Latest data show uniQure gene therapy continues to slow Huntington’s disease, but at a reduced rate

  

The latest update from uniQure on its gene therapy for Huntington’s disease demonstrates that it continues to slow the progression of Huntington’s disease, but at a reduced rate compared to data from 2025.

 

Last year uniQure reported that its drug, AMT-130, had slowed HD progression by 75 percent over a three-year period.

 

Breaking its promise to allow uniQure to apply for drug approval in early 2026, the dysfunctional U.S. Food and Drug Administration (FDA) recommended that the company conduct a new, full-blown clinical trial of AMT-130. After the HD community petitioned the FDA and the agency’s ineffective commissioner resigned, uniQure was allowed to submit its application, based on data from people who had completed three years in the study. It did so on September 2.

 

On September 29, uniQure released new data from a group of twelve clinical trial volunteers who had completed four years in the study. (Click here for the press release.)

 

Those individuals showed a slowing of the disease by 44 percent – an encouraging sign but, as uniQure itself acknowledged, not considered statistically significant because that improvement could have occurred by chance.

 

Key measures have improved

 

AMT-130 now has an official generic name, ifezuntirgene inilparvovec.

 

"Four years after a single administration, ifezuntirgene inilparvovec continues to show meaningful slowing of disease progression, further strengthening our conviction in its benefit for people living with Huntington’s disease," Walid Abi-Saab, M.D., uniQure’s chief medical officer, stated in the release.

 

Dr. Abi-Saab reported that at 48 months, Total Functional Capacity (TFC), a primary measure of the drug’s effect, “demonstrated consistent slowing of functional decline.” The higher doses of the drug showed greater benefit, he noted.

 

The updated analysis of those on the drug through 36 months also demonstrated a “substantial effect” on TFC and cUHDRS, another key measure of HD, Dr. Abi-Saab stated. These data reinforce the data already included in the application to the FDA, he added.

 

 

Scientists’ views

 

HD scientists have said that even if the hoped-for 75-percent slowing of HD by ifezuntirgene inilparvovec is less, it could still have a big impact on the disease.

 

Commenting on ifezuntirgene inilparvovec at the Huntington’s Disease Foundation’s biennial conference in August, Sarah Tabrizi, M.D., Ph.D., one of the medical leaders of the uniQure trial, said that the actual effect of the drug could be in the range of 40-50 percent, still a “fantastic” improvement, unprecedented in HD research.

 

"What I find particularly notable in the expanded data is the consistently meaningful treatment effect at 36 months, and the apparent stability of the functional capacity benefit through Month 48,” Victor Sung, M.D., professor of neurology at the University of Alabama at Birmingham (UAB), director of the UAB Huntington’s Disease Clinic, stated in the uniQure release. “Total Functional Capacity tracks things that matter the most to patients and families – ability to work, perform household chores and handle daily self-care activities.”

 

Seeing that treatment effect “maintained at four years is meaningful for people living with this relentlessly progressive degenerative disease," Dr. Sung added.

 

“A 44 percent slowing of disease progression, now out to 48 months, is still unprecedented and of meaningful value to this patient population,” said uniQure CEO Matt Kapusta. “It’s something no other program in Huntington’s disease has been able to achieve.”

 

Hopeful, but complex results

 

The scientist-written website HDBuzz noted the “hopeful, but complex results” in the uniQure update, including the company’s reliance on external comparators rather than a placebo. This results from the rareity of HD and the fact that ifezuntirgene inilparvovec is injected into the brain with a surgery lasting 12-18 hours.

 

“With only a small number of people followed for 4 years, there is uncertainty around this estimate, so the 44% figure should be interpreted cautiously,” HDBuzz wrote.

 

Jeff Carroll, Ph.D., a leading HD scientist at the Allen Institute and like me an HD gene carrier, reviewed the new uniQure data for STAT. Dr. Carroll was not surprised to see the treatment effect of the drug narrow, because the drug was administered to only twelve individuals.

 

“The fact that we continue to see any benefit in cUHDRS functional capacity scores is hugely exciting,” Dr. Carroll said.

 

“I’m not surprised by the four-year results because this isn’t a cure,” commented Help4HD International advocate and HD gene carrier Lauren Holder. “This is a slowing-of-disease-progression treatment, and so I would expect there’s still decline going on, and we’re going to see that on testing, and that doesn’t mean it’s not working.”

 

Advocates meet with FDA at HD roundtable

 

Before these latest actions by uniQure, and in the wake of the crises created by the former commissioner, the FDA invited representatives of six HD organizations to a meeting at its headquarters.

