Sun's Concert hits bum note as FDA imposes partial hold 2 months after $576M buyout

Sun Pharma’s $576 million Concert Pharmaceuticals buyout has rapidly run onto the rocks. Two months after closing the deal, the Indian drugmaker has revealed (PDF) a blood clot has triggered a partial FDA hold on development of Concert’s key candidate.

The blood clot, a pulmonary embolism, occurred in a patient who received the 12-mg, twice daily dose of the oral JAK1/2 inhibitor deuruxolitinib in an open-label extension to a phase 3 trial in alopecia areata, an autoimmune disease that causes hair loss. After learning of the adverse event, the FDA imposed a partial clinical hold that requires Sun to stop the 12-mg twice daily dose.

Patients can carry on taking the 8-mg twice daily dose, and Sun is taking “immediate steps” to transition participants in the open-label studies to the lower dose. No patients have suffered thrombotic events such as pulmonary embolisms at the 8-mg dose.

Concert brought deuruxolitinib through phase 2 and 3 clinical trials in alopecia areata without seeing any thrombotic events. The biotech’s two phase 3 alopecia areata clinical trials tested deuruxolitinib at both the 8-mg and the 12-mg doses. 

Reassured by the lack of thrombotic events up to the open-label extension, Sun said it remains confident in the potential of deuruxolitinib to treat alopecia areata and plans to work with the FDA to resolve the concerns raised by the pulmonary embolism. 

The concerns are, in part, a reflection of the safety problems associated with the broader JAK class. Last year, the European Medicines Agency recommended caution when treating patients with risk factors for blood clots in the lungs and in deep veins because of evidence JAK inhibitors can cause thromboembolic events. 

Concert highlighted the lack of pulmonary embolisms or deep vein thromboses as a strength of its phase 3 data. Eli Lilly’s JAK inhibitor Olumiant, which won approval in alopecia areata last year, carries a black box warning in the U.S. because of safety issues including increased incidence of pulmonary embolism. 

Lilly saw no cases of venous thromboembolism (VTE), a term that covers deep vein thrombosis and pulmonary embolism, in its two phase 3 alopecia areata trials. There was one case of VTE in an extended safety analysis.