Two recent press releases from uniQureprovide welcome good news: the first ever Huntington’s Disease (HD) gene therapy, known as AMT-130, has been administered via brain surgery to a small set of participants in an early safety trial. At the same time, uniQure has published findings in HD animal models that increase confidence in the drug’s ability to lower huntingtin, especially in parts of the brain most affected by HD.
The first gene therapy for HD
Gene therapy is a technique to introduce, replace, or remove genetic material from a person’s cells to treat a disease. In the case of Huntington’s disease, current gene therapies seek to inactivate the faulty message (RNA) produced by the HD gene, ultimately lowering the amount of huntingtin protein in the brain or body. There are dozens of research laboratories and companies working on different approaches to this, but uniQure’s HD gene therapy, AMT-130, is the first to be tested in humans.
Unfortunately, I have to share sad news on the promising clinical trial on the drug Tominersen.
This statement is from Roche/Genentech on March 22, 2021. From David West, on behalf of the Roche/Genentech HD team Senior Director, Global Patient Partnership
Dear global HD partners,
As part of our ongoing partnership and following your request to receive important and timely updates about Roche’s HD clinical programme, we wanted to share an important update with you.
We have tough news to share, and we recognise that it will be even more difficult to receive.
Throughout the Phase III GENERATION HD1 study of tominersen in manifest Huntington’s disease (HD), an independent data monitoring committee (iDMC) has been in place. This committee is separate from Roche and Genentech and regularly reviews incoming clinical study data (that Roche and Genentech do not have access to) to review patient safety and assess the balance of potential risk versus potential benefit for study participants. The committee recently met for a pre-planned review of the latest safety and efficacy data from GENERATION HD1 and made a recommendation about the investigational therapy’s potential benefit/risk profile. Based on the committee’s recommendation, we will permanently stop dosing with tominersen and placebo in the GENERATION HD1 study. It is important to note that the recommendation is not based on any new emergent safety concern, but on a broad assessment of the benefit/risk of the treatment arms compared to the placebo arm over time.
Unfortunately, whilst this will raise questions in the community, we do not yet have access to the data from this study. What we can share with you at this time is provided in this letter and in our press release. Please find our press release here.
The nonprofit, Huntington’s Disease Society of America (HDSA), mission is dedicated to improving the lives of everyone affected by Huntington’s disease (HD). HD is a rare, fatal, genetic brain disorder that has the symptoms of ALS, Alzheimers and Parkinson’s at the same time and there is NO CURE. What is HD?
On Saturday, November 2nd, Stanford University will host a Huntington’s Disease Symposium.
This event was created for patients with Huntington’s disease and their families or others who would like to learn more about the disease. This symposium will highlight current research and experimental therapies, measures that improve health including nutrition, exercise, and physical therapy strategies to improve psychiatric and cognitive challenges in Huntington’s disease and ways to support the patient and families.
The symposium will highlight experts from Stanford Center of Excellence.
The HDSA Centers of Excellence provide an elite team approach to Huntington’s disease care and research. Patients benefit from expert neurologists, psychiatrists, social workers, therapists, counselors and other professionals who have extensive experience working with families affected by HD and who work collaboratively to help families plan the best HD care program throughout the course of the disease. Applications to become an HDSA Center of Excellence are open to all clinics in the United States who share HDSA’s commitment to high-quality, comprehensive care and access to clinical research.https://hdsa.org/find-help/clinical-care-services/hdsa-centers-of-excellence/
In 1983, Orphan Drug Act (ODA) was set up to encourage increased development of drugs for rare diseases. It was amended in 1984 to define rare diseases as those that affect less than 200,000 people in the United States, but it also included drugs for diseases affecting more than 200,000 people as long as there was no commercial viability—that is, that the cost of development and making available in the United States a drug for the disease would exceed revenue from the US sales. Huntington’s disease fits that criteria. Overview-of-huntingtons-disease/
Wave Life Sciences has seen the FDA grant it an orphan drug designation for its lead candidate WVE-120101. The experimental drug, which targets rs362307–a single nucleotide polymorphism that is associated with the disease-causing mutation in the huntingtin gene.
The orphan status gives it 7 years of exclusivity in the U.S., and other boosts, including tax credits related to clinical trial expenses, an exemption from the FDA user fee, and FDA assistance in clinical trial design.
Another Sponsor at the Huntington’s Disease Society of America in Boston last June was Vaccinex, Inc.
Vaccinex and the Huntington Study Group (HSG) launched a trial for people with the gene mutation that causes HD who are either early in the progression of the disease or are not yet diagnosed with the disease.
SIGNAL, a Phase 2, multi-center, randomized, double-blind, placebo controlled study in subjects with early manifest and late prodromal Huntington’s disease (HD) to assess the safety, tolerability, pharmacokinetics, and efficacy of VX15/2503 (pepinemab). Pepinemab a monoclonal antibody that is a potential treatment for Huntington’s disease (HD). What-is-hd/overview-of-huntingtons-disease/
On January 16, 2019, Vaccinex, Inc. announced the enrollment was complete and includes two cohorts with a total of 265 Huntington’s Disease subjects – 179 in group 1 (B1) who have early manifest disease and 86 in group 2 (B2) who are late prodromal. All subjects are randomized to receive monthly infusions of either VX15/2503 (pepinemab) or placebo for 18 months in double-blind fashion without crossover.
“The U.S. Food and Drug Administration (FDA) has completed its review of our Investigational New Drug (IND) application for AMT-130, allowing us to begin our planned Phase I/II study. We expect that in the second half of 2019 AMT-130 will be the first ONE-TIME administered AAV gene therapyto enter clinical testing for the treatment of Huntington’s disease.” To read about the clinical trial, visit http://uniqure.com/gene-therapy/huntingtons-disease.php
uniQure’s gene therapy candidate for Huntington’s disease is differentiated in that:
AMT-130 targets the deep brain structures known for the disease pathology onset.
AMT-130 silences mutant huntingtin protein at levels not demonstrated in other studies.
AMT-130 targets the accumulation of the exon 1 HTT fragment, the most toxic source of abnormal protein aggregation in Huntington’s disease.
The AMT-130 trial will be based at HD clinical sites in the Unites States. It’s not known at this time what sites or how many, yet. These will be publicly announced when they come online. UniQure hopes to begin enrolling patients before the end of 2019. It is brain surgery. https://en.hdbuzz.net/274
At this time, in the Huntington’s disease arena around the world, people are needed to participate in the exciting clinical trials being conducted. Without people, very brave people, we cannot move forward in finding a cure for the cruelest disease on the planet; Huntington’s disease (HD).
Enroll-HDis a longitudinal, observational, multinational study that will integrate two existing Huntington’s Disease (HD) registries, REGISTRY in Europe and COHORT in North America and Australia, while also expanding to include sites in Latin America and Asia. With no end date and annual assessments, the goal of Enroll-HD is to build a large and rich database of longitudinal clinical information and biospecimens. This database will serve as a basis for future studies aimed at developing tools and biomarkers for progression and prognosis, identifying clinically relevant phenotypic characteristics, and establishing clearly defined endpoints for interventional studies. To learn more about Enroll-HD, go to: https://www.enroll-hd.org/
The idea is that this one study will make all other HD research easier, speeding up the process of developing new drugs and other treatments that really work. Rather than being restricted to a select group of researchers, it will be a resource for all HD science, making it faster and more efficient for other researchers to conduct their projects. This is why it’s called a platform, it supports other work.