must be confirmed through a Phase III trial or conditional approval by the FDA.

 

This “exciting” development encourages other companies to invest in late-state trials, Dr. Pacifici added, noting that lowering huntingtin hits at the root causes of HD.

 

 

Dr. Pacifici at the conclusion of the Therapeutics Conference (photo by Gene Veritas)

 

A ‘more conservative’ FDA

 

Cristina Sampaio, M.D., Ph.D., CHDI’s chief medical officer, joined the foundation in 2011 after serving on two entities in the European Medicines Agency (EMA), the FDA’s counterpart in Europe.

 

In a February 25 interview, Dr. Sampaio, who advises companies on their clinical trial programs, observed that companies other than uniQure have faced changes in course with the FDA.

 

Under the Trump administration, she said, the FDA become “more conservative,” especially in the Center for Biologics Evaluation and Research, the unit in charge of evaluating drugs such as AMT-130. News reports have also noted the conservative trend.

 

FDA ‘ping pong’ not healthy

 

At the same time, Dr. Sampaio stated that changes in the FDA’s approval process are “problematic” for uniQure and other firms.

 

“Companies rely on what they discuss with FDA,” Dr. Sampaio said. “This for them is vital. It's how they define their projects, it's how they define how long it will take to the market, it's how they define their budget, how much it will cost.”

 

Changing positions from one day to the next “creates a lot of uncertainty to the market,” she observed. “This ping pong of FDA is not healthy.”

 

As news organizations have reported, changes in leadership at the FDA, firings, and the exit of mid- and high-level managers have created “uncertainty” and “turmoil” at the agency, Dr. Sampaio said.

 

More susceptible to politics

 

Whereas decisions about drugs in Europe tend to be more “democratic,” the FDA is “hierarchical,” making it more susceptible to politics, Dr. Sampaio observed.

 

Even so, she added, outside of normal lobbying, “there was no evidence” until now that political influence was affecting the FDA.

 

“But until these big changes with the Trump administration, the FDA was very respected as an independent body,” Dr. Sampaio asserted.

 

External comparisons are good science

 

Dr. Sampaio noted that the uniQure AMT-130 clinical trial program began in 2019 as an exploratory venture, mainly to test for safety. As time passed and the personnel at the firm changed, the goals for AMT-130 became “more ambitious.”

 

“But this was not pre-planned,” she said. “And this is a weakness. That said, I believe they have been as careful as they can be, given the circumstances, and given the data they have.” The 17 patients about which data have been revealed is also a “small” number, she acknowledged.

 

The decision to use Enroll-HD as a comparison was also first “pushed by the FDA,” Dr. Sampaio noted, albeit under the previous administration.

 

Use of Enroll-HD as an “external comparator” is good science, Dr. Sampaio emphasized, noting that in oncology a similar technique has been used for more than a decade.

 

AMT-130 data moving in the right direction

 

Significantly, all of the AMT-130 data go “in the same direction,” showing improvement in the symptoms, she said. “This is very powerful.”

 

If AMT-130 were granted accelerated approval, it would be conditional, with the drug having to be removed from the market if problems emerged, Dr. Sampaio explained. Accelerated approval would also require ongoing study of the drug for safety and efficacy.

 

Dr. Margolin’s presentation at the therapeutics conference resolved scientific doubt regarding the volume of the striatum, Dr. Sampaio said. “This alleviated the concern that the population in this trial was not representative.”

 

Dr. Sampaio (right) with Dr. Hoa Huu Phuc Nguyen of Ruhr University Bochum, Germany (photo by Gene Veritas)

 

Some think AMT-130 needs more work

 

Blair Leavitt, M.D., a veteran HD researcher and professor of medicine at the University of British Columbia, also weighed in on AMT-130 and the FDA. Dr. Leavitt is the co-founder and co-editor-in-chief of the Journal of Huntington’s Disease.

 

Dr. Leavitt’s lab received funding from uniQure to conduct research.

 

“We tested in our mouse model of Huntington's disease and showed benefits of the uniQure approach in that mouse model,” he explained in a February 26 interview at the Therapeutics Conference. He thinks that the uniQure clinical trial was “designed primarily to show the safety and tolerability of the approach and the agent in individuals with Huntington's disease, and it absolutely did that.”

 

The AMT-130 program has opened “a whole field of gene therapy and gene editing approaches, which is incredibly exciting for our field,” Dr. Leavitt added.

 

However, Dr. Leavitt thinks more work needs to be done on AMT-130. “I would disagree with some people who have suggested [that the work done so far] is sufficient to prove efficacy,” he said, adding that “a proper controlled trial” is ultimately needed. In effect, this was what the FDA has now recommended to uniQure.

