The Risks and Benefits of Clinical Trials for Pre-symptomatic HD Patients

In my previous column, I shared that the U.S. Food and Drug Administration (FDA) accepted the request submitted by my fellow advocates and me to host a patient listening session focused on people who are gene-positive for Huntington’s disease (HD), but have not yet developed symptoms.

Our session is scheduled for Monday, July 25, and we are in full planning mode. In addition to the six speakers who will share their stories and desires, the FDA has asked to hear about the risks pre-symptomatic individuals are willing to take, and what the potential benefits of those risks might be.

Over the past month, I’ve been thinking and talking with others about what benefit and risk mean when it comes to Huntington’s disease.

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Currently, there are no available treatments to slow or halt HD progression. There are a handful of clinical trials underway that aim to accomplish this, but we don’t yet know if the FDA will approve the therapies. The process required to develop treatments for pre-symptomatic individuals is particularly complex, but I’ll do my best to explain it.

For a therapy to be approved by a regulatory body like the FDA or the European Medicines Agency, researchers must demonstrate that it’s safe and effective. While no disease-modifying therapies have been approved for HD, there are several treatments that can help with symptom management. For instance, Austedo (deutetrabenazine) and Xenazine (tetrabenazine) are used to treat chorea, or involuntary muscle movements. These medicines were approved based on clinical trials that measured a patient’s symptoms using the Unified Huntington’s Disease Rating Scale, a tool that allows physicians to assess and rate clinical features of HD.

In the clinical trials for these medicines, researchers essentially rated the severity of patients’ chorea, had them take the medicine, then reevaluated their chorea. The FDA determined that trial participants experienced enough improvement and faced a low-enough risk for the treatments to be approved.

Chorea is relatively easy to measure because it’s a visible symptom that gets worse over time. The dilemma is how to test medication effectiveness in patients who don’t yet have symptoms. I believe that most people don’t want to wait until they have HD symptoms to begin treatment; they’d prefer to take a medicine to prevent symptoms from ever manifesting.

Because we can’t measure symptoms like chorea in patients without those symptoms, we have to look inside the body. The scientific community has identified several biomarkers that may help to measure HD progression, but none have been approved for use in clinical trials. Because of this, there is very little opportunity for pre-symptomatic individuals to enroll.

Running a clinical trial is expensive, so it makes sense to enroll patients whose progress could be easily identified and measured. But this also means that we simply don’t know if any of the treatments in trials would help pre-symptomatic individuals.

So my fellow advocates and I are asking our community: If you’re pre-symptomatic and gene-positive for HD, would you want to join a clinical trial to see if a treatment might work for you? What risks would you be willing to take, and what benefits would you hope to see?

We hope to gain a better understanding of this issue through an HD community survey that will be available throughout June. This isn’t an easy, multiple-choice questionnaire; it will require some deep thought.

I don’t believe this question has ever been asked in the HD community. Though it’s an uncomfortable topic, the answers will provide us with valuable data to bring to the FDA, helping the agency to better understand this population’s wishes and concerns.

Please keep an eye out for our HD community survey in June. The more people who take the time to fill it out, the more impactful the results will be.

Note: Huntington’s Disease News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Huntington’s Disease News or its parent company, BioNews, and are intended to spark discussion about issues pertaining to Huntington’s disease.