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.”

Huntington’s disease community urges FDA to get on the right side of history for uniQure gene therapy

 

Even as uniQure, in a December 4 press release, has reconfirmed – based on meeting minutes – the decision by the U.S. Food and Drug Administration (FDA) to roll back its permission to apply for a Huntington’s gene therapy drug approval, more than 43,000 people have signed two petitions demanding the agency to uphold its original plan.

 

As recounted here, uniQure and others in the frustrated biotech sector believe that the FDA has become dysfunctional under the Trump administration.

 

In September, uniQure announced that its drug, AMT-130, had slowed the progression of HD by 75 percent over three years – a historic first.

 

Then, on November 3, uniQure announced that, after its October 29 meeting with the FDA, the agency had abruptly switched gears regarding AMT-130.

 

On December 8, the life sciences hub BioSpace reported that “rare disease leaders” want “regulatory consistency” after a “chaotic year” at the FDA.

 

Overcoming the ‘whiplash of the FDA’s about-face’

 

The key biotech site STAT has continued to report on the crises in leadership and turmoil at the FDA.

 

As of December 9, two online petitions to the FDA from HD advocates have garnered more than 43,000 signatures.

 

Click here and here for the petitions.

 

In the words of the scientist-written site HDBuzz, “The HD community has not remained silent through the whiplash of the FDA’s about-face from just five months prior, when they stated that data from the ongoing trials would be sufficient to support accelerated approval.”

 

Honors for AMT-130 researcher

 

“We are committed to collaborating with the FDA to advance AMT-130 to patients and their families as rapidly as possible,” CEO Matt Kapusta stated in the company’s December 4 release. “The support we have seen these last weeks from the Huntington’s disease community, including patients, families, caregivers, clinicians and advocates, reinforces the urgency of the unmet need in Huntington’s disease.”

 

Further validation of uniQure and the AMT-130 clinical trial came on December 8, when the key journal Nature announced that Sarah Tabrizi, M.D., Ph.D., a leading HD specialist at University College London and one of the medical leaders of the AMT-130 clinical trial, is “part of Nature’s 10, a list of people who shaped science in 2025.”

 

Titled “Sarah Tabrizi, Huntington’s hero,” the article about her describes her decades-long efforts to treat HD.

 

“I want to see if we can prevent Huntington’s from ever occurring,” Dr. Tabrizi told Nature.

 

As we approach the holiday season and the hopes that HD advocates will persuade the FDA to resume its support of the agreed-to plan for AMT-130, the recognition of Dr. Tabrizi and the community’s massive efforts signal that the FDA should be on the right side of history in this urgent fight to end devastating diseases.

 

Dr. Sarah Tabrizi at the 2020 Huntington's Disease Therapeutics Conference, Palm Springs, CA (photo by Gene Veritas, aka Kenneth P. Serbin)

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.

At Therapeutics Conference, landmark study of young gene carriers highlights how Huntington’s disease researchers seek to solve critical puzzles

Armed with ever more impressive data and a deeper understanding of Huntington’s disease, scientists and drug hunters convened at the 15th Annual HD Therapeutics Conference this week, facing the complex puzzles that still hinder the quest for treatments for this deadly neurological disorder.

One of those puzzles: how to not only treat symptoms, but to prevent them, especially in young presymptomatic carriers of the HD gene, so that they don’t have to spend their lives fearing the currently inevitable onset of this devastating disease.

On February 26, Sarah Tabrizi, FRCP, Ph.D., of University College London, answered key questions about what kinds of health consequences young presymptomatic gene carriers suffer decades before they’re likely to develop the disease in midlife.

Previous studies have demonstrated that brain shrinkage can occur as early as 15 to 18 years before predicted age of onset. Ranging in age from 18-40, the 64 gene carriers in Dr. Tabrizi’s HD Young Adult Study went through state-of-the art brain scans and cognitive testing, and also provided samples of blood and cerebrospinal fluid (CSF) for analysis. These at-risk volunteers are, on average, 24 years from estimated onset.

This study, in line with “The Path to Prevention” (one of five major themes of the 2020 conference), is aimed at helping identify the optimal time to treat gene carriers to slow or prevent their neurological decline.

“Comprehensive cognitive testing was normal,” as compared to 67 non-HD-affected individuals, reported Dr. Tabrizi in her presentation to the conference. “There were no significant psychiatric differences, which I found very interesting, because I would have predicted they would’ve been big differences.”