 

The hour-long lunchtime roundtable meeting on July 30 was chaired by Acting Commissioner Kyle Diamantis, along with several staff members.

 

So far, no HD leader has granted me an interview about this meeting. On July 31, they posted a note on Instagram thanking Diamantis for the roundtable.

 

“We appreciate the opportunity to bring together people with lived experience, advocates, researchers and clinicians to engage in meaningful dialogue,” the note stated. “Collaboration like this ensures the voices of the Huntington’s disease community remain at the center of research, drug development, and regulatory decision-making.”

 

The organizations were Help4HD, HDReach, Huntington’s Disease Foundation, Huntington Study Group, Huntington’s Disease Society of America, and Huntington’s Disease Youth Organization.

 

Regarding the FDA, the uniQure data update, and the company’s pending drug application, Help4HD International’s Holder said, “I honestly can’t say one way or the other when it comes to the FDA. We need to make sure we are educating people at the FDA because I don’t want them misunderstanding the numbers [data] and causing an issue.”

 

Holder added that she remains “very hopeful about this treatment and still very impressed with the results.”

Citing lack of efficacy, Roche halts two Huntington’s disease drug programs, while other initiatives forge ahead

  

In deeply disappointing news for the Huntington’s disease community and beyond, Roche announced on July 9 that it stopped two drug development programs because of lack of efficacy in slowing the progression of the disease.

 

Tominersen, a gene silencing drug developed by Ionis Pharmaceuticals, Inc., envisioned as a “laser-guided missile” against HD, in 2021 demonstrated lack of efficacy in a first worldwide trial run by Roche.

 

Roche, however, had believed that tominersen might show at least some efficacy in people at earlier stages of Huntington’s. So it launched a less ambitious second trial in January 2023.

 

In a statement to the HD community, after completing the 16-month treatment period of all trial participants and analyzing the data, Roche stated that “there was no meaningful impact on clinical efficacy for the study participants receiving tominersen, compared to those on placebo.”

 

Roche also said it had halted a preliminary Phase I clinical trial of the HD gene silencing drug RG6496, which had enrolled just three volunteers so far, “because we can no longer offer participants the possibility of long-term treatment” based on data from new animal studies.

 

“We have been humbled and inspired by the 1,500+ HD families and broader community who contributed to both programs – tominersen since clinical studies began in 2015 with our partner Ionis Pharmaceuticals, and RG6496 more recently,” the Roche statement noted. “These contributions changed the history of HD drug development – proving the protein that causes HD could be lowered in humans, shaping new research and approaches, which will undoubtedly lead to future breakthroughs.”

 

 

The setback ‘stings’

 

HD family members expressed sadness about the announcement from Roche.

 

In a Facebook posting, Help4HD International advocate Lauren Holder, like me an HD gene carrier, said the news was “disappointing.”

 

“This was the clinical trial I was participating in,” Jessica Robbins, who has HD, wrote on Facebook, granting me permission to quote her. “Unfortunately, it has come to an end.”

 

Jessica had dedicated two years to the tominersen trial.

 

“I’m not going to lie – am incredibly disappointed and heartbroken,” she wrote. “A setback like this stings, but I don’t regret a single day of it. Even though this door closed, the data from our trial will still help research in the long run. I am proud to have played a part in this fight against HD.”

 

I, too, had hoped to take tominersen, having tracked its development since 2008.

 

Scores of other initiatives

 

Drug development does take years, even decades, as tominersen’s story illustrates.

 

I had found the second trial of tominersen far less compelling, though necessary for the field to advance, because the drug would have been able to help only a portion of HD patients. So the disappointment for me does not match what I felt with the community in 2021.

 

I do remain optimistic that effective therapies will be found – if not for me, at least for those in the next generation, like my nephew Greg Noble, also an HD gene carrier.

 

The HD community has especially focused on uniQure’s AMT-130, a gene therapy that, for the first time, slowed the progression of HD. uniQure and the community have worked tirelessly to overcome the regulatory roadblocks placed by the Trump administration.

 

Roche, too, has not given up on HD science and is working on its own gene therapy.

 

PTC Therapeutics and Novartis have partnered on a clinical trial program using a huntingtin splicer modulator. Skyhawk Theapeutics’ HD program has also shown promise, and the controversial pridopidine, under study by Prilenia, will undergo a new Phase III trial to determine whether the drug can slow progression.

