Kadmon reports that the first patient group treated in a Phase 2 trial of its drug KD025 for chronic graft-versus-host disease after going through bone marrow or stem cell transplants, has responded well to the treatment, with more than 70 percent of participants having a partial or complete response.
The study group is the first of three that will receive increasing doses of KD025 in the trial, which so far has shown the treatment to have a good safety profile, offering hope to patients with myeloma and other conditions that required a transplant.
“These positive interim findings indicate activity and a favorable safety profile of KD025 in cGVHD [chronic graft-versus-host disease], a fatal disease with no approved therapies,” John L. Ryan, MD, PhD, said in a press release. Ryan is executive vice president and 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,” he added.
Chronic graft-versus-host disease occurs when transplanted immune cells, which physicians refer to as the graft, attack the patient’s body, which is then referred to as the host. This causes inflammation and fibrosis in numerous tissues and organs, including skin, mouth, eye, joints, liver, lung, and digestive tract.
KD025 exerts its actions by blocking a molecule called ROCK2, involved in these processes.
The KD025-208 study (NCT02841995) has recruited 17 previously treated patients who received 200 mg of the drug once a day. Six months later, researchers evaluated their response, showing that 71 percent — or 12 of the 17 participants — had either a partial or complete response. Of the responding patients who remained in the study for six months, seven of eight, or 88 percent had a sustained response.
Kadmon also reported that two patients had stable disease during the trial, adding up to a total of 82 percent of patients who benefited from the treatment. Two-thirds of responders had fewer symptoms, measured by the Lee cGVHD Symptom Scale.
So far, the trial not been burdened by serious adverse events, and tests indicate that the drug has not triggered liver toxicity.
Chronic graft-versus-host disease is typically treated with steroids, and 67 percent of responding patients could taper their steroid doses during the study, speaking to the drug’s efficiency. Four out of six treated with tacrolimus could reduce that dose, as well.
“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, MD, president and CEO 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,” he added.
The trial is designed so that each dose group is examined before the dose is raised. Next, researchers will study a group of patients who will receive 200 mg of KD025 twice daily. Last, a dose of 400 mg once daily will be studied.