FDA approves belumosudil for the treatment of patients with cGvHD

On July 16, 2021, it was announced that the U.S. Food and Drug Administration (FDA) approved the use of belumosudil (200 mg once daily) for the treatment of adults and pediatric patients ≥12 years with chronic graft-versus-host disease (cGvHD) who have failed ≥2 prior lines of systemic therapy.¹ The approval was based on the results of the phase II ROCKstar trial, which were previously published on the GvHD Hub.

Belumosudil

• An oral, small molecule inhibitor of Rho-associated coiled-coil kinase 2 (ROCK2), a signaling pathway that modulates inflammatory responses and fibrotic processes.¹
  • Helps resolve immune dysregulation by down-regulating pro-inflammatory Th17 cells and increasing regulatory T cells.²

ROCKstar trial results pertinent to this approval¹

• A phase II, randomized, multicenter trial, evaluating the safety and efficacy of once-daily or twice-daily belumosudil (200 mg) for the treatment of patients ≥12 years old who had active cGvHD and had received 2–5 prior lines of systemic cGvHD therapy.
• Sixty-five patients were treated in the once-daily arm. The median time from diagnosis was 25.3 months, with a median of three prior lines of therapy.
  • 48% of patients had ≥4 organs involved.
  • 78% of patients were refractory to last therapy.
• By Cycle 7 Day 1 of treatment, the overall response rate was 75% (95% confidence interval, 63–85).
  • A complete response was achieved in 6% of patients.
  • A partial response was achieved in 69% of patients.
• No new systemic therapy was required for at least 12 months following response in 62% of responders.
• Median duration of response (from first response to progression, death, or new systemic therapies for cGvHD) was 1.9 months.
• 52% of patients also had a clinically meaningful improvement from baseline in the Lee Symptom Scale score.
• Adverse events were consistent with those expected in patients with advanced cGvHD receiving corticosteroids and/or other immunosuppressants.

Belumosudil was shown to be efficacious, with robust and durable responses, and was well tolerated. This approval makes belumosudil the first and only ROCK2 inhibitor to be approved in the U.S. and therefore represents a new treatment paradigm for patients with cGvHD, including those with difficult-to-treat manifestations like fibrosis.