Haris Ali, MD: Belumosudil is a ROCK2 inhibitor. ROCK2 is a Rho-associated coiled protein kinase-2. Its inhibition leads to downregulation of STAT3 and STAT5 phosphorylation, which in turn leads to a shifting of balance of TH17 [T helper 17 cells] and T-reg [regulatory T cells] more toward T-reg, which dampens the immune activity and leads to a decrease in the GVHD [graft-vs-host disease]. It also increases the pro-inflammatory cytokines and decreases the fibrosis that is happening in chronic GVHD.

The ROCKstar trial included patients who were 12 years old and older and had received 2 to 5 prior lines of treatment. It had 2 different doses scheduled, 200 mg daily and 200 mg twice a day. The primary end point was best overall response rate, and the secondary end points were duration of response, changes in the Lee Symptom Scale score, and failure-free survival. Overall, 65 of the patients had more than 3 lines of treatment, and the best overall response was quite good, 74% for patients with the 200-mg dose, which was the FDA approved dose. In all subgroups, patients with different organ involvement, responses were seen, including a patient who was previously on ruxolitinib and ibrutinib. The median duration of response was 54 weeks and overall failure-free survival was 75%.

This study included patients who were already on the FDA-approved agent, for example, Jakafi [ruxolitinib] and ibrutinib. Several patients who are on this treatment did not respond. Having responses in those patients is an unmet need, so it helps to have an option for these patients who have progressed on prior lines of treatment.

It seems quite safe and efficacious. It’s just recently approved, almost half a year ago. We have used it in the trial and outside the trial, and we have seen the same safety and efficacy in our patients.

Transcript edited for clarity.