JAKAVI (ruxolitinib) - Graft-versus-host disease (GvHD)

The clinical benefit of JAKAVI (ruxolitinib) 5 mg/mL oral solution and JAKAVI (ruxolitinib) 5 mg tablets is substantial in the MA indication.

Considering:

• the simplicityof its administration due to its tablet and oral solution forms (oral route), enabling the product to be used on an outpatient basis, and with a form suitable for young children;
• available data in adults supporting the presumption of a benefit for the patient, in particular:
  • short-term efficacy data from a comparative, randomised, open-label phase 3 study that demonstrated a superiority of ruxolitinib over the comparator therapies used for the 28-day overall response rate (OR=2.64 [95% CI: 1.65-4.22]) and 56-day overall response rate (OR=2.38 [95% CI: 1.43-3.94]) in patients over 12 years of age with grade II-IV corticosteroid-resistant acute GvHD (REACH 2 study),
  • efficacy data from a comparative, randomised, open-label phase 3 study that demonstrated a superiority of ruxolitinib for the 24-week overall response rate (OR=2.99 [95% CI: 1.86-4.80]) and survival without treatment failure (HR=0.37 [95% CI: 0.27-0.51]) in patients over 12 years of age with moderate to severe corticosteroid-refractory or corticosteroid-dependent chronic GvHD (REACH 3 study);
• pharmacokinetic data supporting the presumption of transposability of the results in the population aged 12 years and older to the paediatric population aged 28 days to 11 years (GvHDa) and aged 6 months to 11 years (GvHDc);
• the results of non-comparative, open-label phase 1/2 and 2 studies (REACH 4 and REACH 5) conducted in paediatric patients evaluating the overall response rate;
• the available safety data (REACH 4 and REACH 5 studies) suggesting a safety profile in paediatric patients similar to that observed in adults patients;
• pharmacokinetic modelling data supporting the presumption of transposability of the results in the population aged 12 years and older to the population aged under 2 years;
• the unmet medical need, due in particular to its liquid formulation suitable for paediatric medicine;

and despite:

• a non-comparative design of paediatric studies, enabling only a non-causal estimation of the effect of JAKAVI (ruxolitinib) +/- combination with other treatments with the same therapeutic purpose, and not of its additional relative efficacy compared to the placebo effect and the natural course of the disease; in addition, this study design authorising the administration of prophylactic treatments and systemic treatments for GvHD in addition to ruxolitinib does not enable the effect of JAKAVI (ruxolitinib) alone to be isolated. In accordance with the SmPC, section 4.2 “Posology and method of administration: JAKAVI can be added to corticosteroids and/or calcineurin inhibitors (CNIs)”;
• the open-label design of these studies, which may have introduced a follow-up bias, particularly for the measurement of subjective criteria, such as response endpoints based on the National Institutes of Health consensus;
• the lack of robust evidence of an effect on overall survival in life-threatening clinical situations;
• the absence of robust data relative to the quality of life of patients, the scope of which would nonetheless remain limited given the open-label nature of the study;
• the use of different dosage forms (tablets, capsules, oral solutions) in the paediatric clinical studies;
• uncertainty with respect to the long-term safety profile in the paediatric population and the important risk of developmental toxicity identified in the RMP;
• uncertainties with respect to the transposability of the data: no clinical data are available for patients under 2 years of age, the low number of children under 12 years of age resistant to corticosteroids or other systemic therapies;

the Transparency Committee deems that the drugs JAKAVI 5 mg/mL oral solution (ruxolitinib) and JAKAVI 5 mg tablets (ruxolitinib) provide a minor clinical added value (CAV IV) in the management treatment strategy for patients aged 28 days to under 12 years with acute graft versus host disease who have inadequate response to corticosteroids or other systemic therapies, and patients aged 6 months to under 12 years with chronic graft versus host disease who have inadequate response to corticosteroids or other systemic therapies.