Top 10 Huntington’s Disease Stories of 2021

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by Marta Figueiredo, PhD |

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Throughout 2021, Huntington’s Disease News brought you daily coverage of the latest scientific findings, treatment developments, and clinical trials related to Huntington’s disease.

As a reminder of what mattered most to you last year, here are the top 10 most-read articles of 2021 with a brief description of what made them interesting and important to the Huntington’s community.

We look forward to reporting more news relevant to patients, family members, and caregivers dealing with this disease in 2022.

No. 10 – “Enrollment Now Complete for PROOF-HD Trial of Oral Pridopidine

In November, Prilenia Therapeutics announced it had completed enrollment for the Phase 3 PROOF-HD clinical trial (NCT04556656) testing its investigational oral therapy pridopidine in adults, 25 and older, with early stage Huntington’s. With nearly 500 patients enrolled, the trial, taking place in North America and Europe, surpassed its initial target, and ahead of schedule.

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Pridopidine works by selectively activating a receptor protein involved in several key pathways that maintain neuronal health and function. One such pathway involves a neuroprotective protein called brain-derived neurotrophic factor, whose levels are reduced in people with Huntington’s.

The study seeks to assess whether 1.5 years of treatment with pridopidine is superior to a placebo at preventing or slowing functional decline, as well as easing motor and behavioral symptoms. Top-line results are expected in the first months of 2023.

No. 9 – “FDA Places Prilenia’s Oral Pridopidine on Fast Track

Also in November, the U.S. Food and Drug Administration (FDA) granted fast track designation to pridopidine for the treatment of Huntington’s. The therapy had previously received orphan drug designation in the U.S. and Europe for the same indication. All these designations are meant to expedite pridopidine’s clinical development and regulatory review. Data from previous trials showed that the therapy, taken orally twice a day, significantly and sustainably prevented functional decline in people with early stage Huntington’s, relative to a placebo.

No. 8 – “COVID-19 Vaccines Pose Little Risk to Rare Disease Patients, FDA, CDC Say

In early 2021, we reported the main messages of a COVID-19 vaccine-centered webinar hosted by the National Organization for Rare Disorders and involving officials from the FDA and the Centers for Disease Control and Prevention. Regarding the Pfizer and the Moderna vaccines — which at that time had recently been granted emergency use authorization in the U.S. — Peter Marks, MD, PhD, the director of the FDA’s Center for Biologics Evaluation and Research, said that there was “clear and compelling evidence that they are safe and effective.”

While it is difficult to study these vaccines for each rare disease due to the limited number of patients, available evidence strongly suggested that COVID-19 vaccines would cause no harm to those with a rare disease, Marks said. He also emphasized that both vaccines showed strong, comparable efficacy and safety, with the best vaccine being the one that patients could get sooner.

No. 7 – “SAGE-718 on FDA Fast Track as Potential Huntington’s Therapy

In September, SAGE-718, Sage Therapeutics’ experimental oral therapy for Huntington’s, was given fast track designation by the FDA. SAGE-718 is a first-in-class modulator of the activity of the N-methyl-D-aspartate receptor, a protein found at the surface of nerve cells and that plays key roles in learning and memory.

Results from previous small trials involving people with Huntington’s and other neurodegenerative diseases showed that SAGE-718 treatment was associated with improved cognitive performance. Based on these promising findings, Sage launched a placebo-controlled Phase 2 trial (NCT05107128) to assess whether SAGE-718 improves cognitive function in up to 178 adults with early to moderate Huntington’s.

No. 6 – “Safety Seen in AMT-130 Gene Therapy Trial, Six More Patients to Enroll

In February, uniQure announced that no significant safety concerns were observed in the first four Huntington’s patients enrolled in a proof-of-concept Phase 1/2 trial (NCT04120493) testing its investigational gene therapy, AMT-130. It uses a modified and harmless virus to deliver a small RNA molecule that specifically suppresses the production of the abnormal huntingtin protein that drives Huntington’s development. Two of these participants received a low dose of AMT-130 directly into the brain, while the other two underwent a sham brain procedure.

Based on these findings, the trial’s data safety monitoring board allowed recruitment to continue for this low-dose group, expected to include a total of 10 patients. If no safety concerns are observed with this dose, an additional 16 patients are expected to be enrolled for the high-dose group. The trial is still recruiting at more than 10 U.S. sites.

