The U.S. Food and Drug Administration (FDA) has granted orphan drug designation to SOM3355, an investigational treatment for chorea, or involuntary jerky movements, associated with Huntington’s disease, its developer SOM Biotech announced.
Orphan drug status helps encourage the development of therapies for rare and serious diseases, with benefits for developers, such as seven years of market exclusivity and exemption from FDA application fees.
Chorea is the most common involuntary movement symptom in patients with Huntington’s disease and usually occurs in the early middle stage of the disease, several years after onset. It is characterized by short, jerky, irregular and unpredictable movements, and can interfere with swallowing, speech, posture and walking.
Currently, xenazine (tetrabenazine) is approved to treat chorea in Huntington’s disease. The therapy inhibits the VMAT2 protein, known for its essential role in motor control. However, its use is linked to serious side effects, including sedation, drowsiness, parkinsonism and a risk of depression.
SOM3355, or bevantolol hydrochloride, is a commonly used therapy to treat hypertension. Using SOM Biotech’s proprietary AI-based computational technology, the company has identified SOM3355 as a potential VMAT2-inhibiting alternative.
The treatment is thought to reduce chorea by inhibiting VMAT2 through a mechanism similar to that of tetrabenazine. However, the chemical structure of the molecule differs significantly from its reference compound and as such is less likely to cause the side effects seen with Xenazine.
“The profile of SOM3355 is a compelling alternative to existing drugs in this space and we are excited about the added momentum the orphan drug designation gives the project to ensure we can make this treatment available to patients as soon as possible,” said Raúl Insa, MD. , PhD, Founder and CEO of SOM Biotech.
A recently completed phase 2a proof-of-concept trial study (NCT03575676) met its primary endpoint, with more than half (57.1%) of patients treated with SOM3355 showing a reduction in their chorea compared to to patients who received a placebo, according to another company press release.
Chorea was assessed using the Unified Huntington’s Disease Rating Scale maximum chorea total score. This score is composed of seven items, each ranging from zero (no chorea) to four (marked/prolonged chorea).
Compared to the placebo group, more patients in the SOM3355 group showed greater improvements: 28.6% by three points; 25.0% four points; 17.9% by five points; and 10.7% from six points.
SOM3355 was well tolerated with mild to moderate adverse effects, most commonly headache, fatigue, nausea, and vomiting.
In the trial, a total of 32 patients with Huntington’s chorea were randomly divided into two groups according to the treatment schedule. One group received a placebo twice a day for six weeks, then 100 mg of SOM3355 for six weeks, 200 mg for six weeks, and again 100 mg for the final six weeks.
The other group was treated twice daily with 100 mg of SOM3355 for six weeks, 200 mg for six weeks, 100 mg for six weeks, and then placebo for the final six weeks.
“There is a huge unmet medical need for new treatment options to treat the symptoms of [Huntington’s disease], including chorea, and we are very encouraged by the results we have seen so far,” said Insa.
A phase 2b trial is expected to begin later this year.
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