On 16 August 2022 the President of the Agency for Health Technology Assessment and Tariff System issued the following recommendation:
Recommendation No. 70/2022 of 16 August 2022 of the President of the Agency for Health Technology Assessment and Tariff System on the evaluation of medicine Rezurock (belumosudil) for the indication: treatment of adult and paediatric patients aged 12 years and older with chronic graft-versus-host disease (chronic GVHD) after failure of at least two prior lines of systemic treatment.
The President of the Agency recommends issuing approvals for the reimbursement of Rezurock (belumosudil) for the following indication: treatment of adult and pediatric patients aged 12 and older with chronic graft-versus-host disease (chronic GVHD) after failure of at least two previous lines of systemic treatment, provided that other therapeutic options have been exhausted or are contraindicated.
Grounds for the recommendation
The studies included in the clinical analysis indicate the benefits of using belumosudil, e.g. with respect to the overall response rate (ORR). In a study by Cutler (2021) ORR was 74% (1 x 200 mg) and 77% (2 x 200 mg), depending on the daily drug dose. In a study by Jagasia (2021), ORR in a group of patients who received ≥2 prior lines of treatment was 67% (1 x 200 mg), 63% (2 x 200 mg) and 67% (1 x 400 mg). The duration of response ranged from 38 weeks (Jagasia 2021) to 54 weeks (Cutler 2021).
Moreover, an effect on patients’ overall survival, improvement in quality of life, corticosteroid dose reduction and good drug tolerance were observed. In the study by Cutler (2021), the 2-year survival rate was 89%.
A clinically meaningful improvement in the Lee Symptom Scale (LSS) score, defined as at least 7-point reduction in the total score, was observed in 44–62% patients, depending on the study.
In the study by Cutler (2021), belumosudil was well-tolerated by patients who had undergone previous intensive therapy. The drug proved to be effective in patients with steroid-resistant cGVHD (response was obtained in all organs) and in patients who failed treatment with ibrutinib or ruxolitinib. Patients who previously received ibrutinib and ruxolitinib constituted 34% (n = 45) and 29% (n = 38) of study subjects, respectively.
In a considerable percentage of patients included in the studies, the indication for transplant was acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL). These patients accounted for 37% and 15%, respectively, of the patients included in the Jagasia 2021 study (n = 54) and 40% and 14%, respectively, of the patients included in the Cutler 2021 study (n = 132).
At the same time, both studies were open-label and all participants received belumosudil according to different dosing regimens which prevents a direct comparison of the drug with other therapies.
In a study by Schueller (2022), no risk regarding safety or intolerance to belumosudil as monotherapy or in combination with other drugs (itraconazole, rifampicin, omeprazole, rabeprazole) was identified.
Belumosudil is listed in the NCCN 2021 and LLS 2022 patient guidelines as an optional systemic therapy for patients with more severe symptoms or chronic GVHD with multiorgan involvement after failure of systemic treatment.
Therefore, in patients with chronic GVHD, the therapies available in Poland (e.g. steroids, tacrolimus, mycophenolate mofetil, extracorporeal photopheresis) could be used first and then, in the case of failure or due to contraindications or the patient’s health status, the use of Rezurock could be considered.
It should be noted that GVHD is a severe disease which can lead to death. The guidelines do not provide specific therapies for the subsequent lines of cGVHD treatment and only list the drugs that can be used. GVHD management and duration of treatment depend on the patient’s individual treatment response.
As per the expert’s opinion, the drug would be used in approximately 2 persons with chronic graft-versus-host disease (cGVHD) after failure of at least two previous lines of systemic treatment. The estimated annual cost of belumosudil treatment for these patients would amount to approximately PLN 1,526,806.
Taking into account the position of the Transparency Council and the above arguments, especially the significance of the clinical condition and the ability to meet the patients’ health needs, the reimbursement of the proposed technology is considered justified in the case of failure of previous therapies, provided that other therapeutic options have been exhausted or are contraindicated.