On 2 june, the EHA, in collaboration with Novartis, organised an informative webinar to present INVEST-HD, which is currently in the process of recruiting participants for its Phase 3 trial with the aim of further evaluating the efficacy and safety of votoplam in people with HD. Approximately 770 people living with Huntington’s disease are expected to participate in the study worldwide.
Novartis is driving forward the development of Votoplam as a potential treatment for Huntington’s disease. The drug, formerly known as PTC518, was initially developed by PTC Therapeutics. In December 2024, Novartis and PTC Therapeutics signed a licensing and collaboration agreement to continue its development.Â
The study is evaluating Votoplam, an oral HTT mRNA splice modifier that reduces the production of mHTT protein. The effect of Votoplam on HTT mRNA promotes the inclusion of an extra exon during transcription, which results in reduced production of both mutant and normal HTT protein. The treatment is administered orally.
During the webinar, Beth Borowsky and Åsa Petersén, explained the development of Votoplam to date, its mechanism of action, the study design, as well as the inclusion criteria and assessments, and the practical implications that participation in the study will have for the patients included in it.
Following the presentation, a live question-and-answer session took place during which the researchers addressed the main queries raised by attendees. These were some of the most relevant topics.
The INVEST-HD clinical trial will be conducted in at least 30 countries around the world, including several European countries. Participating countries and centres are being recruited on a rolling basis, as both the regulatory authorities in each country and each research centre must meet and exceed a series of requirements before they can take part in the study.
So far, the first countries to start the trial have been the United States, Canada and the United Kingdom, where there are already 13 active clinical centres. As new countries and centres obtain the necessary approvals, their participation will be published on ClinicalTrials.gov. Anyone interested can also check this information with their doctor or healthcare team to find out whether any centres in their area will be taking part in the study.
According to those in charge of the study, the large number of participants is intended to provide a clear and conclusive answer regarding the efficacy of votoplam.
By including people with Huntington’s disease at very early stages, when the progression of the disease is slower, it is necessary to monitor a larger number of participants over a sufficiently long period of time to be able to detect whether the treatment succeeds in slowing that progression. The sample size has been determined by statistical analysis to ensure that the trial can provide a definitive answer, although interim analyses are planned.
All assessments and instructions for the digital tools will be provided in the local language of each participating country. The study will include MRI scans to monitor both the progression of the disease, by tracking brain atrophy, and the safety of participants, enabling the detection of any potential changes or warning signs.
In addition, blood and urine samples will be collected. These will be used primarily for the standard safety analyses carried out in a clinical trial, such as monitoring biochemical parameters and pregnancy tests for women of childbearing age. The samples will also enable the analysis of disease-related biomarkers, including the measurement of huntingtin levels in the blood, as well as other markers that may provide information on the progression of the disease.
The development of votoplam is taking place at a time of very active research into Huntington’s disease, with multiple therapeutic approaches currently under investigation.
Unlike other strategies, such as gene therapies administered directly into the brain or treatments involving injections into the cerebrospinal fluid, votoplam is an oral treatment in the form of a tablet taken once daily, which offers a less invasive and easier-to-use route of administration.
Furthermore, although many of these treatments share the aim of reducing huntingtin protein or targeting different mechanisms of the disease, each one addresses different aspects of its biology. Taken together, these complementary approaches reflect an expanding field, in which several therapeutic options could eventually coexist depending on the stage of the disease and the needs of each patient.
The first recommendation is to speak to your regular doctor or GP, particularly if you are at an early stage without any functional impairment. You can also search for your nearest centre of excellence via the public Enroll-HD network or check for updates on centres and their contact details directly on the ClinicalTrials.gov platform. Finally, another key option is to contact patient organisations, such as the European Huntington’s Association (EHA), which actively monitor these studies and provide search tools and information to guide families towards authorised centres, like our website hdtrialfinder.net ; it is worth noting that on this occasion the study will be expanded to include countries not usually involved in this type of research, opening up new opportunities for participation in more regions, like Israel, China or Taiwan…
While studying branaplam as a splice modulator for spinal muscular atrophy (SMA) in babies, Novartis discovered it also targeted Huntington’s mRNA, prompting a clinical trial for Huntington’s disease. Although the drug successfully lowered Huntington protein levels, the trial was stopped early due to signs of peripheral neuropathy. However, researchers caught this side effect very early using a biomarker called NFL (neurofilament light chain), which has now become a standard safety measure across the industry for all splice modulators.
Compassionate use is not available at present. This program only applies to medicines that have already been approved and are marketed in at least one country worldwide. Given that the treatment in question is at a very early stage of research (Phase III trial) and its benefit-risk profile has not yet been fully established, it is not legally possible to apply for it on humanitarian grounds.
We would like to remind you that you can keep up to date with this study on the website at HDTrialFinder and at ClinicTrials.gov study details.
– Article written by Ruth BlancoÂ