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Daiichi Sankyo’s Pexidartinib Receives Negative CHMP Opinion for Tenosynovial Giant Cell Tumor Despite FDA Approval

Jun 29, 2020 15:02 CST Updated 01:09
Daiichi-Sankyo

Pharmaceutical R&D Developer

Committee for Medicinal Products for Human Use

Committee for Medicinal Products for Human Use (CHMP)The Committee for Medicinal Products for Human Use (CHMP) is the committee within the European Medicines Agency (EMA) responsible for human medicines. The CHMP replaced the former Committee for Proprietary Medicinal Products (CPMP) in May 2004.The CHMP plays a vital role in the authorization of medicines in the European Union (EU). In the centralized procedure, the CHMP is responsible for: 1) conducting initial assessments of marketing authorization applications across the EU; assessing modifications or extensions to existing marketing authorizations (“variations”); considering recommendations from the Agency’s Pharmacovigilance Risk Assessment Committee regarding the safety of medicines on the market, and, where necessary, advising the European Commission to amend the marketing authorization of a medicinal product, or to suspend or withdraw it from the market.The CHMP also evaluates medicines authorized at the national level that are referred to the EMA, with the aim of maintaining a harmonized position throughout the EU.Furthermore, the CHMP and its working groups promote the development of medicines and pharmaceutical regulation by: providing scientific advice to companies researching and developing new medicines; developing scientific and regulatory guidelines to assist pharmaceutical companies in preparing marketing authorization applications for human medicines; and collaborating with international partners to harmonize regulatory requirements.


June 28, 2020 /BioValleyBIOON/ -- Japanese pharmaceutical company Daiichi Sankyo recently announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) issued a negative opinion on the Marketing Authorization Application (MAA) for pexidartinib. The MAA sought approval for pexidartinib to treat adult patients with symptomatic tenosynovial giant cell tumor (TGCT) who experience severe morbidity or functional limitations and are not suitable candidates for surgical improvement. In the EU, the EMA had previously granted orphan drug designation (ODD) to pexidartinib for the treatment of TGCT.

In the United States, the New Drug Application (NDA) for pexidartinib in the treatment of tenosynovial giant cell tumor (TGCT) is undergoing priority review by the FDA, with a Prescription Drug User Fee Act (PDUFA) target action date of August 3, 2019. Previously,FDAPexidartinib has also been granted Breakthrough Therapy Designation (BTD) and Orphan Drug Designation (ODD) for the treatment of TGCT.

Daiichi SankyoTumorAntoine Yver, M.D., Executive Vice President of Research and Development and Global Head, stated, “We will evaluate the feedback received from the CHMP to determine the appropriate next steps for pexidartinib in the European Union. Despite this setback, we remain confident in the therapeutic potential of pexidartinib for patients with tenosynovial giant cell tumor (TGCT), who often face debilitating symptoms and currently have no approved systemic treatment options.”

Pexidartinib is a novel oral small molecule developed by Plexxikon, the small-molecule structure-based R&D center of Daiichi Sankyo, which effectively inhibits 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 are no systemic therapies available for TGCT. If approved, pexidartinib will become the first and only drug authorized for the treatment of symptomatic TGCT patients with significant morbidity or functional limitations who are not candidates for surgical improvement.

Molecular Structure of Pexidartinib (Image Source: apexbio.cn)

In the United States and the European Union, the regulatory applications for pexidartinib were both based on data from the pivotal Phase III clinical trial, ENLIVEN. This was the first placebo-controlled study to evaluate a systemic therapy in patients with tenosynovial giant cell tumor (TGCT). The results from this study were published on June 19, 2019, in The Lancet, a premier international medical journal.

Data showed that, based on the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, at Week 25 of treatment, the overall response rate (ORR) was 39% in the oral pexidartinib group versus 0% in the placebo group, 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 (up to 17 months).

TGCT, also known as Pigmented Villonodular Synovitis (PVNS) or Giant Cell Tumor of the Tendon Sheath (GCT-TS), is a rare, typically non-malignant condition affecting joints or tendon sheaths.Tumor, may be locally aggressive in some patients. TGCT affects synovial joints, bursae, and tendon sheaths, causing swelling, pain, stiffness, and reduced mobility in the affected joints or limbs. Due to the rarity of TGCT, it is currently unclear how many people are affected annually.Diagnosisto develop this disease.

Currently, the standard of care for TGCT is surgical resection of the tumor. 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.

TGCT is classified into two types: localized type (90%) and diffuse type (10%). The estimated recurrence rate of localized TGCT after complete resection is 15%, while that of diffuse TGCT after complete resection is approximately 20–50%. TGCT affects all age groups and is typically diagnosed between the ages of 20 and 50, depending on the TGCT type. Women are affectedTumorThe likelihood is twice that in males. The diffuse type typically occurs in individuals under 40 years of age, while the localized type usually affects those aged 30–50 years. (Bioon.com)