Second Drug for Benign Synovial Tumor Condition Wins FDA Approval

The FDA approved the small-molecule inhibitor vimseltinib (Romvimza) for adults with symptomatic tenosynovial giant cell tumor (TGCT), a rare, non-malignant, but debilitating, condition arising in the synovium, the agency announced Friday.

The approval stipulates use in adults with symptomatic TGCT for whom surgery could worsen functional limitation or cause severe morbidity. The condition has an estimated worldwide incidence of 43 cases per 1 million population, including localized (more common) and diffuse forms of the disease.

TGCT arises from dysregulation of CSF1, leading to overproduction of the CSF1 protein and accumulation in the synovial covering of joint spaces and in tendon sheaths. Affected patients have significant swelling, pain, and joint stiffness.

Standard treatment is surgical resection, which often is curative for localized disease, but no consensus exists for the optimal technique. Pexidartinib (Turalio) was the only FDA-approved drug treatment, which carries a significant risk of side effects that include cholestatic hepatotoxicity, liver injury, and hair/skin hypopigmentation.

Support for the approval came from the phase III MOTION trial involving 123 patients who were not good candidates for surgery. Patients were randomized 2:1 to vimseltinib or placebo for 24 weeks, followed by an open-label period during which patients on vimseltinib could continue the drug and patients in the placebo group could cross over to active therapy.

The primary endpoint was overall response rate (ORR) by blinded independent radiologic review at week 25. The results showed an ORR of 40% with vimseltinib versus 0% in the placebo group (P<0.0001). Median duration of response (DOR) with vimseltinib was not reached, and 85% of responding patients had a DOR ≥6 months, including 19 (58%) patients with a DOR ≥9 months. Patients in the vimseltinib arm also had significant improvements in range of motion, physical functioning, and pain as compared with the placebo group.

The most common adverse events (≥20% of patients) with vimseltinib include increased liver enzymes, periorbital edema, fatigue, rash, increased cholesterol, peripheral edema, facial edema, decreased neutrophils, decreased leukocytes, and pruritus.

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