SOM3355 Moves Toward Phase 3 as Both EMA and FDA Signal Support

SOM3355 is an investigational therapy aimed at managing multiple symptoms of Huntington’s disease (HD) and recently crossed two key regulatory milestones. In September, the European Medicines Agency (EMA) issued a positive opinion supporting orphan drug designation for SOM3355. Now, following a productive End-of-Phase-2 meeting in the United States, the US Food and Drug Administration (FDA) has agreed that SOM Biotech’s proposed Phase 3 study and subsequent open-label extension could form the basis of a future New Drug Application.

For the HD community, these developments underscore a growing effort to expand our therapeutic toolbox, particularly for the broad and shifting range of symptoms people experience throughout the course of the disease.

Why These Decisions Matter

HD affects movement, thinking, mood, and behaviour, and these symptoms change over time as the disease progresses. There are currently no approved disease modifying therapies which can slow or halt symptom progression. However, several medications are approved to treat certain symptoms, but often only address one aspect of HD at a time.

For example, VMAT2 inhibitors and medications designed to improve movement symptoms for people with HD. While effective for many, these drugs do not address other challenges such as irritability, anxiety, restlessness, or sleep disturbances. Because of this, people with HD often take multiple medications at once. This can increase the risk of side effects, drug-drug interactions, and can create complex treatment schedules which are difficult to stick to.

A motivator for companies like SOM Biotech is that this patchwork approach creates a need for additional therapeutic tools, including options that might simplify treatments for multiple symptoms while reducing possible side effects and the complexities of juggling multiple prescriptions.

What Do We Know About SOM3355?

SOM3355 is a drug which is thought to do lots of things at the same time. Not only is it a beta-blocker, but it can also act as both a VMAT1 and VMAT2 inhibitor. VMAT proteins help package neurotransmitter molecules like dopamine into little bubbles inside brain cells. By targeting both of these systems, drugs like SOM3355 may help influence the overactive motor circuits involved in movement symptoms of HD while potentially offering broader symptom support, like for anxiety and other mood-based symptoms.

SOM Biotech reports that SOM3355 showed positive signals in both proof-of-concept and Phase 2b trials in HD. However, details from these studies have not yet been fully published or peer-reviewed. Still, the results were encouraging enough for both the EMA and FDA to green-light the next steps.

Two Agencies, One Direction: Moving Toward Phase 3

The EMA’s decision to support orphan drug designation signals that SOM3355 may offer a “significant benefit”, a specific requirement under EU rules. This doesn’t guarantee effectiveness; it simply reflects regulators’ assessment that further study is justified.

Meanwhile, the FDA’s End-of-Phase-2 meeting confirmed agreement on the design of the pivotal Phase 3 trial. The planned study, expected to begin in late 2026, will enroll individuals with mild to severe HD. Participants will receive either 600 mg of SOM3355 daily or a placebo for 12 weeks. Afterward, they may enter a nine-month open-label extension, during which all participants are given the option to receive the drug. This extension will help gather longer-term safety data and explore whether any sustained benefits emerge over time.

Orphan drug designation from the EMA and alignment with the FDA on Phase 3 trial design do not mean SOM3355 is proven to work. But they do indicate that regulators see a rationale and path forward for continued development, and that early clinical data justify taking the next step. SOM Biotech’s leadership noted that alignment with both agencies strengthens confidence that SOM3355 is being advanced along a clear, standardized regulatory path.

How Could SOM3355 Fit Into the HD Treatment Landscape?

This update on SOM3355 represents another attempt to expand our set of tools for managing HD symptoms. For many people with HD, addressing chorea alone is not enough. Behavioural changes, sleep disturbances, mood swings, and cognitive challenges often have a larger impact on independence and well-being.

A medication capable of targeting several of these issues simultaneously, while keeping side effects manageable, would be a valuable addition. Whether SOM3355 can fulfil that role will depend on forthcoming Phase 3 data.

Additionally, as individuals can respond differently to medications, more treatments mean a greater chance of finding a good personal fit for each person with HD.

Looking Ahead

SOM3355 is still an investigational drug, and only a Phase 3 trial can determine whether it is safe and effective enough to seek approval. But the combined momentum from the EMA and FDA reflects a shared interest in expanding symptom-management options for HD, a goal long voiced by both families and clinicians.

As more investigative treatments move through the pipeline, each step forward adds to the collective momentum. And whether they ultimately succeed or fail, each candidate expands what we understand about treating HD. The decision for SOM3355 marks another step toward a future where families have more, and better, options for managing the symptoms of HD.

Summary: 

• SOM3355, a multi-target drug candidate for managing HD symptoms, received a positive orphan drug opinion from the EMA and alignment from the FDA on its Phase 3 plan. 
• Early trials showed encouraging signals, and although full data aren’t yet published, regulators agree the evidence justifies moving forward. 
• A global Phase 3 trial is slated for 2026, testing 600 mg daily vs. placebo for 12 weeks, followed by a 9-month open-label extension. 
• If successful, SOM3355 could offer broader symptom relief than current single-target treatments, potentially simplifying care for people with HD.

Learn more: 

Press release: SOM Biotech secures clear registrational path for SOM3355 in Huntington’s disease after FDA End-of-Phase 2 Meeting

Press release: SOM Biotech receives positive EMA COMP opinion on European Orphan Drug Designation for SOM3355 for treatment of Huntington’s Disease