- Kadmon Holdings has used its Research & Development Day in New York to trumpet an overall response rate of 71% for its ROCK2 inhibitor in a preliminary analysis of the first cohort of previously treated chronic graft-versus-host disease (cGVHD).
- The Phase 2 clinical trial, KD025-208, is ongoing in 48 patients with steroid-dependent or steroid-refractory cGVHD and active disease, and involves three different dose levels of the drug. For the 200 mg once daily dose, 12 of 17 patients (71%) showed a clinically meaningful response. Seven of eight (88%) of the patients who responded and remained on KD025 until week 24 had a sustained response.
- For the 200 mg twice-daily dose, responses began at two months rather than four-to-five months, and six of nine patients were responding at six weeks, suggesting a faster onset. There have been no drug-related serious adverse events reported, and no drug-related increases in liver function tests, for either dose.
After a disappointing initial public offering and a tough debt load looming for 2018 and 2019, Kadmon spent the latter half of 2016 putting its house in order, with a credit agreement renegotiation, staff cuts and optimization of its sales strategies. While these changes work in the background, in the foreground the company spent its R&D day yesterday celebrating some good news for KD025, its Rho-associated coiled-coil kinase 2 (ROCK2) inhibitor, which has shown similar efficacy to other drugs in development such as Imbruvica (ibrutinib) and Jakafi (ruxolitinib).
"These positive interim findings indicate activity and a favorable safety profile of KD025 in cGVHD, a fatal disease with no approved therapies," said John Ryan, CMO of Kadmon. “Steroids are the current standard therapy for cGVHD and have severe side effects associated with long-term use. We are pleased to see that the majority of patients in the first cohort have been able to reduce their steroid doses, indicating that KD025 potentially offers a well-tolerated treatment option for cGVHD patients."
The company will roll out further data for the other two cohorts, with more results on twice-daily dosing at 200 mg, and data on once daily dosing at 400 mg, during 2018. According to Jefferies analysts, Kadmon will seek breakthrough designation for KD025 by the end of 2017, and begin a clinical trial in newly diagnosed cGVHD in early 2018.
KD025 is also being assessed in a placebo-controlled Phase 2 clinical trial in moderate to severe psoriasis, and an open-label Phase 2 clinical trial in idiopathic pulmonary fibrosis. The company's pipeline includes tesevatinib, in Phase 2 for non-small cell lung cancer and glioblastoma, and in Phase 2 and 3 for polycystic kidney disease.
Chronic graft-versus-host disease (cGVHD) is a complication of allogeneic bone marrow transplantation and hematopoietic stem cell transplantation, often used to treat myeloma and leukemia. Symptoms affect skin, mouth, liver, eyes, gastrointestinal tract, vagina, esophagus, musculoskeletal tissue and lungs. While the global GVHD market is still a relatively small one, worth around $360 million in 2016, rising to an estimated $640 million by 2026, according to Visiongain. cGVHD affects up to 50% of patients who survive longer than three months post-transplant and has a major impact on quality of life in otherwise successfully treated patients.