 

Regarding the 75 percent slowing of symptoms with AMT-130, Dr. Leavitt observed that “we're talking about a decline in all of the patients, on average, but a less decline. That certainly is positive. That might be the best we can hope for with many of our therapies, but ultimately, it's not a complete reversal of symptoms.”

 

Uncertainty at FDA ‘bad for all’

 

Dr. Leavitt, as a Canadian citizen, declined to comment on the political impact of the Trump administration on the FDA.

 

“But I do believe it is a difficult time for drug development,” he said. “The FDA is really the premier regulator for most of the world, and uncertainty at the FDA leads to uncertainty in drug development, and that's bad for all of us.”

 

Such uncertainty “is the last thing we need at this point, because we are on the precipice of a number of therapies, and I'm sure we're going to have efficacy.”

 

Others firms’ interactions with the FDA

 

Veteran HD researcher Jang-Ho Cha, M.D., Ph.D., the chief science and medical officer of Latus Bio, addressed a question from the audience after his February 24 presentation about the company’s HD program.

 

Ed Wild, M.D., Ph.D.,wanted to know whether Latus had a strategy for engaging with the FDA and its Center for Biologics Evaluation and Research to obtain drug approval. Dr. Wild also asked whether an industry consortium could help “to at least extract some firm guidance?”

 

“Yes, we have a strategy to engage with them,” Dr. Cha responded. Latus hopes to soon submit an Investigational New Drug (IND) application.

 

“At this point, we will wait until we have our IND package to show them everything we’ve got,” Dr. Cha continued. “I’m not sure exactly, if we asked a question from the FDA, we would get an answer that we could rely on exactly at this point. We are watching with a lot of interest other companies who are having interactions with the FDA, because it’s relevant to all of us.”

 

Will the truth conquer all?

 

Dr. Pacifici offered a concluding reflection regarding the FDA.

 

“In terms of the interaction between the companies and the regulators, I guess I'm a bit of an optimist in this regard,” Dr. Pacifici told me. “I truly believe that politics and money and all of the other perverse things that surround us, notwithstanding, that at the end of the day, the truth conquers all.”

 

“I think that these are scientific people,” he said. “I think that they're going to look at the body of data and evidence, and eventually I think they're going to make the very best decision to get things out as quickly and as safely as possible to the patients who so desperately need these treatments.”

 

For additional coverage, visit HDBuzz.

 

Next time: Dr. Pacifici’s overview of the conference and his video interview with me.

uniQure’s AMT-130 at the forefront of 21st Huntington’s Disease Therapeutics Conference

  

AMT-130, the uniQure gene therapy that successfully slowed the progression of Huntington’s disease before being obstructed from approval by the U.S. Food and Drug Administration (FDA), stands at the forefront of the leading HD research conference that starts today, February 23, in Palm Springs, CA.

 

The 21st Annual Huntington’s Disease Therapeutics Conference, which I have described as the Super Bowl of HD research, takes place at the Parker hotel. It is sponsored by CHDI Foundation, Inc., the largest private funder of HD research.

 

“In recent years HD drug discovery has become increasingly anchored in strong human genetic and clinical evidence, allowing us to focus on mechanisms most likely to yield disease-modifying benefit,” wrote Robert Pacifici, Ph.D., the CHDI chief scientific officer, in his welcome letter to the conference attendees. “Few developments capture this momentum more clearly than the recent topline results announced by uniQure from the pivotal Phase I/II study of AMT-130 suggesting that lowering [decreasing] mutant huntingtin in people confers a real clinical benefit, an important proof of biological principle.”

 

Dr. Pacific did not refer to the FDA roadblock but asserted that the AMT-130 “findings represent an encouraging milestone for the HD community.”

 

For its clinical trial analysis uniQure has relied on the CHDI-backed Enroll-HD, the global registry of HD-affected individuals and their families. uniQure has presented its data at the therapeutics conferences.

 

Dr. Robert Pacifici, wearing a Team Hope shirt from the Huntington's Disease Society of America, overseeing the 2025 Therapeutics Conference (photo by Gene Veritas, aka Kenneth P. Serbin)

 

AMT-130 talk in the lead-off

 

Dr. Pacifici and the conference planners scheduled a report on AMT-130 as the first presentation at the start of the opening science session on February 24.

 

David Margolin, M.D., Ph.D., uniQure’s vice president for clinical development, will give a talk titled “AMT-130 slows Huntington's disease progression at 3 years: Propensity score weighting mitigates potential bias from striatal volume absence in Enroll-HD.”

 

Because AMT-130 has been administered via a spinal injection that involves 12-plus hours of surgery, uniQure had no placebo group – those not getting an operation –but instead chose to use data from Enroll-HD as a comparison group.

