The UK Medicines and Healthcare products Regulatory Agency (MHRA) has approved vimseltinib (Romvimza, Deciphera Pharmaceuticals) to treat Tenosynovial Giant Cell Tumors (TGCTs) in adults. The agency said vimseltinib could be used when TGCTs affect movement or where surgery is not an option.

TGCTs are rare benign mesenchymal tumors that form around joints, bursae, and tendon sheaths. They are due to recurrent genomic aberrations often involving the Colony-Stimulating Factor 1 gene (CSF1) and usually affect a single joint, most often a knee or ankle.

TGCTs can be nodular or diffuse. Nodular TGCTs have a mostly indolent course, whereas diffuse TGCTs are locally aggressive.

Nodular TGCTs usually affect smaller joints and present as a single lesion in soft tissue, near tendons or interphalangeal joints. They tend to evolve over a period of years and may occasionally erode bone or involve the overlying skin.

Diffuse TGCTs typically involve extensive and infiltrative involvement of the joint synovium and/or tendon sheath and extend into extra-articular structures. They may lead to haemarthrosis, destruction of bone and cartilage, and severe disability with substantial morbidity. They frequently relapse despite treatment, including surgical resection.

Current treatment modes with active surveillance or surgical resection—marginal excision in nodular or extensive synovectomy for diffuse TGCTs—are acknowledged to be eclectic and frequently suboptimal. Joint replacement may be effective for pain but carries a high local recurrence rate.

Globally, the 5-year recurrence-free survival is 70 percent to 90 percent for nodular TGCTs and 30 percent to 80 percent for diffuse TGCTs. Very rarely, TGCTs may undergo sarcomatous transformation with metastatic spread.

Vimseltinib is an oral, selective switch-control kinase CSF1R inhibitor that slows the growth of TGCTs by blocking the tumor growth-promoting proteins.

Julian Beach, Executive Director, MHRA, Healthcare Quality and Access, said that the approval “provides a new treatment option for patients with TGCT who have symptoms but are unsuitable for surgery.”

Vimseltinib was designated an orphan medicine during development, and MHRA approval was via the International Recognition Procedure Route B.

In the phase 3 MOTION study published in The Lancet in 2024, 40 percent of the 83 patients who received vimseltinib had an objective response, with tumor shrinkage of 30 percent or more, compared with none of the 40 patients who rceived placebo.

The drug is available as hard capsules in doses of 14 mg, 20 mg, and 30 mg. The capsules should be swallowed whole with water, with or without food, twice weekly. The recommended starting dose is 30 mg, taken twice weekly at least 72 hours apart, for as long as benefit is observed or until unacceptable toxicity occurs. If so, dose interruptions or reductions may be required. Dose reductions may also be considered based on clinical improvement.