FDA Grants Orphan Drug Status to SOM Biotech’s Chorea Therapy

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by Patricia Inacio PhD |

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The U.S. Food and Drug Administration (FDA) has granted an orphan drug designation to SOM3355, an investigational treatment for chorea, or involuntary jerky movements, associated with Huntington’s disease, its developer SOM Biotech has announced.

Orphan drug status helps to encourage the development of therapies for rare and serious diseases, through 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 Huntington’s patients and usually occurs during the early intermediate stage of the disease, several years after disease onset. It is characterized by brief and abrupt movements that are irregular and unpredictable, and can interfere with swallowing, speech, posture, and walking.

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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 severe side effects including sedation, drowsiness, parkinsonism, and a risk of depression.

SOM3355, or bevantolol hydrochloride, is a therapy commonly used to treat hypertension. Using SOM Biotech’s proprietary artificial intelligence-based computational technology, the company 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 molecule’s chemical structure differs considerably from its reference compound and as such is less likely to result in the side effects seen with Xenazine.

“SOM3355’s profile is a compelling alternative to existing drugs in this space and we are excited by the added momentum that Orphan Drug Designation gives to the project to ensure we can make this treatment available as soon as possible to patients,” said Raúl Insa, MD, PhD, founder and CEO of SOM Biotech.

A recently completed proof-of-concept Phase 2a trial study (NCT03575676) met its primary endpoint, with more than half (57.1%) of SOM3355-treated patients showing a lessening of their chorea when compared to patients given a placebo, according to another company press release.

Chorea was assessed using the total maximal chorea score of the Unified Huntington’s Disease Rating Scale. 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% by four points; 17.9% by five points; and 10.7% by six points.

SOM3355 was well-tolerated with mild or moderate adverse events, most commonly headache, fatigue, nausea, and vomiting.

In the trial, a total of 32 Huntington’s patients with chorea were randomly assigned into two groups by treatment schedule. One group received a placebo twice daily 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 a day with 100 mg of SOM3355 for six weeks, 200 mg for six weeks, 100 mg for six weeks, and then a placebo for the final six weeks.

“There is a huge unmet medical need for new treatment options to treat symptoms of [Huntington’s disease], including chorea, and we are very encouraged by the results we have seen thus far,” Insa said.

A Phase 2b trial is expected to start later this year.