FDA grants Breakthrough Therapy Designation to pexidartinib for the treatment of TGCT

Daiichi Sankyo and Plexxikon have  announced that the US Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to pexidartinib for the treatment of tenosynovial giant cell tumour (TGCT) where surgical removal of the tumour would be associated with potentially worsening functional limitation or severe morbidity.

TGCT is a rare, usually non-metastatic tumour that affects the synovium-lined joints, bursae, and tendon sheaths, resulting in swelling, pain, stiffness and reduced mobility in the affected joint or limb. It is estimated that TGCT has an annual incidence of 11 cases per million. Patients are commonly diagnosed in their 20s to 50s, and depending on the type of TGCT, women can be up to twice as likely to develop a tumour as men.

Currently, there is no FDA-approved systemic therapy for the treatment of TGCT.

Surgery is currently the primary treatment for TGCT

“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,” said Mahmoud Ghazzi, MD, PhD, Executive Vice President and Global Head of Development for Daiichi Sankyo. “We are pleased that the FDA recognises the unmet need for the treatment of TGCT and we look forward to working closely with the Agency on the expedited development of this potential non-surgical treatment for patients with TGCT.”

The Breakthrough Therapy Designation was granted based on results from an extension cohort of a Phase 1 study that assessed the safety and efficacy of pexidartinib.

“The responses seen in our ongoing phase 1 study provided initial proof-of-concept that selective CSF-1R inhibition with pexidartinib may safely and effectively reduce tumour burden in patients with TGCT, providing the rationale to move directly into a Phase 3 clinical trial,” said Gideon Bollag, PhD, Chief Executive Officer of Plexxikon. “This Breakthrough Therapy Designation represents another significant milestone in our commitment to develop novel targeted agents that address unmet medical needs in rare conditions such as TGCT.”

A Phase 3 study of pexidartinib called ENLIVEN is currently enrolling patients with symptomatic TGCT for whom surgical removal of the tumour would be associated with potentially worsening functional limitation or severe morbidity.