The US Food and Drug Administration (FDA) has granted breakthrough therapy designation for Daiichi Sankyo and Plexxikon ‘s investigational oral colony stimulating factor-1 receptor (CSF-1R) inhibitor pexidartinib (PLX3397) to treat tenosynovial giant cell tumour (TGCT).

TGCT is a rare, potentially destructive tumour of the joint or tendon sheath and can lead to significant pain, joint destruction, frequent surgery and loss of mobility.

Pexidartinib is an investigational, oral small molecule that potently and selectively inhibits CSF-1R, which is a primary growth driver of abnormal cells in the synovium that causes TGCT.

"For patients with a diffuse form of the condition, the tumour is more difficult to remove and has a high-rate of recurrence, resulting in multiple complicated surgeries and even amputation in some patients."

The breakthrough status for pexidartinib is to treat TGCT where surgical removal of the tumour would be associated with potentially worsening functional limitation or severe morbidity.

Daiichi Sankyo executive vice-president and Development global head Mahmoud Ghazzi said: "Surgery is the primary treatment for TGCT, but for patients with a diffuse form of the condition, the tumour is more difficult to remove and has a high-rate of recurrence, resulting in multiple complicated surgeries and even amputation in some patients.

"We are pleased that the FDA recognises the unmet need for the treatment of TGCT and we look forward to working closely with the gency on the expedited development of this potential non-surgical treatment for patients with TGCT."

The FDA has granted breakthrough status based on results from an extension cohort of a single-arm, multi-centre Phase I trial that evaluated the safety and efficacy of pexidartinib.

The most common treatment-related adverse events observed in the ongoing Phase I trial of pexidartinib included fatigue, hair colour changes, nausea, dysgeusia, and periorbital edema, which rarely led to drug discontinuation.

The company said that the treatment-related severe adverse events included fatigue, diarrhea, anemia, hyponatremia, elevated liver enzymes and neutropenia.

A pivotal Phase III trial of pexidartinib called Enliven is currently enrolling patients with symptomatic TGCT where surgical removal of the tumour would be associated with potentially worsening functional limitation or severe morbidity.