Daiichi Sankyo has achieved a significant milestone in rare disease treatment with the FDA approval of pexidartinib (Turalio), marking the first-ever approved drug therapy for tenosynovial giant cell tumour (TGCT). This breakthrough provides hope for patients with this rare joint and tendon tumor, who previously relied solely on surgical intervention.
Disease Impact and Unmet Need
TGCT, also known as pigmented villonodular synovitis (PVNS) or giant cell tumour of the tendon sheath (GCT-TS), affects approximately 11 people per million annually in the United States. Patients often experience debilitating symptoms including pain, stiffness, and restricted movement, which can lead to severe disability. While surgery has been the standard approach, many tumors recur over time, and some patients are not eligible for surgical intervention.
Clinical Trial Results and Mechanism
The FDA's approval is supported by compelling data from the phase III ENLIVEN study, which enrolled 120 TGCT patients. The trial demonstrated significant efficacy:
- 38% overall response rate (ORR) in the pexidartinib group
- 15% achieved complete response
- 23% showed partial response
- No responses observed in the placebo group
Notably, 22 out of 23 responders maintained their response for six or more months, with 13 responses lasting 12 months or longer. Pexidartinib works by inhibiting CSF1R, KIT, and FLT3, three molecular targets crucial for immune responses against tumor cells.
Safety Considerations and Risk Management
The FDA approval comes with important safety measures. The drug carries a boxed warning regarding the risk of serious and potentially fatal liver injury. To manage these risks, the FDA has implemented a Risk Evaluation and Mitigation Strategy (REMS) program, requiring careful liver function monitoring throughout treatment.
This safety concern had previously led to a temporary suspension of the drug's development in 2015. However, the FDA's advisory committee determined that the drug's efficacy in this rare tumor type warranted approval with appropriate risk management measures.
Therapeutic Implications
While pexidartinib may have limited commercial potential due to TGCT's rarity and safety considerations, its approval represents a significant advancement in treating this challenging condition. The drug's development program remains focused on TGCT, with no current plans for expansion into additional indications.
For Daiichi Sankyo, this approval provides a modest positive development following the recent FDA rejection of their acute myeloid leukemia drug quizartinib, despite its approval in Japan.
