Phase 2 Study of KD025 Shows Encouraging Clinical Response in Patients with Graft-versus-host Disease

Phase 2 Study of KD025 Shows Encouraging Clinical Response in Patients with Graft-versus-host Disease

Treatment with KD025 is safe and effectively reduces the manifestations of graft-versus-host disease in patients receiving steroids for the condition, or whose condition worsened while on steroids, Kadmon Holdings announced.

Those findings were revealed recently during the Blood & Marrow Transplantation Tandem Meetings in Salt Lake City and published in presentation titled, “Initial Results of KD025-208: A Phase 2a Open-Label Clinical Trial of KD025 for Steroid-Dependent Chronic Graft Versus Host Disease (cGVHD).

Stem cell transplant is a common treatment for patients with blood cancers like lymphoma. While this is the only curative treatment for some patients, the approach may be associated with serious side effects. Among them, is the development of graft-versus-host disease, a condition where the transplanted immune cells attack the patient’s healthy tissues.

Chronic graft-versus-host disease (cGVHD) is a leading cause of morbidity and mortality after transplant.

KD025 is a small inhibitor of the Rho-associated coiled-coil kinase-2 (ROCK2). Preclinical studies have shown that the medicine targets the excess inflammation and fibrosis associated with cGVHD, improving multiple organs affected by the condition.

In an attempt to determine KD025’s effectiveness and safety profile, Kadmon is conducting a Phase 2 clinical trial (NCT02841995) that enrolled 48 cGVHD patients. Participants in the trial received KD025 as two 100 mg capsules once daily, two 100 mg capsules twice daily, or four 100 mg capsules once daily.  Patients were treated for 24 weeks.

Results from the first dosing group revealed that 71% of patients responded to the treatment. Three patients discontinued KD025 treatment prior to 24 weeks, but each of those patients had demonstrated responses prior to study discontinuation.

By week 24, 86% of patients had some sort of benefit from the treatment, and 57% had achieved either a partial or a complete response.

There were no treatment-related serious adverse events in this group. KD025 was shown well-tolerated and the overall adverse event profile was consistent with cGVHD.

Interestingly, at 24 weeks, 57% of patients had a reduction in steroid dose and 67% had a reduction in tacrolimus dose, another immunosuppressive agent used to treat cGVHD.

“KD025 was also well tolerated, and many patients have been able to reduce or discontinue steroids and other immunosuppressants, thereby helping to avoid their adverse effects and improve patients’ quality of life,” Aleksandr Lazaryan, MD, MPH, PhD, said in a press release. Lazaryan is assistant professor of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota and a study investigator.

Eleven of 14 patients chose to remain on KD025 treatment after 24 weeks. In addition, KD025 demonstrated an overall clinical benefit rate, as measured by response or stable disease, in 88% of all cGVHD patients in this group.

“Treatment of cGVHD with KD025 demonstrated encouraging clinical responses and a favorable safety profile in patients with steroid-dependent cGVHD,” the researchers concluded.

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