Chronic graft versus host disease (cGvHD) is a complication that can occur in about 50% of patients following allo-stem cell transplant. Most cases are mild to moderate, but about 10-15 % of patients develops symptoms that are more severe with significant morbidity and mortality.

“In cGvHD, transplanted immune cells (graft) attack the patient's cells (host), leading to inflammation and fibrosis in multiple tissues, including skin, mouth, eye, joints, liver, lung, esophagus and gastrointestinal tract. Approximately 14,000 patients in the United States are living with cGvHD.”

Patients are typically systemically treated for this debilitating disease with corticosteroids and calcineurin inhibitors (such as e.g., cyclosporin and tacrolimus).

The news that the US Food and Drug Administration approved the compound belumosudil (future brand name: Rezurock) on July 16, 2021 and designated the drug as a Breakthrough Therapy, will therefore be welcomed by those patients with cGvHD. The drug is approved for “the treatment of adult and pediatric patients 12 years and older with cGvHD after failure of at least two prior lines of systemic therapy.” The compound is an oral drug that is the first in a new class of compounds targeting Rho-associated coiled-coil kinase 2 (ROCK2), a pathway that modulates inflammatory response.

The drug’s developer, Kadmon, completed 2 Phase II clinical studies of about 65 patients each  that were dosed either with 200 mg once-a-day or 200 mg taken twice-a day.

“The median time from cGvHD diagnosis was 25.3 months and 48% of patients had four or more organs involved. Patients had cycled through a median of 3 prior lines of systemic therapy and 78% were refractory to their last therapy.”

In other words, this patient cohort was in serious need of a treatment alternative.

The results of these two studies can be summarized as follows:

• “Overall Response Rates (ORR) of 74% with 200 mg once daily  and 77%  with 200 mg twice daily.”
• “Responses were achieved across patient subgroups and complete responses were observed in all organ systems, including in lung. Responses were durable, with a median duration of 54 weeks, which represents the total combined response periods for each patient.”
• “44% of responders maintained their response for ≥1 year.”
• “… clinically meaningful improvement from baseline in the Lee Symptom Scale (LSS) score, a chronic GvHD symptom measurement, with belumosudil was observed in 61% of patients”.
• “During treatment, 65% of patients were able to reduce their corticosteroid dose, with 21% of patients completely discontinuing corticosteroid therapy. In addition, 22% of patients completely discontinued calcineurin inhibitor therapy.”
• “Belumosudil was well-tolerated and adverse events have been consistent with those expected in patients with advanced cGvHD receiving corticosteroids and/or other immunosuppressants.”

The company has announced that the drug will be commercially available by late August 2021. This is, unquestionably, good news for those living with this tough to treat/manage disease.