Kadmon Announces Interim Phase 2 Data of KD025 in Chronic Graft-Versus-Host Disease
- Category: Small Molecules
- Published on Tuesday, 11 July 2017 14:41
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Overall Response Rate of 71%, with a Favorable Safety Profile
NEW YORK, NY, USA I July 11, 2017 I Kadmon Holdings, Inc. (NYSE:KDMN) (“Kadmon” or the “Company”) today announced positive interim results from its ongoing Phase 2 clinical trial evaluating KD025, the Company’s Rho-associated coiled-coil kinase 2 (“ROCK2”) inhibitor, in patients with previously treated chronic graft-versus-host disease (“cGVHD”), a serious complication following allogeneic bone marrow or stem cell transplantation. In a preliminary analysis, KD025 demonstrated a favorable safety and tolerability profile in all patients and an overall response rate (“ORR”) of 71%.
KD025-208 is an ongoing Phase 2 clinical trial evaluating the safety, tolerability and activity of KD025 in adults with steroid-dependent or steroid-refractory cGVHD and active disease. The dose-finding study includes 48 patients divided into three cohorts at different dose levels (KD025 200 mg QD, 200 mg BID and 400 mg QD), enrolled sequentially following a safety assessment of each cohort.
In a preliminary analysis of data from the first cohort, KD025 200 mg QD (n=17), KD025 demonstrated clinically meaningful responses in cGVHD patients, with an ORR of 71% (12/17), which includes complete and partial responders. Of responders remaining on KD025 through week 24, 7 of 8 (88%) sustained responses. In addition to the 12 responders, two patients have stable disease and remain on KD025 through week 24. Overall clinical benefit (response and stable disease) occurred in 82% (14/17) of patients. Sixty-seven percent (67%; 8/12) of responders saw an improvement in symptoms as measured by the Lee cGVHD Symptom Scale score. To date, no drug-related serious adverse events (SAEs) have been recorded, and no drug-related elevations in liver function tests have been observed. Importantly, 67% (8/12) of responders had reduction of steroid doses and 67% (4/6) of patients had reduction of tacrolimus doses.
“These positive interim findings indicate activity and a favorable safety profile of KD025 in cGVHD, a fatal disease with no approved therapies,” said John L. Ryan, M.D., Ph.D., Executive Vice President, Chief Medical Officer 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.”
“We are encouraged by these initial activity and safety results, which support the potential of KD025 to treat this unmet medical need,” said Harlan W. Waksal, M.D., President and Chief Executive Officer of Kadmon. “Of note, these data are from the lowest dose of KD025 being studied, and we look forward to further exploring KD025 activity and safety in the two additional higher-dose cohorts.”
R&D Day and Webcast Information
cGVHD is a common and often fatal complication following allogeneic bone marrow transplantation and hematopoietic stem cell transplantation, which are procedures that are often used to treat patients with cancers such as myeloma or leukemia. With cGVHD, transplanted immune cells (graft) attack the patient’s body (host), leading to inflammation and fibrosis in multiple tissues, including skin, mouth, eye, joints, liver, lung and digestive tract.
KD025 is a selective oral inhibitor of ROCK2, a signaling pathway implicated in the pathogenesis of autoimmune and fibrotic diseases. KD025 is being studied in three ongoing Phase 2 clinical trials: a placebo-controlled trial in moderate to severe psoriasis, an open-label trial in idiopathic pulmonary fibrosis and an open-label trial in cGVHD.
About the Study
KD025-208 is an ongoing Phase 2 study evaluating the safety, tolerability and activity of KD025 in 48 patients with steroid-dependent or steroid-refractory cGVHD and active disease. The primary endpoint is KD025 activity at 24 weeks in terms of ORR, as defined by the 2014 National Institutes of Health (NIH) Consensus Response Criteria for overall response. Secondary endpoints include changes in corticosteroid and calcineurin inhibitor dose. Exploratory endpoints include change in symptom burden or bother using the Lee cGVHD Symptom Scale.
Enrollment in the first cohort (KD025 200 mg QD) is complete and enrollment in the second cohort (200 mg BID) is nearly complete, with 15 of 16 patients enrolled. The safety assessment of the 200 mg BID cohort is complete and supports initiating enrollment in the 400 mg QD cohort. Additional study results will be submitted for presentation at upcoming scientific conferences.
About Kadmon Holdings, Inc.
Kadmon Holdings, Inc. is a fully integrated biopharmaceutical company focused on developing innovative products for significant unmet medical needs. We have a diversified product pipeline in autoimmune and fibrotic diseases, oncology and genetic diseases.