Belumosudil (1) – Rezurock®

• Clinical trials
  • To assess the extent of the additional benefit of Belumosudil, the pharmaceutical manufacturer submitted the results of the completed ROCKstar (KD025-213) registration trial.
  • The ROCKstar trial is an open-label, randomised, uncontrolled clinical study, multicentre Phase II trial designed to assess the efficacy and safety of Belumosudil in patients with chronic graft-versus-host disease who had received at least 2 and no more than 5 previous lines of systemic therapy.

Adults and children (aged 12 years and over with a body weight of at least 40 kg) with chronic graft-versus-host disease (cGvHD), where other treatment options offer limited clinical benefit, are unsuitable or have been exhausted

• Hint for a non-quantifiable additional benefit, as the scientific evidence does not permit quantification.
• There are therefore no data available for children and adolescents.
• As no suitable comparative data are available, no conclusions can be drawn regarding the extent of the additional benefit.
• mortality
  • In the Rockstar study, 14 deaths (18.2 per cent) occurred.
  • As no suitable comparative data are available, no conclusions can be drawn regarding the extent of the additional benefit.
• Morbidity – cGvHD response
  • In the ROCKstar study, cGvHD response or the overall response rate (ORR) as the primary endpoint; this is defined as the proportion of patients achieving a complete response (CR) or partial response (PR) at any post-baseline assessment time point, relative to baseline (cycle 1, day 1).
  • In the ROCKstar study, a response rate of 74% was achieved; a total of 4 patients also achieved a CR.
  • Notwithstanding the comments on operationalisation, the results for the complete response endpoint in the ROCKstar study do not allow any conclusions to be drawn regarding the extent of the additional benefit, as no suitable comparative data are available.
• Morbidity – Lee Symptom Scale (LSS)
  • The LSS is a tool for assessing symptom burden in adults with cGvHD.
  • For the total score, a median change of –4.4 points was observed by cycle 5, representing a slight improvement compared with baseline.
  • Notwithstanding this, no conclusions can be drawn regarding the extent of the additional benefit based on the results of the ROCKstar study for the Lee Symptom Scale endpoint, as no suitable comparative data are available.
• Morbidity – Corticosteroid withdrawal
  • In the ROCKstar study, the mean prednisone-equivalent dose of corticosteroids at baseline was 0.21 mg/kg/day. During the course of the study, 27.3 per cent of patients achieved corticosteroid withdrawal as defined by the pharmaceutical manufacturer.
  • Notwithstanding this, no conclusion can be drawn from the results of the ROCKstar study regarding the extent of the additional benefit for the endpoint ‘corticosteroid withdrawal’, as no suitable comparative data are available.
• morbidity
  • When considering the results on morbidity as a whole, no conclusions can be drawn regarding the extent of the additional benefit, as no suitable comparative data are available.
• quality of life
  • Quality of life was not assessed in the ROCKstar study.
• Side effects – Total adverse events (AEs)
  • Almost all patients included in the study (98.7 per cent) experienced an adverse event.
• Side effects – Serious adverse events (SAEs)
  • At least one serious adverse event (SAE) occurred in 36 patients (46.8%). The most common SAEs were ‘infections and parasitic diseases’.
• Side effects – Severe adverse events (CTCAE grade ≥ 3)
  • At least one severe adverse event with a CTCAE grade ≥ 3 occurred in 52 patients (67.5%). The most common AEs of grade ≥ 3 were ‘infections and parasitic diseases’, ‘gastrointestinal disorders’ and ‘respiratory, thoracic and mediastinal disorders’.
• Side effects – discontinuation due to AEs
  • In 15 patients (19.5%), an adverse event occurred that led to discontinuation of treatment with belumosudil.
• Side effects
  • When considering the results on side effects as a whole, no conclusions can be drawn regarding the extent of the additional benefit, as no suitable comparative data are available.
• Overall assessment / Conclusion
  • The basis for the benefit assessment of belumosudil for the treatment of chronic GvHD in adults and children (aged 12 years and over with a body weight of at least 40 kg), where other treatment options offer limited clinical benefit, are unsuitable or have been exhausted, are the findings on mortality, morbidity and side effects from the uncontrolled, open-label ROCKstar clinical study.
  • As this is an uncontrolled clinical study, it is not possible to carry out a comparative assessment and thus to quantify the extent of the additional benefit on the basis of these data.

Courtesy translation only, please refer to the German original.