Daiichi Sankyo's Pexidartinib Under Regulatory Review in US and EU for Tenosynovial Giant Cell Tumor
Apr 08, 2019 14:01
CST Updated
14:01
Daiichi-Sankyo
Pharmaceutical R&D Developer
European Medicines Agency
The European Medicines Agency (EMA) is a decentralized agency of the European Union (EU), located in London. It began operations in 1995. The agency is responsible for the scientific evaluation, supervision, and safety monitoring of medicines developed by pharmaceutical companies for use in the EU. By ensuring that all medicines available on the EU market are safe, effective, and of high quality, the EMA protects public and animal health in the 28 EU Member States and countries of the European Economic Area.
April 08, 2019 /Bio ValleyBIOON/ -- Japanese pharmaceutical company Daiichi Sankyo recently announced that the European Medicines Agency (EMA) has accepted the Marketing Authorization Application (MAA) for pexidartinib. The MAA seeks approval for pexidartinib for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) who have severe morbidity or functional limitations and are not candidates for surgery to improve their condition. Previously, the EMA had granted orphan drug designation to pexidartinib for the treatment of TGCT.
In the United States, the FDA accepted the New Drug Application (NDA) for pexidartinib in the treatment of TGCT in February 2019 and granted it Priority Review designation (PRD), with a Prescription Drug User Fee Act (PDUFA) target date of August 3, 2019. Previously,FDAPexidartinib has also been granted Breakthrough Therapy designation and Orphan Drug designation for the treatment of TGCT.
Pexidartinib is an investigational, novel oral small molecule that effectively inhibits the colony-stimulating factor-1 receptor (CSF1R). CSF1R is the primary growth driver of abnormal cells in the synovium associated with tenosynovial giant cell tumor (TGCT). Pexidartinib also inhibits c-kit and FLT3-ITD.
Currently, there is no systemic therapy for TGCT. If approved, pexidartinib will become the first and only drug approved for the treatment of symptomatic TGCT associated with severe morbidity or functional limitations and not amenable to improvement with surgery.
January 31, 2019, U.S. ClinicalTumorThe American Society of Clinical Oncology (ASCO) designated “Advances in the Treatment of Rare Cancers” as the “Advance of the Year,” selecting pexidartinib as one of the top five advances in the treatment of rare diseases, hailing it as the first promising experimental therapy for tenosynovial giant cell tumor (TGCT).
Molecular structure of pexidartinib (Image source: apexbio.cn)
The submission of the New Drug Application (NDA) and Marketing Authorization Application (MAA) for pexidartinib was based on data from the pivotal Phase III clinical study, ENLIVEN. This was the first placebo-controlled study to evaluate a systemic investigational therapy in patients with tenosynovial giant cell tumor (TGCT). Results from this study were presented at the 2018 American Society of Clinical OncologyTumorpresented at the American Society of Clinical Oncology (ASCO) Annual Meeting. The data showed that, assessed by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), the overall response rate (ORR) was 39% in the oral pexidartinib group versus 0% in the placebo group at Week 25 of treatment, with a statistically significant difference (p < 0.0001), thereby meeting the primary endpoint of the study. Among patients who achieved a response in the pexidartinib group, no disease progression was observed after a median follow-up of 6 months (maximum 17 months).
Tenosynovial Giant Cell Tumor (TGCT), also known as Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCT-TS), is a rare, typically benign tumor of the joint or tendon sheath that may exhibit local invasiveness in some patients. TGCT affects synovial joints, bursae, and tendon sheaths, leading to swelling, pain, stiffness, and reduced mobility in the affected joint or limb. Patients are typically diagnosed between the ages of 20 and 50, depending on the TGCT subtype, with women beingTumortwice that of males.
TGCT is classified into two types: localized (90%) and diffuse (10%). The recurrence rate of localized TGCT after complete resection is approximately 15%, while that of diffuse TGCT is around 20-50%. Currently, the primary treatment for TGCT includes surgical tumor resection. However, for recurrent, difficult-to-treat, orTumorFor patients with diffuse-type tenosynovial giant cell tumor (TGCT) involving the bones, tendons, ligaments, and other joint structures, surgical resection is more challenging or may fail to yield improvement. In more severe cases, additional surgery may lead to serious joint damage, debilitating functional impairment, reduced quality of life, and amputation. (Bioon.com)