Dr. Tabrizi said that "there’s always been a thought that carrying the HD gene hard-wired you for psychiatric burden,” but the Young Adult Study suggests that such symptoms become more prominent closer to onset.

“I think that was – and I don’t say this lightly – a landmark presentation,” Robert Pacifici, Ph.D., the chief scientific officer for CHDI Foundation, Inc., the conference sponsor, told me today, adding that Dr. Tabrizi’s team carried out the study with “a high degree of rigor and granularity.”

“The participants seem to be remarkably well,” Dr. Pacifici observed. The absence of many of the neurological and other problems typical of HD is an encouraging prospect for developing safe and well-tolerated treatments that could “not just reverse, but actually prevent” HD, he said.

Dr. Pacifici lauded the study volunteers for their "unbelievably selfless participation," including submitting to the study's "incredibly rigorous battery."

Above, Dr. Sarah Tabrizi presenting her talk on the HD Young Adult Study at the 2020 HD Therapeutics Conference, February 26, 2020, and, below, a closeup of Dr. Tabrizi (photos by Gene Veritas, aka Kenneth P. Serbin)

Overall, ‘good news’ for young gene carriers

The young gene carriers in the study did appear to go through a small change in the area of the forebrain known as the striatum, consisting primarily of the putamen and the caudate, the deep brain regions that are most affected by HD. The striatum helps to control our movements and rewards system.

The study found a significant reduction in the size of the putamen, but an insignificant reduction in the caudate. Nevertheless, Dr. Tabrizi explained that, based on this study, these differences (in comparison with the normal subjects) were “not associated with predicted years to onset.”

“So what we now know, based on the data, is that the striatum never appears to be the same size as the control group,” she explained. 

The “very slightly smaller” striatum may suggest a “neurodevelopmental effect” (the way the brain develops) that is “well compensated for,” Dr. Tabrizi said, meaning that the brain adjusts without clear damage. She added that it “might be why the striatum is vulnerable later in life, because it has a double hit.” As mentioned by Dr. Tabrizi, this interpretation resonates with the research of Peg Nopoulos, M.D., who has studied the compromised development of the brains of people affected by juvenile HD.

Alternatively, neurodegeneration early on could be “too subtle and variable” to associate with predicated age of onset, Dr. Tabrizi noted.

Other imaging results showed no decrease in the white matter (the tissue in the brain made of nerve fibers and possibly involved in cognitive problems in HD) or any other aspect of the brain measured in the study, indicating that the subjects were still “very far from onset,” Dr. Tabrizi continued.

“This is really good news,” Dr. Tabrizi stated.

Douglas Langbehn, M.D., Ph.D., a psychiatrist and biostatistician at the University of Iowa who did the statistical analysis for the HD Young Adult Study, listens to Dr. Tabrizi at the Therapeutics Conference (photo by Gene Veritas).

The ongoing search for reliable biomarkers

The study also involved the ongoing search for reliable biomarkers (signs of disease and drug efficacy).

The study detected mutant huntingtin protein in the subjects’ cerebrospinal fluid. “CSF mutant huntingtin was higher in those closer to [predicted] onset, suggesting that some injury is releasing mutant huntingtin [from the brain], but very subtle,” Dr. Tabrizi said.

Several other biomarkers were elevated in the subjects’ CSF, again indicating an early, subtle injury, but most of those subjects had readings showing levels very close to those of the unaffected control subjects, Dr. Tabrizi continued. Furthermore, six other biomarkers were normal, she added.

The Young Adult Study points to the one CSF biomarker in particular, neurofilament light, a marker of brain damage, as potentially helpful in measuring disease progression and treatment response in people decades from onset, Dr. Tabrizi concluded.

A drug that kept neurofilament light at very low levels could prevent degeneration of the brain, she added.

You can watch Dr. Tabrizi’s presentation in the video below.

A moving keynote address

With a record attendance of 380, the conference opened on February 24 with a moving keynote speech by Amy Merkel, a 45-year-old nurse from Wisconsin and the founder of Starfish Yoga.

A small company, Starfish focuses on encouraging constructive coping skills, primarily for people affected by past imprisonment, sexual abuse, and neurological disorders, including HD.

