Merck KGaA's pimicotinib, a CSF-1R inhibitor, has met its primary endpoint in the Phase 3 MANEUVER trial for the treatment of tenosynovial giant cell tumor (TGCT). The study demonstrated a statistically significant and clinically meaningful improvement in objective response rate (ORR) compared to placebo, positioning pimicotinib as a potential competitor in the TGCT therapy market.
The MANEUVER trial, a randomized, double-blind, placebo-controlled study, evaluated the efficacy and safety of pimicotinib in patients with TGCT. The primary endpoint, ORR at week 25, was achieved by 54% of patients treated with pimicotinib compared to 3.2% in the placebo group. This significant difference highlights the potential of pimicotinib as a targeted therapy for this rare and debilitating condition.
Clinical Efficacy and Secondary Endpoints
In addition to the primary endpoint, pimicotinib also demonstrated efficacy on key secondary endpoints. Patients treated with pimicotinib experienced a three-point reduction in joint stiffness based on the NRS measure, compared to a 0.57-point reduction in the placebo group. Furthermore, the BPI pain score showed a 2.32-point reduction with pimicotinib compared to a 0.23-point reduction with placebo. These results indicate that pimicotinib can provide meaningful improvements in both joint stiffness and pain, which are critical symptoms affecting the quality of life for TGCT patients.
Competitive Landscape
If approved, pimicotinib will compete with existing therapies such as Daiichi Sankyo's Turalio (pexidartinib), a CSF1R, KIT, and FLT3 inhibitor, and potentially Ono Pharma's CSF-1R inhibitor vimseltinib. Turalio, approved by the FDA in 2019, achieved an ORR of 38% in its pivotal ENLIVEN study, while pimicotinib demonstrated a 54% ORR in the MANEUVER trial. However, cross-trial comparisons should be made with caution due to differences in study designs and patient populations.
About TGCT
TGCT is a rare, non-malignant tumor that affects the joints and tendons. It is caused by the overproduction of the protein CSF-1, which leads to inflammation, proliferation of cells, and destruction of the joint matrix. This results in joint pain, swelling, stiffness, and limited range of motion, significantly impacting patients' daily lives. TGCT affects approximately 11 people per million worldwide.
Future Directions
Abbisko Therapeutics will collaborate with Merck on the registration of pimicotinib as the first systemic therapy for TGCT in China. The MANEUVER trial included both Asian and Western patients, supporting the potential for global registration and access to this novel therapy.