 

Scores of companies continue to work on HD, as do academic labs around the world.

 

I do feel hope!

 

(Disclosure: I hold a symbolic amount of Ionis shares.)

‘Let’s Talk About Huntington’s Disease’: 2019 HD Awareness Month kicks off

May is Huntington’s Disease Awareness Month. As in past years, the Huntington’s Disease Society of America (HDSA) is encouraging HD families to share their experiences in a social media campaign, #LetsTalkAboutHD.

Other HD advocacy groups are also marking HD Awareness Month.

As a presymptomatic HD gene carrier who lost his mother to HD in 2006, I kicked off my own participation as a guest May 1 on Help 4 HD International’s podcast Help 4 HD Radio (click here to hear the program.)

I recalled my family’s struggle with HD in an interview with podcast host and HD gene carrier Lauren Holder, the Help 4 HD Radio producer and the 2014 HDSA Person of the Year.

“We need to continue telling our stories,” I said in response to Lauren’s question about how to promote HD Awareness Month, emphasizing the need to attract those unaffected by HD to our cause.

I also highlighted the “real hope” for the first effective HD treatments with clinical trials such as the Ionis-Roche project. These trials are “really unprecedented in the history of HD,” I noted. In the mid-1990s, when my mother was diagnosed, there had been “zero hope,” I recalled.

The next day, I posted HD Awareness Month flyers on my office door at the University of San Diego.

I’m ready for #LetsTalkAboutHD!

Gene Veritas, aka Kenneth P. Serbin, at his office at the University of San Diego (photo by Yi Sun, Ph.D.)

A painful silence

My conversation with Lauren stirred up painful memories – but also provided fresh insight – about my own path from refusing to talk publicly about HD to exiting the “terrible and lonely HD closet” in 2012 with an essay, “Racing Against the Genetic Clock,” in The Chronicle of Higher Education.

Regarding my “coming out” about HD, Lauren wanted to know: “How did it make you feel? Was the process hard? Did you feel a sense of relief?”

“Deep down, I knew that someday I would need to go public, in some way or another, because it’s very hard to be an advocate without telling people about your story,” I said.

I recounted one poignant dilemma – discussed in public for the first time in the podcast – in the early 2000s. Back then, HDSA-San Diego was joining other chapters around the country in hosting the organization’s first fundraising galas.

“I would volunteer for the galas,” I told Lauren. “I was writing the newsletter that we would distribute at the galas. But I would never tell anybody my story.”

I was known in other San Diego circles for my work as a scholar of Brazil, and once I had given a local public talk on that country.

“I had met this one couple [at my Brazil talk],” I explained to Lauren. “And then, a year or two later, they showed up at one of our galas. So it was like, ‘Wow!’ They were wanting to know what I was doing at this gala here. And I said, ‘Well, this is my personal commitment to charity and making a difference.’

“And I didn’t tell them my story,” I explained. “It’s that kind of situation that was very difficult for me, because I was afraid of being outed, because nobody at my work knew my status. I was worried about losing my job and losing my insurance, and, if I were ever to switch jobs, could I get health insurance again? All of the concerns that people in our community, and other communities, have.

“I really just felt bad that I couldn’t – and wouldn’t at that point – share my story.”

Becoming an open, honest advocate

Going public “allowed me to be a much, much better advocate, an honest advocate,” I told Lauren. “I can talk openly about HD and my family situation.”

My essay “Racing Against the Genetic Clock” shocked my colleagues at work and around the country, I recalled.

However, I believed that the article was necessary because I “wanted to take away the fear of talking about Huntington’s disease” for others.

“To this point, I have not, to my knowledge, suffered any discrimination,” I added “And, of course, I’m still asymptomatic. Who knows what will happen if and when I become symptomatic? Things could change.”

However, until now, “I’ve been treated with respect,” I said. Living outside the “HD closet” has “been a very positive experience.”

The prohibition of insurance discrimination for people with pre-existing conditions in the Affordable Care Act and the passage of the Genetic Information Nondiscrimination Act have further encouraged me, I added.

#LetsTalkAboutHD!

Going public about one’s HD story is a “personal decision,” I observed.

Those unready to tell their stories openly can still participate in #LetsTalkAboutHD by starting with relatives and close friends, I said.

In the HD community, we all have important stories.

As I’ve told Lauren and so many others, “Together we will defeat HD!”

Sadly, HD and juvenile HD patients continue to die. HD Awareness Month provides our community with the opportunity to renew our energies and tell the world of the urgent need for treatments.