Pimicotinib Significantly

Pimicotinib Significantly Improved Outcomes for Patients with Tenosynovial Giant Cell Tumor in a Global Phase III Trial

• Phase III MANEUVER study met      primary endpoint, with an objective response rate at week 25 of 54.0% for      pimicotinib versus 3.2% for placebo (p<0.0001)

• Statistically significant and      clinically meaningful improvements also seen in all key secondary      endpoints, including pain and stiffness

• Oral, once-daily treatment      with pimicotinib was well-tolerated, with very low rates of      discontinuation due to treatment-related adverse events

• Pimicotinib is being      developed by Abbisko Therapeutics Co., Ltd.; Merck holds commercial      license for pimicotinib in Chinese mainland, Hong Kong, Macau, and Taiwan,      with option for rest of world

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DARMSTADT, Germany -- (BUSINESS WIRE) --

Merck, a leading science and technology company, today announced that the Phase III MANEUVER trial of pimicotinib, an investigational medicine being developed by Abbisko Therapeutics Co., Ltd., met its primary endpoint, demonstrating significant improvement in objective response rate (ORR) in patients with tenosynovial giant cell tumor (TGCT). The ORR for pimicotinib at week 25 was 54.0% compared with 3.2% for placebo (p<0.0001).

Notably, the study also showed that treatment with pimicotinib provided statistically significant and clinically meaningful improvements in secondary endpoints associated with important patient outcomes in TGCT, including stiffness by Numeric Rating Scale (NRS; -3.00 mean change from baseline vs. -0.57 for placebo, p<0.0001) and pain by Brief Pain Inventory (BPI; -2.32 vs. 0.23 mean change from baseline, p<0.0001). Further efficacy and safety data from the MANEUVER study will be presented at an upcoming medical conference.

“TGCT tends to be a disease of the young. This rare, benign tumor that grows in and around the joints primarily affects young and middle-aged adults in their working years. The swelling, pain, stiffness and limited mobility caused by the disease can have a significant impact on the ability to perform daily activities, limiting patients’ work and social lives. Treatment often involves surgery, yet the high recurrence rate and potential complications from repeated surgical interventions can be very challenging for patients to deal with, creating an urgent need for systemic therapy that could control tumor growth,” said Professor Niu Xiaohui, Director of the Bone and Soft Tissue Tumour Diagnosis and Research Centre at Beijing Jishuitan Hospital. “Based on these new data from the MANEUVER study, together with once-daily oral administration that may promote long-term adherence and pimicotinib’s selective inhibition of CSF-1R, this investigational medicine has the potential to establish a new treatment paradigm for patients with TGCT.”

In MANEUVER, pimicotinib was well-tolerated, and the safety profile was consistent with previously reported data, with no evidence of cholestatic hepatotoxicity. Treatment-emergent adverse events (TEAEs) leading to treatment discontinuation occurred in 1.6% (n=1) of patients treated with pimicotinib; TEAEs leading to dose reduction occurred in 7.9% (n=5) of pimicotinib-treated patients.

“There is a tremendous unmet need for effective, well-tolerated systemic treatment for TGCT, a disease primarily caused by CSF-1 overexpression that leads to joint tissue thickening and overgrowth, severely impacting patients’ lives. These Phase III data from MANEUVER confirm results of Abbisko’s Phase I study, indicating that targeting CSF-1R with pimicotinib has the potential to offer a new treatment option for patients. As we work with Abbisko to review the data from this study and prepare to share it with regulators in China, we are focused on our shared goal of bringing pimicotinib to patients in need,” said Danny Bar-Zohar, Global Head of Research & Development and Chief Medical Officer for the Healthcare business sector of Merck.

“As the first global trial to enroll both Asian and Western patients with TGCT in balanced proportions across multiple regions, MANEUVER is a landmark global study that allows for detailed outcome comparisons. This can facilitate a deeper understanding of disease characteristics and potential similar response across different populations,” said Yaochang Xu, Chairman and CEO of Abbisko Therapeutics. “This unique study shows that pimicotinib has the potential to provide a novel oral small molecule therapy option for TGCT patients, representing a key advancement within the emerging class of CSF-1R inhibitors. We look forward to collaborating with Merck as we pursue registration of pimicotinib as the first therapy option indicated for the systemic treatment of TGCT in China.”

Pimicotinib is an investigational orally administered, highly selective and potent small-molecule inhibitor of colony stimulating factor-1 receptor (CSF-1R) being developed by Abbisko. In December 2023, Abbisko Therapeutics and Merck entered into an agreement granting an exclusive license to commercialize products comprising or containing pimicotinib for all indications in Chinese mainland, Hong Kong, Macau, and Taiwan, with an option for the rest of world including the US.

About MANEUVER

The pivotal Phase III 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 are eligible for systemic therapy and have not received prior anti-CSF-1/CSF-1R therapy. The study is being conducted 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 PROMIS.

After the double-blind Part 1, eligible patients may continue to the open-label Part 2 for up to 24 weeks of dosing. Patients who complete Part 2 may then enter the open-label extension phase (Part 3) for extended treatment and safety follow-up.

About Tenosynovial Giant Cell Tumor

Tenosynovial giant cell tumor (TGCT) is a rare, benign and locally aggressive disease that originates in the synovial lining of joints, bursae, and tendon sheaths, leading to thickening and overgrowth of these tissues. TGCT is life-limiting, causing joint pain, stiffness, swelling, and reduced range of motion, significantly impacting the 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.

Currently, surgery is the primary treatment option for TGCT. However, surgical resection is often limited by risk of post-surgical recurrence and associated morbidity. This highlights the unmet need for well-tolerated and effective systemic treatment in TGCT.

About Pimicotinib (ABSK021)

Pimicotinib (ABSK021), which is being developed by Abbisko Therapeutics, is a novel, orally administered, highly selective and potent small-molecule inhibitor of CSF-1R. Pimicotinib has been granted breakthrough therapy designation (BTD) by China National Medical Products Administration (NMPA) and the US Food and Drug Administration (FDA) and priority medicine (PRIME) designation from the European Medicines Agency (EMA) for the treatment of patients with TGCT that are not amenable to surgery.

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