Amy, who titled her talk “Life is Good,” belongs to a family deeply affected by HD. She recounted her extended family’s decades-long struggles with HD. Amy received a standing ovation.

Stay tuned to this blog for additional reporting on the conference, including an overview provided in my interview with Dr. Pacifici.

Above, HD advocate Amy Merkel addresses the 15th Annual Therapeutics Conference, and, below, poses with researchers Dr. Sarah Tabrizi (far left), Leslie Thompson, Ph.D. (second from right), and Gillian Bates, Ph.D. (photos by Gene Veritas).

New Ionis data show positive trends in clinical measures of Huntington’s disease drug trial volunteers

Exploratory analysis of new data showed positive trends in several clinical signs of Huntington’s disease in the recently concluded Ionis Pharmaceuticals, Inc., gene-silencing Phase 1/2a clinical trial, the company announced April 24.

“Results from exploratory analyses of data from the study demonstrated correlations between reductions in mutant huntingtin (mHTT), the disease-causing protein, and improvements in clinical measures of Huntington's disease,” an Ionis press release stated about its drug IONIS-HTT_Rx.

Initiated in September 2015 and completed in December 2017, the trial tested the drug in 46 symptomatic volunteers at nine sites in Canada, Germany, and the United Kingdom.

Because of the very limited size, duration, and scope of the Phase 1/2a trial, the newly studied clinical signals have only statistical importance. They do not demonstrate whether an individual patient got better, or by how much a person did better on a particular test.

However, they provide hope for the HD community because they showed an association between reducing, or lowering, mHTT, and the improved scores. The new data will help pave the way for the planned Phase 3 trial to test efficacy.

“These important clinical results further demonstrate that targeting the reduction of the toxic mutant huntingtin protein with IONIS-HTT_Rx has the potential to be disease-modifying,” Frank Bennett, Ph.D., Ionis senior vice president of research and franchise leader for neurological programs, stated in the release.

Sarah Tabrizi, FRCP, Ph.D., of University College London, the lead investigator of the Phase 1/2a trial, also presented the new information on April 24 at the annual meeting of the American Academy of Neurology (AAN) in Los Angeles. Out of more than 3,000 submissions, the talk was one of four selected for the top-featured session at the meeting, which drew more than 12,000 professionals.

Checking movements and cognitive loss

On March 1, at the 13th Annual HD Therapeutics Conference in Palm Springs, CA, Dr. Tabrizi revealed that the drop of 40-60 percent in mutant protein observed in the cerebral spinal fluid (CSF). Based on numerous animal studies done by Ionis, that corresponds to to a decrease of 55-85 percent in the cortex of the brain. The cortex is the most developed area of the brain and the source of thought and language, abilities severely hampered by HD. In the caudate – which helps control movement, another critical problem in HD – the corresponding decrease (based on animal data) ranged from 20-50 percent.

The new data demonstrate associations between reduction in mHTT (measured in CSF) and improvement on two clinical tests commonly used in HD clinical studies: the total motor score test (measuring impairments in movements) and the symbol digit modalities test (measuring cognitive loss).

The press release further noted a significant correlation between huntingtin reduction and an improved score on the Composite Unified Huntington's Disease Rating Scale (cUHDRS), which measures decline in patients.

Two tests showed neutral results: the stroop word reading (checking for cognitive loss) and the total functional capacity (assessing ability to perform daily tasks).

A slide from Dr. Tabrizi's talk at the AAN meeting illustrating improved scores in two clinical tests (top two graphs) and neutral scores in two others (bottom graphs) (slide courtesy of Ionis)

Larger, longer studies needed

At the AAN meeting, Dr. Tabrizi emphasized that the three-month Phase 1/2a trial was not designed to measure a true clinical benefit from IONIS-HTT_Rx. It sought primarily to gauge safety and tolerability of the drug.

The researchers used so-called “exploratory post-hoc analysis.”

As explained by Ionis officials in an e-mail, post-hoc means that Ionis did not predefine the analyses in the clinical trial protocol. Such analyses cannot provide conclusive proof of a drug effect. These analyses are common in early-stage clinical trials, where drug companies look for interesting signals worthy of careful evaluation in later-stage trials.

The officials also pointed out that, in analyzing the data using the gold-standard technique for demonstrating effect - comparing clinical test results of drug-treated participants with those on placebo - no improvements were found. This was not a surprise, given the limited scope of a Phase 1/2a trial.