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No. 5 – “Women with Huntington’s Experience Worse Symptoms Than Men, Global Study Suggests

Researchers in the U.S. found that women with Huntington’s disease have worse motor, cognitive, and depressive symptoms than men with the condition. These findings were based on data from more than 8,000 Huntington’s patients who were followed for four years in the international Enroll-HD observational study (NCT01574053). Participants’ demographic information and data about their motor, cognitive, and behavioral function were retrospectively analyzed.

Results also showed that there were no sex-specific differences in terms of patients’ age at diagnosis and symptom progression over time. These findings may help to increase awareness of the clinical differences between women and men with Huntington’s, which may improve care and help better understand the disease’s underlying mechanisms.

No. 4 – “Pridopidine Analysis Shows Slowed Decline in Total Functional Capacity

Prilenia’s pridopidine safely and effectively slowed functional decline in people with Huntington’s, according to data from the placebo-controlled Phase 2 PRIDE-HD trial (NCT02006472) and the open-label extension OPEN-HART (NCT01306929) study. Specifically, a post hoc analysis (an analysis done after the trial is over) of PRIDE-HD, which tested several pridopidine doses against a placebo in 408 patients, showed that 45 mg of pridopidine twice per day, which is expected to be the most effective dose, was associated with a stabilization of total functional capacity (TFC) scores over one year. In turn, participants given a placebo showed a gradual TFC score drop, indicative of worse functionality. This group difference was even more pronounced among patients with early-stage disease.

Results from OPEN-HART, in which participants of PRIDE-HD and other pridopidine trials received the therapy for longer periods, showed that the oral therapy was generally safe over five years. It also significantly slowed functional decline when compared with historical data from untreated Huntington’s patients.

No. 3 – “AMT-130 Gene Therapy Appears Safe; More Data Forthcoming

In September, uniQure announced that AMT-130 continued to show a favorable safety profile in the first eight Huntington’s patients given the gene therapy in its Phase 1/2 trial. Six of them received the low dose of AMT-130 and two received the high dose. In parallel, six additional participants underwent a sham procedure, four in the low-dose group and two in the high-dose group. The trial’s data safety monitoring board was expected to review updated results before year’s end to decide whether the study could recruit the final 12 patients in the high-dose group. After one year, participants given the sham procedure may be eligible to receive the gene therapy, pending a data review by the monitoring board and the FDA.

The trial’s top-line data are expected by the end of 2022, and the study is estimated to finish by May 2026. Findings from this and a similar European Phase 1b/2 trial are expected to confirm the therapy’s potential and establish its optimal dose to be evaluated in a larger, future trial.

No. 2 – “VO659 Earns Orphan Drug Designation

In August, the FDA granted orphan drug designation to Vico Therapeutics’ experimental therapy VO659 for Huntington’s. The therapy previously received a similar designation in Europe.

VO659 is an antisense oligonucleotide that works by suppressing the generation of the huntingtin protein. It does so by binding to and blocking an intermediate molecule derived from DNA that guides huntingtin production. By reducing the levels of mutant huntingtin, VO659 may have the potential to slow or halt Huntington’s progression. The therapy has not yet been tested in human clinical trials.

No. 1 – “Dosing Stopped in Phase 3 Trial of Tominersen for Huntington’s, Roche Says

Our most-read article of 2021 concerned Roche’s announcement, in March, that dosing of tominersen, its investigational therapy for Huntington’s disease, had been discontinued in the Phase 3 GENERATION HD1 trial (NCT03761849). Dosing in GEN-EXTEND (NCT03842969), an open-label extension study for people who participated in other tominersen trials, was also paused.

The antisense oligonucleotide therapy, administered directly into the spinal canal, was designed to suppress the production of all huntingtin forms, including the mutated variant that leads to the disease. After promising Phase 1/2 results, Roche launched GENERATION HD1, which was evaluating tominersen’s two-year safety and effectiveness in nearly 800 Huntington’s patients, 25 to 65 years old.

Roche’s decision was made after an independent data monitoring committee issued a “no go” recommendation based on the therapy’s potential benefit/risk profile. While at the time Roche noted only that no new safety concerns had been identified, the company later presented 1.5-year data from GENERATION HD1 that showed tominersen was not conferring any benefit to patients relative to a placebo.



At Huntington’s Disease News we hope these stories and our reporting throughout 2021 helped to better inform and improve the lives of everyone affected by Huntington’s.

We wish all our readers a happy 2022.