Claudia Azañedo – HDTrialFinder

A Rollercoaster Ride to Hope

Claudia Azañedo — Tue, 07 Jul 2026 16:22:48 +0000

A Rollercoaster Ride to Hope

The AMT-130 Story, and What the FDA's June 2026 Announcement Means for Our Community

Our community’s first meeting with the pharmaceutical company uniQure took place in September 2018. At the time, the idea that a gene therapy could actually slow HD felt like pie in the sky. Nearly eight years later, on June 17, 2026, that hope took a major step toward becoming real.

This update walks through that journey — the excitement, the setbacks, and the advocacy that helped get us here — and what it means going forward.

What is AMT-130?

Gene therapy aims to treat disease by changing the genetic instructions inside our cells. Imagine your DNA is a cookbook. If one recipe contains a mistake, gene therapy works like an editor, correcting or blocking the faulty recipe.

AMT-130 is designed to reduce production of the harmful huntingtin protein that causes HD. It uses a harmless virus to deliver a small genetic molecule into the brain that “switches down” the faulty huntingtin gene. The treatment is given once through MRI-guided brain surgery and has been tested at both a low and a high dose.

So far, AMT-130 has been studied in two Phase I/II clinical trials:

United States: Began in June 2020. Participants were randomly assigned to receive either AMT-130 or a sham (imitation) brain surgery.
Europe: Began in February 2022 in Warsaw, Poland, and later expanded to sites in the UK. Everyone in this study received AMT-130.

The Journey So Far

September 24, 2025 – Landmark results
Three years after treatment, people who received the high dose of AMT-130 showed a 75% slowing in disease progression compared with matched external controls alongside favourable biomarker changes. You can read more here.
November 3, 2025 – A difficult reversal
Following an October 29 pre-submission meeting, the FDA told uniQure it no longer agreed that the trial data — compared against that matched “external control” group rather than an internal placebo group — were sufficient, on their own, to support a Biologics License Application (BLA), the formal request to market AMT-130 in the US.
This was a major disappointment. A new trial would require more volunteers to undergo brain surgery without receiving the treatment, raising serious ethical concerns for this fatal, progressive disease where every year of delay matters.
Late 2025 to January 2026 – The community responds
As they say, “you can’t keep a good man down”: patient advocacy groups in the US quickly mobilised and started 2 petitions which were signed worldwide. On January 22, 2026, with the petitions having gathered more than 48,000 signatures, representatives hand-delivered them to FDA alongside more than 11,000 messages sent to Congress.The petitions called on the FDA to honour its prior guidance and expedite review by allowing uniQure to file a BLA for accelerated approval consideration for its investigational gene therapy, AMT-130
Community representatives also secured a place in discussions with the FDA, helping ensure patients’ voices were heard.
March 2, 2026 – The setback confirmed
The FDA confirmed its position, saying the existing data were still not enough for approval and again recommending a new randomized, sham-controlled trial.
April 30, 2026 – Progress in the UK
While discussions continued in the US, uniQure announced a positive meeting with the UK’s Medicines and Healthcare products Regulatory Agency (MHRA). The company confirmed plans to apply for UK approval in the third quarter of 2026.
June 17, 2026 – A turning point
In a major reversal, the FDA and uniQure reached a breakthrough alignment. The FDA agreed to allow uniQure to submit an application for accelerated approval based on the totality of their existing Phase I/II data and three-year follow-up, bypassing the need for a highly controversial sham-surgery study. Read the press release here.

What Happens Next?

It’s important to understand what this does—and doesn’t—mean.

AMT-130 is still experimental. It has not yet been approved and is only available through clinical trials.
The FDA application has not yet been submitted. uniQure expects to file it in Q3 2026, after which the FDA review process will begin.
Accelerated approval is conditional. If granted, it would allow earlier patient access while requiring a follow-up study to confirm the treatment’s long-term benefit.
The UK review is happening separately. uniQure also plans to submit its application to the MHRA during Q3 2026.

Even with these important steps still ahead, June 17, 2026 represents a genuine milestone. The achievements are thanks to the trial participants who volunteered for brain surgery, the researchers who continued pushing forward, and a community that refused to give up when the path became more difficult.

For the first time, a treatment has shown in people that it may be possible to slow the progression of Huntington’s disease.

– Article written by Dina de Sousa

AN UPSIDE DOWN APPROACH TO CLINICAL TRIALS

Claudia Azañedo — Fri, 19 Jun 2026 12:06:03 +0000

SKYHAWK THERAPEUTICS

AN UPSIDE DOWN APPROACH TO CLINICAL TRIALS: LEADING TO SOME EXCITING RESULTS

Skyhawk Therapeutics, a US-based pharmaceutical company, has developed a new medication that aims to slow the progression of Huntington’s Disease. Let’s start from the beginning and go through Skyhawk’s timeline:

SKY-0515 is taken as a once-daily pill by mouth. It is designed to lower the levels of two harmful proteins linked to HD (Mutant huntingtin(mHTT) and PMS1). You can read more in regards to this approach in our article published September 18, 2025.

