20 July 2022, Shanghai – Abbisko Therapeutics Co., Ltd. (“Abbisko Therapeutics” hereafter) today announced that its CSF-1R inhibitor ABSK021 had been granted the breakthrough therapy designation from Center for Drug Evaluation, NMPA for the treatment of tenosynovial giant cell tumor (TGCT) that not amenable to surgery.

The Breakthrough Therapy Designation is a CDE program^[1] for innovations during clinical trials that are used for the prevention and treatment of serious life-threatening diseases or seriously affect the quality of life, and there are no effective prevention and treatment methods or there is sufficient evidence to show that they have obvious clinical advantages compared with existing treatment methods.

This breakthrough therapy designation approval is based on results from the phase Ib clinical trial of TGCT cohort in China for CSF-1R inhibitor ABSK021.

TGCT, also known as pigmented villonodular synovitis, 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 which seriously affect the patient's quality of life^[2]. 

According to the 2013 World Health Organization classification, TGCTs were classified as localized TGCT and diffuse TGCT. Compared with localized TGCT (80%-90%), the incidence rate of diffuse TGCT is lower (10-20%)^[3,4]. 

Overexpression of colony-stimulating factor 1(CSF1) occurs in most TGCTs. Surgical resection is the standard treatment for TGCT. However, not all patients are suitable for surgical treatment. It is difficult to remove tumors of diffuse patients by surgery, which may possibly lead to severe joint damage, total synovectomy, joint replacement, or even amputation, and the risk of surgical complications can be high. It has been reported that more than 50% of patients with diffuse TGCT will undergo recurrence after surgical resection^[5]. For those TGCT patients not amenable to surgery, there is currently no approved drug available in China.

ABSK021 is a novel, orally available, highly selective, and highly potent small molecule inhibitor of CSF-1R, independently developed by Abbisko Therapeutics. It is also the first selective CSF-1R inhibitor discovered by a Chinese company that has advanced into human clinical trial. A number of studies have shown that blocking the CSF-1R signaling pathway could effectively modulate and change macrophage functions, and potentially treat many macrophage-dependent human diseases. Abbisko has completed a phase Ia dose escalation study for ABSK021 in the U.S., with phase Ib expansion ongoing in both U.S. and China. In addition to TGCT, Abbisko is actively exploring the potential of ABSK021 in treating other indications including many types of solid tumors in clinic, and has collaborated with Sperogenix in exploring its potential for treating ALS and other CNS diseases. As of the date of this press release, no high-selective CSF-1R inhibitor has been approved in China.

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[1]https://www.nmpa.gov.cn/zhuanti/ypzhcglbf/ypzhcglbfzhcwj/20200708151701834.html

[2] Vaynrub A, Healey JH, Tap W, Vaynrub M. Pexidartinib in the Management of Advanced Tenosynovial Giant Cell Tumor: Focus on Patient Selection and Special Considerations. Onco Targets Ther. 2022;15:53-66.

[3] Mastboom MJL, Verspoor FGM, Verschoor AJ, et al. Higher incidence rates than previously known in tenosynovial giant cell tumors. Acta Orthop. 2017; 88(6):688–94.

[4] de Saint Aubain Somerhausen N, van de Rijn M: Tenosynovial giant cell tumour, diffuse type, in Fletcher CDM, Bridge JA, Hogendoorn P, Mertens F, eds: WHO Classification of Tumours of Soft Tissue and Bone, ed 4: International Agency for Research on Cancer (IARC), 2013, vol 5, pp 102-103.

[5] Verspoor FG, van der Geest IC, Vegt E, Veth RP, van der Graaf WT, Schreuder HW. Pigmented villonodular synovitis: current concepts about diagnosis and management. Future Oncol. 2013;9(10):1515-1531.