HDSA 2026: New oral therapy headed for pivotal Huntington’s trial
SOM3355 may ease chorea, other symptoms without common side effects
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SOM Biotech is preparing to launch a global late-stage clinical trial to evaluate whether SOM3355, its experimental oral therapy, can safely and effectively ease movement problems and other symptoms in people with Huntington’s disease.
If positive, data from the upcoming Phase 3 trial, which is expected to start early next year, will be used to support an application seeking the therapy’s approval in the U.S. — a path agreed to by the U.S. Food and Drug Administration (FDA) in a meeting last year.
FDA clears path for pivotal study
“I’m really happy to say that we have the green light from the FDA … for a single … study to get to approval,” Silvia Panigone, PhD, SOM Biotech’s CEO, said in a talk during the 41st Huntington’s Disease Society of America (HDSA) annual convention, which was held last week in Arizona. The talk was titled “SOM335 – A New Different Molecule to Treat The Symptoms of Huntington’s Disease.”
The decision to move to late-stage clinical testing is based on positive Phase 2 trial findings showing that SOM3355 eased chorea, or uncontrollable jerky movements, to a degree Panigone described as similar to some currently approved therapies, but without many of the associated side effects. Notably, the therapy also appeared to ease anxiety and depression.
“We have shown a proven benefit on chorea similar to the other drugs, [and] … a preliminary benefit on depression and anxiety, which really makes this drug different and with important potentiality,” Panigone said.
Huntington’s is a genetic disorder that causes damage to the brain. Chorea, or involuntary, dance-like movements, is a hallmark symptom of the disease, but other motor problems, as well as cognitive, behavioral, and mental health symptoms, are also common.
SOM is a company focused on repurposing molecules that have well-established safety profiles and may have potential for treating new symptoms or conditions, whether or not they have reached the market. Repurposing existing molecules can shorten a treatment’s development process and lower its cost, because the compound’s safety is already established.
SOM3355 is a formulation of bevantolol hydrochloride, a medication that’s been used for decades outside the U.S. as a mild antihypertensive, or blood pressure-lowering medication.
Therapy targets chorea differently
The therapy was found to be a suppressor of VMAT2, a protein that is targeted by all treatments currently approved for Huntington’s-related chorea: Xenazine (tetrabenazine), its derivative Austedo (deutetrabenazine), and Ingrezza (valbenazine). However, it is thought to work differently than these treatments.
Importantly, bevantolol hydrochloride had no known associated risk of depression or suicidal thoughts — which are known side effects of all three chorea medications.
Based on these findings, SOM is exploring SOM3355 as a potential treatment for chorea associated with Huntington’s. The experimental therapy received U.S. orphan drug designation for that indication, a status meant to help speed its clinical development and regulatory review.
After a proof-of-concept Phase 2a clinical trial (NCT03575676) in Spain, launched in 2018, yielded positive results supporting SOM3355 as a potential chorea treatment, SOM launched a larger Phase 2b study (NCT05475483) to further test the therapy.
The Europe-based Phase 2b trial enrolled 139 adults with Huntington’s-related chorea who were randomly assigned to take one oral capsule of SOM3355 at one of two doses, either 200 or 300 mg, or a placebo, twice daily for about three months.
The main goal was to see if SOM3355 would ease chorea, as measured with a standardized test called the Total Maximal Chorea (TMC) score, in participants who were not taking antipsychotic medications.
Highest dose showed chorea benefits
According to Panigone, the highest tested dose, 300 mg twice daily, showed “a consistent reduction in the TMC score” in this subgroup of patients. SOM3355’s impact on chorea was comparable to what’s typically seen with certain chorea treatments, she said.
SOM3355 also showed improvements in total motor score, and Panigone said clinical and patient global impression measures also improved, with the patient-rated measure showing statistical improvement.
Although the Phase 2b trial was not designed to assess the therapy’s impact on symptoms other than chorea, Panigone said SOM3355 also appeared to have “a beneficial effect” on mental health symptoms such as anxiety and depression.
Safety data indicated that SOM3355 did not lead to sleepiness, fatigue, parkinsonism, restlessness, or an increased risk of suicidal thoughts or behaviors — all of which are common side effects of chorea treatments.
While SOM3355 was associated with reductions in blood pressure, values generally remained within normal ranges, Panigone emphasized.
Global trial planned for next year
The upcoming Phase 3 trial, whose preliminary design was agreed to by the FDA, is expected to recruit about 140 people with mild to severe Huntington’s symptoms across the U.S. and Europe. Half will receive 300 mg of SOM3355 twice daily, while the other half will receive a placebo, for about three months.
The study aims to evaluate the therapy’s safety and ability to ease chorea, as well as other Huntington’s symptoms. Those completing the trial will have the option to enter an open-label extension study, where all will be treated with SOM3355 and monitored for longer-term outcomes.
Note: The Huntington’s Disease News team is providing virtual coverage of the Huntington’s Disease Society of America’s annual conference June 25-27. Go here to see the latest stories from the conference.
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