In fact, they added, the trial planners included the clinical tests primarily to monitor for unexpected worsening.

The Ionis officials described the relationship between mHTT-lowering and potential clinical benefit as "subtle."

They emphasized the need for larger and longer trials to demonstrate efficacy.

A 'hint of clinical benefits'

“The measurements were done during the trial, but these statistical analyses were not pre-specified, and so we say that they are post-hoc and exploratory,” Jody Corey-Bloom, M.D., Ph.D., the director of the Huntington’s Disease Society of America (HDSA) Center of Excellence for Family Services and Research (COE) in San Diego, explained in an e-mail.

Dr. Corey-Bloom described the correlations between the clinical measurements and the reduction in the huntingtin protein as “positive but weak. This is very welcome news and clearly in the right direction! We will obviously need larger and longer studies to really confirm a potential clinical benefit, though.”

Swiss pharmaceutical giant Roche, which now holds the license to the Ionis drug, has confirmed that it will take the unusual step of skipping a Phase 2 trial and going directly to Phase 3. Phases 2 and 3 measure a drug’s efficacy. Roche, which renamed the drug RG6042, does not yet have a timeline. (Click here to read more about Roche’s plans.)

"Though press releases and post-hoc analysis can be problematic, the reported improvement in clinical measures in this early clinical trial, if borne out by subsequent study, is a ‘wow’ for the HD community,” LaVonne Goodman, M.D., the founder of Huntington’s Disease Drug Works, commented in an e-mail. “So I look forward to seeing the full data set in a peer-reviewed article. If results from this first trial are borne out in the larger Phase 3 trial, this drug is a game changer for HD. And also great, if results are similar to the present trial, it might take less than the earlier predicted three years to show it.”

“It is quite exciting to see any hint of clinical benefits,” Martha Nance, M.D., the director of the Minneapolis COE, wrote via e-mail. “It is important to know that these clinical results are not definitive, but this report adds to the growing list of favorable results from this groundbreaking trial of gene silencing in HD. The HD community has every right to be excited about these results!”

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For additional coverage of the Ionis news, click here and here.

For HDSA's Q & A on the news, click here.

For background on the development of clinical tests for HD, click here.

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

(This article was updated on April 27, 2018, to include additional comments on the clinical trial analyses by Ionis officials.)

The best news for the Huntington's disease community since the discovery of the gene: Ionis trial data revealed, Roche confirms jump to Phase 3

Researchers revealed impressive, if not conclusive, additional information at CHDI Foundation's 13th Annual Huntington’s Disease Therapeutics Conference yesterday regarding the historic Ionis HD clinical trial: the drop in mutant protein observed in the cerebral spinal fluid (CSF) of participants corresponds to as much as an 85 percent decrease in the cortex of the brain, head physician Dr. Sarah Tabrizi announced.

It’s the best news the HD community has received since the publication of the research confirming the discovery of the gene 25 years ago this month. As scientists have observed, it’s also a major step for disease and drug research in general.

“The magnitude of mutant huntingtin [protein] reduction observed exceeds the effect needed for disease modification in animal models,” Dr. Tabrizi, of University College of London (the lead clinical trial site), told an audience of some 350 scientists, drug company representatives, and HD advocates at the conference in Palm Springs, CA.

Dr. Sarah Tabrizi presenting the IONIS-HTTRx trial data on March 1, 2018 (photo by Gene Veritas, aka Kenneth P. Serbin)

Ionis officials announced in December that the Phase 1/2a trial for the gene-silencing drug IONIS-HTT_Rx “substantially exceeded our expectations” in safely reducing the mutant huntingtin in the CSF.

For the first time, Dr. Tabrizi’s presentation (plus an Ionis press release) specified the level of huntingtin reduction.

During the clinical trial, participants received the drug via spinal injections, and doctors measured the drug’s ability to reduce the protein by extracting CSF samples.

IONIS-HTT_Rx lowered mutant huntingtin an average of 40 percent, with a maximum reduction of 60 percent. As Dr. Tabrizi explained, projecting from the numerous, painstaking animal studies done by Ionis, the reductions in the cortex range from 55-85 percent.