1) Huntingtin protein. In people with HD, the huntingtin gene carries a fault (mutation) that causes the body to produce an abnormal version of the huntingtin protein, called mutant huntingtin (mHTT). This abnormal protein is what drives the disease. SKY-0515 lowers levels of both the normal and the mutant form of huntingtin.

2) PMS1 protein. PMS1 plays a role in a process called “somatic expansion.” To understand this: everyone with HD is born with a certain length of genetic repeat in their huntingtin gene, but in some cells — especially brain cells — that repeat gradually gets longer over a person’s lifetime. This lengthening is called somatic expansion, and research suggests it may influence when symptoms first appear. By lowering PMS1, SKY-0515 may help slow this process. Somatic expansion is one of the most actively studied areas in HD research today.

Phase 1 trial

Skyhawk chose to take a different path from other pharmaceutical companies and begin their clinical trials, Down Under, in Australia and New Zealand.

The Phase 1 trial had three parts. Parts A and B enrolled healthy volunteers who do not carry the HD gene mutation. Part C enrolled people living with HD. The main goal was to check that the drug is safe and well tolerated by the body.

On 27 January, Skyhawk announced results from a 9-month interim analysis (a planned look at the data while the trial is still ongoing) of Part C participants in the Phase 1 trial.

Key findings included:

SKY-0515 was safe and well tolerated.
Participants taking SKY-0515 showed reductions in mutant huntingtin levels in blood that were “dose-dependent” — meaning the higher dose produced a greater reduction than the lower dose.
At the higher dose, average reductions of about 62% in mutant huntingtin were seen
Levels of PMS1 were reduced by about 26%, but there is not yet enough data to know whether this reduction is large enough to meaningfully slow somatic expansion.
The drug was shown to reach the brain, which is essential for any treatment targeting HD.

Phase 2/3 trial — FALCON-HD

Based on the promising interim results from Phase 1 the company then started a Phase 2/3 trial called FALCON-HD. The company yet again began with sites in Australia and New Zealand. Proceeding with 2 sites in the country of Georgia. A different approach to site selection reflecting a broader global approach to recruitment

As noted by Masoud Mokhtarani, Senior Vice President of Clinical Development, “Based on global feasibility assessments, sites in Georgia were selected due to their strong clinical research infrastructure, access to the target patient population, and limited competition from other ongoing clinical trials.”

The Phase 2/3 trial is designed both to find the best dose and to test whether the drug has a meaningful effect on HD symptoms.

FALCON-HD is enrolling people at stages 2 and 3 of HD, as defined by the HD Integrated Staging System (HD-ISS). This is a newer way of classifying how far HD has progressed, currently used only in clinical trials rather than in everyday medical practice. The trial aims to enrol around 520 participants in total. Each participant is randomly assigned to receive either SKY-0515 (at one of three different dose levels) or a placebo, The drug is taken as a once-daily pill for at least 12 months.

As well as continuing to monitor safety, FALCON-HD is designed to measure whether SKY-0515 has a meaningful effect on the signs and symptoms of HD. Researchers are also tracking biological markers to see whether the drug affects levels of huntingtin and PMS1 proteins in the body.

Provisional approval pathway in Australia

On 3 March, Skyhawk announced that Australia’s Therapeutic Goods Administration (TGA) — the Australian equivalent of the EMA or FDA — has determined that SKY-0515 meets the eligibility criteria for its “provisional approval” pathway. This is a regulatory route that can allow earlier access to a promising medicine based on preliminary clinical data, before full Phase 3 trials are completed. Skyhawk is in the process of submitting a formal application to the TGA. It is important to note that this milestone does not guarantee that the drug will be approved or made available — it simply means the process for an early review has begun.

On June 1st, Skyhawk announced results from a 12-month interim analysis from the Phase 1 trial providing further insights into the potential of SKY-0515 (press release).

As with the 9 months results treatment resulted in a dose-dependent reduction in mutant huntingtin(mHTT) protein in blood of up to to 69% – the largest reduction reported so far in any HD clinical trial
Reductions on PMS1 mRNA of up to 26%

At 3, 6, 9, 12 months, participants demonstrated positive mean changes from baseline Composite Unified Huntington’s Disease Rating Scale(cUHDRS).
Favourable trends were also observed across all cUHDRS subcomponents, including Total Motor Score, Total Functional Capacity, Symbol Digit Modalities Test and Stroop Word Reading Test.
The Company also announced that the Australia and New Zealand portion of its Phase 2/3 FALCON-HD trial completed enrolment 6 months ahead of schedule with 144 patients enrolled
The worldwide Phase 2/3 FALCON-HD trial has expanded to 8 countries

Looking ahead

Although still in development, SKY-0515 and the FALCON-HD trial represent an important step forward in the search for disease-modifying therapies for Huntington’s disease.

This study brings new hope for the HD community as researchers continue to explore treatments that target the underlying biology of the disease.

More details are available at Clinical Trial NCT07378644 and www.falcon-hd.com.

Read the full press release here.

– Article written by Dina de Sousa

– Illustrations by EHA Communication Team