Merck KGaA, Darmstadt, Germany announced that the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) officially accepted the company's application for marketing authorization of pimicotinib as a Class 1 innovative drug for adult patients with tenosynovial giant cell tumors (TGCT) requiring systemic treatment. The submission follows the granting of Priority Review to pimicotinib by the CDE in May for the treatment of patients with TGCT who require systemic therapy, which is expected to expedite the review process. Pimicotinib, a potentially best-in-class investigational colony stimulating factor-1 receptor (CSF-1R) inhibitor in development by Abbisko Therapeutics Co.
Ltd., also has been granted breakthrough therapy designation (BTD) by the NMPA. TGCT is a locally aggressive and often recurring tumor of the joints that can cause high morbidity associated with swelling, pain, stiffness, and limited mobility of the affected joints, significantly impacting daily activities and quality of life in the primarily working-age population that it affects. If left untreated or in recurrent cases, TGCT can result in irreversible damage to the bone, joint and surrounding tissues.
This highlights the need for well-tolerated and effective systemic treatments that can impact tumor growth while achieving the symptoms of the disease. The application is based on results from Part 1 of the global Phase 3 MANEUVER study, in which once-daily pimicotinib demonstrated a statistically significant improvement in the primary endpoint of objective response rate (ORR) assessed by blinded independent review committee (BIRC) compared with placebo at week 25 (54.0% vs. 3.2% for placebo; p. The pivotal Phase 3 MANEUVER study is a three-part, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of pimicotinib in patients with TGCT who requires systemic therapy and have not received prior anti-CSF-1/CSF-1R therapy.
The study is being conducted by Abbisko Theraputics in China (n=45), Europe (n=28), and the US and Canada (n=21). In the double-blind Part 1, 94 patients were randomized 2:1 to receive either 50 mg QD of pimicotinib (n=63) or placebo (n=31) for 24 weeks. The primary endpoint is objective response rate (ORR) at week 25, as measured by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by blinded independent central review in the intent-to-treat (ITT) population.
Secondary endpoints include tumor volume score, active range of motion, stiffness by Numeric Rating Scale (NRS), pain by Brief Pain Inventory (BPI), and physical function measured by Patient-Reported Outcomes Measurement Information System (PROMIS). After the double-blind Part 1, eligible patients could continue to the open-label Part 2 for up to 24 weeks of dosing, results of which are expected in mid-2025. Patients who complete Part 2 may then enter the open-label extension phase (Part 3) for extended treatment and safety follow-up.
