Abbisko Therapeutics Co. Ltd.’s colony-stimulating factor 1 receptor (CSF-1R) inhibitor, pimicotinib, met both primary and secondary endpoints in the phase III Maneuver global study evaluating pimicotinib for treatment of tenosynovial giant cell tumor (TGCT).

Based on the data, Abbisko will file an NDA in China on behalf of Darmstadt, Germany-based Merck KGaA, which holds China commercialization rights to pimicotinib, Abbisko founder and CEO Yao-Chang Xu told BioWorld.

As previously reported by BioWorld, Abbisko out-licensed China rights to pimicotinib to Merck in December 2023 in a deal worth up to $605.5 million. Merck has an exclusive license to commercialize products comprising pimicotinib (ABSK-021) for all indications in mainland China, Hong Kong, Macau and Taiwan. Merck also has the option to commercialize the drug globally for an additional fee.

“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,” Xu said.

The phase III results show that at week 25, pimicotinib achieved an objective response rate (ORR) of 54% compared to 3.2% for the placebo group (p< 0.0001) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

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 who have not received prior anti-CSF1/CSF1R therapy. The study is being conducted in China (n=45), Europe (n=28) and North America (n=21). In the double-blind first part of the trial, 94 patients were randomized 2-to-1 to receive either a 50-mg daily dose of pimicotinib (n=63) or placebo (n=31) for 24 weeks. The primary endpoint is ORR at week 25 as measured by RECIST v1.1. 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.

Statistically significant and clinically meaningful improvements were also seen in all key secondary endpoints, including pain and stiffness. For stiffness, patients on the study drug saw a -3% mean change from baseline vs. -0.57% for placebo (p<0.0001) as measured by the NRS scale. And in pain, patients on pimicotinib saw a 2.32% mean change from baseline vs. 0.23% in the placebo group (p<0.0001) using the BPI scale.

Pimicotinib’s safety profile was consistent with prior 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.

First CSF-1R inhibitor developed in China to enter global trials

Internally discovered and developed by Abbisko, pimicotinib is an orally bioavailable, selective, small molecule and is the first CSF-1R inhibitor developed in China to enter global phase III trials. Registrational trials led by Chinese pharmaceutical companies and launched simultaneously worldwide are rare, Abbisko Chief Medical Officer Jing Ji told BioWorld in an earlier interview.

“Our data is clear that our molecule is best in class,” Xu said. Pimocotinib is Abbisko’s first molecule, and the goal was always to aim for best in class and first in class, he said.

“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 responses across different populations,” Xu said.

Also known as pigmented villonodular synovitis, TGCT is a locally aggressive neoplasm that affects synovial joints, mucous sacs and tendon membranes, resulting in swelling, pain, stiffness and decreased activity of the affected joints.

The World Health Organization classifies TGCT as either localized or diffuse, with localized TGCT cases accounting for 80% to 90% of cases, and diffuse TGCT accounting for 10% to 20% of cases. Overexpression of CSF1 occurs in most TGCTs.

Surgical resection is the standard treatment for TGCT; however, not all patients are suitable for surgical treatment as it is difficult to remove tumors in diffuse patients by surgery and could lead to severe joint damage, total synovectomy, joint replacement or even amputation, and the risk of surgical complications can be high.

Currently, there are no highly selective CSF-1R inhibitors approved in China, and for those TGCT patients not able to have surgery, there is no approved drug available in China.

The only drug approved to treat TGCT, Turalio (pexidartinib, Daiichi Sankyo Co. Ltd.) won U.S. FDA clearance in 2019 for adults with symptomatic TGCT associated with severe morbidity or functional limitations and not responsive to improvement with surgery. Prescribing information for Turalio includes a boxed warning about the risk of serious and potentially fatal liver injury, and the FDA requires a risk evaluation and mitigation strategy (REMS) program.

In comparison, Abbisko’s pimicotinib is much safer, Xu said.

In late January, the U.S. FDA granted breakthrough therapy designation to pimicotinib for patients with TGCT who are not able to have surgery. China’s NMPA designated pimicotinib as a breakthrough therapy in July 2022.

In addition to TGCT, Abbisko is exploring the potential of pimicotinib in treating other indications, including solid tumors, and it has obtained approval from the NMPA to conduct a phase II trial in chronic graft-vs.-host disease (cGVHD).

Abbisko has built an extensive pipeline of 16 innovative small-molecule programs focused on precision oncology and immuno-oncology.

Next in line is FGFR4 inhibitor irpagratinib (ABSK-011) for liver cancer, which will be Abbisko’s top priority for 2025, Xu said, noting that the company reported positive phase II data in September.

“The data look very good. This molecule is first in class, and we did have some competitors, but they have dropped out,” he said. The company is in discussions with the FDA and China’s NMPA to begin registrational trials by the end of this year or early next year.

Liver cancer remains a huge problem in China. Nearly 1 million patients are diagnosed with liver cancer globally every year, and roughly half of those are in China.

Abbisko’s stock on the Hong Kong Stock Exchange (HKSE:2256) dropped 7.37% on the news, closing at from HK$4.70 (US60 cents) at close of trading Nov. 12.

By Tamra Sami

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