Daiichi Sankyo scores landmark FDA OK for rare tumor drug — albeit with restrictions
Daiichi Sankyo finally has a regulatory win to celebrate as the FDA sanctions a careful, restricted rollout of pexidartinib, to be marketed as Turalio.
Throughout internal reviews and the advisory committee panel, where it has appeared side by side quizartinib — the acute myeloid leukemia drug slapped down by regulators in June — pexidartinib has emerged as the drug candidate with better chances for approval as it represents a landmark treatment option for a rare tumor. Tenosynovial giant cell tumors are typically benign but can be debilitating as they affect small and large joints.
The Japanese drugmaker notes that the approval only covers “select” patients — those for whom surgery is not an option. It also comes with a strict REMS program and a boxed warning for hepatoxicity, an issue that has plagued late-stage clinical trials. To mitigate the risk of potentially fatal liver injury, the FDA has mandated that only certified healthcare providers prescribe the drug, while Biologics by McKesson will be the exclusive specialty pharmacy provider.
During a Phase III study, 13% of the drug arm dropped out of the study due to serious adverse events, compared to 1.7% in the control group. All told, there were two irreversible cases of cholestatic liver injury among 768 patients who received the drug, one ultimately resulting in death and the other in liver transplant.
But the regulators clearly agreed with the outside experts in that the benefits outweighed the risks — even if some data were missing after week 25.
“TGCT can cause debilitating symptoms for patients such as pain, stiffness and limitation of movement. The tumor can significantly affect a patient’s quality of life and cause severe disability,” Richard Pazdur, director of the FDA’s Oncology Center of Excellence, stressed in a statement.
Pexidartinib works by inhibiting CSF1R, or colony-stimulating factor 1 receptor. The pivotal study suggests that it induced a tumor response rate of 38% compared to 0% in the placebo group, with an overall response rate reaching 56% (again versus 0% for placebo).
“(W)e are committed to educating patients and the healthcare providers who care for them about the benefits and risks associated with TURALIO to ensure appropriate prescribing and monitoring.” Antoine Yver, global head of oncology R&D at Daiichi Sankyo, said in the announcement.