Frank Bennett, Ph.D., Ionis senior vice president of research and the franchise leader for neurology programs (left) and Anne Smith, Ph.D., Ionis director of clinical development (middle), confer with Dr. Tabrizi moments before the two women's historic presentation of the IONIS-HTTRx trial data. Dr. Bennett led the Ionis efforts to develop the drug (photo by Gene Veritas).

The cortex – along with the striatum, which is critical to motor control and managing the reward system – is the area of the brain most affected by HD. It is the most developed area of the brain, the source of thought and language, abilities severely hampered by HD.

Watch Dr. Tabrizi in the short video excerpts below explain this data and thank the 46 brave clinical trial volunteers and the many others involved in the effort. I also recommend watching the full video – which includes further trial data and a helpful overview of the project by Anne Smith, Ph.D., of Ionis – by clicking here.

 Ionis trial reduces bad Huntington's disease protein from Gene Veritas on Vimeo.

The plans for RG6042, the drug’s new name

The presentation by Drs. Smith and Tabrizi – the first public presentation of the trial data – can perhaps help inspire the HD community and researchers to become engaged in the next, crucial step: testing the drug’s efficacy.

Based on its partnership agreement with Ionis, Swiss pharmaceutical giant Roche, which now holds the license to the drug, will carry out a longer trial with hundreds of participants, including sites in the U.S.

The main question: will symptoms of this progressive, deadly disease stabilize, or even be reversed?

In an interview at the conference, Roche officials told me that – as Ionis had indicated – the company would take the unusual step of skipping a Phase 2 trial (testing efficacy for the first time) and going directly to a Phase 3 (confirming efficacy in hundreds, or more, participants).

They pointed to the excellent results of the Phase 1/2a trial; Ionis’ superb development of the drug; the nonprofit CHDI’s expertise and leadership; and the enthusiasm from – and urgent need of – the HD community.

Roche has officially changed the name of IONIS-HTT_Rx to RG6042. “R” stands for Roche, and “G” for Genentech, a major U.S.-based pharmaceutical company acquired by Roche in 2009 for $46.8 billion. The number 6042 is a standard drug number assigned by the company. If Phase 3 is successful, a drug issued for commercial sale will get a brand name.

All U.S-based Roche personnel and products still use the name Genentech.

Roche has not yet determined a start date or timeline for Phase 3. I will provide a detailed report on the interview and Roche’s plans, and also my personal reactions to the conference, in upcoming articles.

Members of the Roche HD clinical trial team watch Dr. Tabrizi's presentation. From left to right, Scott Schobel, M.D., M.S., clinical science leader of product development; Lauren Boak, Ph.D., global development team leader; Erik Lundgren, lifecycle leader of the HD program; and Mai-Lise Nguyen, the patient partnership director for the HD program (photo by Gene Veritas). 

Time for excitement, but also caution

CHDI Chief Scientific Officer Robert Pacifici, Ph.D., called the results of the Ionis trial “incredibly exciting.”

However, he also cautioned the HD community.

“Drug discovery is a really time-consuming and inefficient process, and, sadly, fraught with many failures,” Dr. Pacifici said. “The first time you put something into people, no matter how prepared, you never know whether it’s going to be safe and well-tolerated. What the initial trial showed was that at those doses, with the route of delivery, with that population of folks, it is indeed safe and well-tolerated. (If it wasn’t, it would stop in its tracks.) Once you get to this stage, a lot of the uncertainty about timelines goes away.

“This is really the time to be incredibly careful and incredibly deliberate. It’s going to take a while now to orchestrate the Phase 3 trial. That’s the pivotal trial that tells you whether or not the drug works.”

Everything needs to be done “by the book” to get a really “conclusive result,” he added.

If the trial fails, it will still provide scientists and physicians with guideposts for future research and trials, he said.

“We owe a huge debt of gratitude to those patients who signed up for that initial trial,” Dr. Pacifici concluded. “It’s going to require not only more of that type of participation, but a lot of patience.”

You can watch my interview with Dr. Pacifici about the conference and the Ionis trial in the video below.

 A time for excitement, but also great care and deliberation from Gene Veritas on Vimeo.

* * *

Ionis hosted a live webcast at 11 a.m. Eastern Time today. A webcast replay, including slides with clinical trial data, are available by clicking here.

For detailed coverage of the HD conference presentations, visit hdbuzz.net.

Visit my Vimeo album, to be periodically updated in the coming weeks, for other presentations and interviews at the conference.

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