An Ono Pharma drug for a type of tumor affecting tissues of the joints is now FDA approved, giving the Japanese company a product with dosing and safety advantages over the Daiichi Sankyo product that was the first systemic therapy for this rare condition.
The approval of the Ono drug, vimseltinib, covers the treatment of adults whose tenosynovial giant cell tumor (TGCT) cannot be surgically removed. The twice-weekly capsule will be marketed under the brand name Romvimza.
TGCT stems from a genetic abnormality that results in overexpression of a protein called colony-stimulating factor receptor. This protein recruits other tumor-promoting cells, leading to the growth of tumors in and around joints. While these tumors are not malignant, they damage surrounding tissues and cause pain and swelling. These tumors also limit movement of the joint. Surgery is the standard treatment, but these tumors can come back and for some patients, surgery can lead to more complications.
Romvimza inhibits CSF-1. The small molecule was initially developed by Waltham, Massachusetts-based Deciphera Pharmaceuticals, whose drugs are based on a technology that targets a region of an enzyme that activates it or inactivates it like an on-off switch. Last year, Ono acquired Deciphera in a $2.4 billion deal. In addition to Romvimza, Ono gained Qinlock, a cancer drug that Deciphera steered to a 2020 FDA approval in gastrointestinal stromal tumor.
Inhibiting CSF-1 to treat TGCT was validated by Turalio, a twice-daily Daiichi Sankyo drug that won its FDA approval in this indication in 2019. But Turalio’s label carries a black box warning for the risk of liver toxicity. This complication was observed in some patients treated with the drug in clinical trials; there was one fatality. Daiichi Sankyo must provide a Risk Evaluation and Mitigation Strategy, a plan that informs clinicians and patients about the safety risks. In 2020, European regulators refused marketing authorization for Turalio.
Clinical tests of Ono’s Romvimza showed no reports of liver toxicity. But due to the serious liver injury observed in Daichii’s CSF-1 inhibitor, Romvimza’s label advises avoiding use of the drug by patients who already have high levels of liver enzymes in the blood. The FDA also recommends liver tests before and during treatment with Romvinmza.
In its 123-patient Phase 3 study, twice-weekly Romvimza led to a 40% overall response rate measured at week 25 compared to 0% in the placebo arm. Results also showed statistically significant improvement in active range of motion as well as patient reported measures of physical functioning and pain. Romvimza is still under regulatory review in Europe.
“The MOTION Phase 3 study demonstrated ROMVIMZA’s ability to shrink tumors along with being the first well-tolerated agent to demonstrate significant improvement in a number of other important quality-of-life measures without any observed liver injury as seen with other approved TGCT treatment,” Dr. Hans Gelderblom, chair of the department of medical oncology at Leiden University Medical Center, said in Ono’s approval announcement. “Romvimza is a differentiated treatment that has the potential to address the significant unmet needs of the TGCT community.”
There are other companies vying to treat TGCT. Merck KGaA could compete with pimicotinib, a CSF-1 inhibiting small molecule being developed under a commercialization agreement with Abbisko Therapeutics. Last November, the two companies announced this drug met the main goal of its pivotal study. Meanwhile, SynOx Therapeutics has reached Phase 3 testing with emactuzumab, an antibody designed to block the CSF-1 receptor. Last year, the privately held company raised $75 million in Series B financing for the pivotal test of this molecule.
Photo: Getty Images, Sarah Silbiger