 

After extensive consultations with the FDA in 2024, uniQure had gotten permission from the agency to use the Enroll-HD data. In November 2025, the FDA told uniQure that Enroll-HD data might no longer be “adequate.”

 

The HD community mobilized immediately, garnering 48,000-plus signatures on two petitions delivered to FDA headquarters on January 22.

 

The abstract of Dr. Margolin’s presentation does not reference the FDA but states that the Enroll-HD data about loss of striatal volume (shrinkage in the striatum, located deep in the brain and severely affected in HD) was helpful in the analysis of the clinical trial data. He reasserted the importance of MRI measurements of such brain loss.

 

Awaiting news about the FDA

 

uniQure announced on January 9 that it had scheduled a high-priority meeting with the FDA, which according to regulations had to occur within 30 days. The FDA must produce final minutes of the meeting.

 

As of this writing, uniQure has not reported on the results of the meeting.

 

At the conference, the several hundred scientists, biopharma reps, and advocates like me will anxiously await the latest news on AMT-130.

 

Stay tuned for my reports on the event.

Wonderful news: uniQure’s one-and-done drug slows Huntington’s disease

 

AMT-130, a one-time gene therapy developed by uniQure, has successfully slowed the progression of Huntington’s disease.

 

While that is not a cure, and the therapeutic process is hardly simple, it is the first evidence that scientific progress translates into meaningful results for those suffering from HD.

 

The treatment is far more complex than a pill: it involves 12 to 18 hours of delicate brain surgery. A neurosurgeon injects AMT-130 directly into the brain under the guidance of an MRI. As a gene therapy, AMT-130 requires just this one application. (Watch the uniQure video about how AMT-130 is administered here).

 

According to clinical trial results reported by uniQure on September 24, AMT-130 achieved its main goal (primary endpoint) and demonstrated a 75 percent slowing in the progression of the disease over a three-year period.

 

“High-dose AMT-130 also demonstrated statistically significant slowing of disease progression as measured by TFC, a key secondary endpoint, and favorable trends across additional clinical measures,” the release stated. TFC is total functional capacity. It refers to a person’s ability to function – a key loss in HD.

 

Other progress

 

The company, based in Lexington, MA, and Amsterdam, reported that AMT-130 also reduced the measure of a protein known as neurofilament light, a marker of disease that reveals stress on the brain.

 

The clinical trial showed “favorable trends” in other second measures of motor (movement) and cognitive function, the release stated. Movement disorders and cognitive loss are major HD symptoms. Trial results demonstrated that AMT-130 is safe and well-tolerated.

 

“I believe these groundbreaking data are the most convincing in the field to date and underscore potential disease-modifying effects in Huntington’s disease, where an urgent need persists,” Sarah Tabrizi, M.D., Ph.D., a leading HD specialist at University College London, stated in the release. “These data indicate that AMT-130 has the potential to meaningfully slow disease progression – offering long-awaited hope to individuals and families impacted by this devastating disease.”

 

 

David Margolin, M.D., Ph.D., uniQure's vice president for clinical development, presents data illustrating ATM-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).

 

Transforming the HD landscape

 

AMT-130 seeks to lower the amount of harmful mutant huntingtin protein in the brain cells of patients. Whether the drug has actually done this has yet to be verified.

 

In early 2026, uniQure plans to apply to the U.S. Food and Drug Administration (FDA) for drug approval. Pending drug approval, the drug would be launched in the U.S. later in 2026.

 

“We are incredibly excited about these topline results and what they may represent for individuals and families affected by Huntington’s disease,” stated Walid Abi-Saab, M.D., chief medical officer of uniQure. “These findings reinforce our conviction that AMT-130 has the potential to fundamentally transform the treatment landscape for Huntington’s disease, while also providing important evidence supporting one-time, precision-delivered gene therapies for the treatment of neurological disorders.”

 

Hopes for a life-long treatment

 

“This is the first time any drug has been shown to alter the course of HD in people in a clinical trial,” the scientist-written website HDBuzz stated. “uniQure believes that AMT-130 has the potential to be a treatment that lasts for life.”

 

uniQure officials told HDBuzz that, beyond the FDA, they plan to seek approval with other regulators, including the European Medicines Agency, which oversee drug approvals in Europe.

 

HDBuzz cautioned that key details need to be worked out before AMT-130 can be administered to a large group of people beyond the fewer than 30 people whose data were analyzed by uniQure.

 

Only some of those individuals received the high dose of the drug that proved effective. Also, because AMT-130 requires an operation, the company must find a way to provide access to the drug, and at an affordable level, to a larger number of people.

 

On the whole, despite the caveats and complexities, this is wonderful news for the HD community.

 

"We never in our wildest dreams would have expected a 75% slowing of clinical progression," Dr. Tabrizi told the BBC.