Kadmon has received final minutes from a March 2018 Type C meeting with the U.S. Food and Drug Administration (FDA) regarding the development pathway for KD025, the company’s Rho-associated coiled-coil kinase 2 (ROCK2) inhibitor, for the treatment of chronic graft-versus-host disease (cGVHD). Based on the FDA’s guidance, Kadmon plans to initiate an open-label, two-arm, pivotal Phase 2 clinical trial to support the potential registration of KD025 in cGVHD.
In the planned pivotal trial (KD025-213), patients will be randomized to receive one of two dose levels of KD025: 200 mg QD or 200 mg BID; 48 patients will be enrolled into each arm. Either KD025 dose may be considered by the FDA for the registrational dose. The study will enroll adults with active cGVHD who have received at least two prior lines of systemic therapy for cGVHD. The primary endpoint is the Overall Response Rate (ORR), defined as the percentage of patients who meet the 2014 National Institutes of Health (NIH) Consensus Conference overall response criteria, supported by a key secondary endpoint of Duration of Response (DOR).
“We are pleased with the FDA’s guidance, which provides us with a clear regulatory path forward to support a submission for potential approval,” said Harlan W. Waksal, M.D., President and CEO at Kadmon. “Furthermore, this trial design allows us to evaluate two dose levels of KD025, either of which could meet the target for potential registration. We look forward to advancing KD025 through this pivotal study.”
KD025 is a selective oral inhibitor of ROCK2, a signaling pathway that mediates cell movement, shape, differentiation and function and is dysregulated in many chronic diseases, including cGVHD. Previously reported data from an ongoing Phase 2 clinical trial of KD025 in cGVHD (KD025-208) demonstrated an ORR of approximately 66%. KD025 was also well tolerated, with no drug-related serious adverse events (SAEs). In October 2017, KD025 received orphan drug designation from the FDA for KD025 in cGVHD.