Merck KGaA recently shared positive results from its Phase III MANEUVER trial on pimicotinib, an investigational oral therapy for tenosynovial giant cell tumor (TGCT).
TGCT is a rare, aggressive joint condition caused by overactive colony-stimulating factor 1 (CSF-1). A generally non-cancerous growth that forms in the tissue lining the joints, tendons or fluid-filled sacs around joints, TGCT often leads to abnormal joint tissue growth, painful swelling and stiffness.
Primarily affecting young and middle-aged adults who can work, TGCT often limits daily activities due to its impact on mobility and joint health. Currently, surgery is the main treatment, but frequent recurrences make systemic therapy highly desirable for long-term management.
Pimicotinib, developed by Abbisko Therapeutics, acts as a selective small-molecule inhibitor of the CSF-1 receptor (CSF-1R), aiming to reduce the overgrowth of tissues in TGCT. In MANEUVER, pimicotinib significantly reduced tumor burden compared to placebo.
At 25 weeks, the objective response rate (ORR) reached 54 percent in the pimicotinib group, compared to 3.2 percent for placebo (p < 0.0001). This substantial difference demonstrates pimicotinib’s potential as a reliable alternative to surgery for TGCT, particularly where surgical relief proves short-lived.
Secondary outcomes showed a positive impact on patients’ quality of life, especially in reducing joint stiffness and pain. On the Numeric Rating Scale (NRS), pimicotinib patients saw a stiffness improvement of three points, compared to 0.57 for placebo.
Pain scores, measured by the Brief Pain Inventory (BPI), showed an average reduction of 2.32 points with pimicotinib, far surpassing the 0.23 point change seen with placebo (p < 0.0001). These findings align with early trial results, reinforcing pimicotinib’s promise for improving daily function in TGCT patients.
Pimicotinib also showed a favorable safety profile, with adverse event-related discontinuations in only 1.6 percent of patients. This low rate highlights its potential as a viable long-term option, especially given TGCT’s chronic, recurring nature.
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Yaochang Xu, chairman and CEO of Abbisko Therapeutics, emphasized the MANEUVER study’s inclusion of both Asian and Western patients. This design provides insights into TGCT’s progression across diverse populations, supporting a universally effective treatment approach.
With these successful Phase III results, Merck KGaA and Abbisko now plan to seek regulatory approval in China and expand pimicotinib’s reach globally, positioning it as a breakthrough therapy in TGCT care.
As of today, Turalio (pexidartinib) remains the only US Food and Drug Administration (FDA)-approved oral therapy for TGCT. Approved in 2019, Turalio targets CSF-1R to reduce tumor size and alleviate symptoms in patients for whom surgery is not an option.
Another promising treatment, vimseltinib, is currently under Priority Review by the FDA, with a decision expected by February 17, 2025. In the Phase III MOTION study, when compared to placebo, vimseltinib achieved significant tumor reduction and symptom relief in TGCT patients not suitable for surgery.
If approved, pimicotinib could potentially follow these treatments as a third oral option, broadening the landscape of non-surgical TGCT therapies.
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