JAYPIRCA (pirtobrutinib) - Chronic lymphocytic leukaemia (CLL)

The clinical benefit of JAYPIRCA (pirtobrutinib) 100 mg, film-coated tablet, is moderate only in monotherapy in the treatment of adult patients with relapsed and refractory chronic lymphocytic leukaemia who have previously been treated with a BTK inhibitor and venetoclax (double refractory). 

Considering:

• the evidence of the superiority of JAYPIRCA (pirtobrutinib) over idelalisib + rituximab or bendamustine + rituximab combinations in terms of progression-free survival (primary endpoint; stratified HR = 583; 95% CI [0.38; 0.89] ; p=0.0105), demonstrated in the BRUIN 20020 trial with a median follow-up of 8.3 months in the pirtobrutinib arm and 6.1 months in the IdelaR or BendaR arm in CLL patients previously treated with iBTK, but with an effect size deemed to be modest;
• the lack of demonstrated superiority in terms of overall survival between the two groups in life-threatening clinical situations;
• the exploratory nature of the quality-of-life analyses;
• the safety profile of JAYPIRCA (pirtobrutinib), marked by a similar proportion of serious AEs (47.4%) compared with the idelalisib + rituximab and bendamustine + rituximab combinations (46.8%), and despite a lower proportion of grade ≥ 3 AEs (57.7% vs 73.4%);
• the overall survival sensitivity analysis, in which patients in the IdelaR or BendaR arms who had switched to the pirtobrutinib arm were censored, and which did not make it possible to determine whether the absence of an effect on overall survival could be explained by a dilution of the effect related to the switch. Consequently, the hypothesis that the treatment had no real effect cannot be ruled out;
• the higher number of deaths in the pirtobrutinib arm than in the IdelaR or BendaR arm (32% versus 27%) in the ITT population;
• the presence in the study of a subgroup of “double-exposed” patients (n = 60 per group), which is close to the reimbursement scope (“double refractory”) without corresponding exactly to it, but with the observation of 26 deaths (43%) in the pirtobrutinib arm, compared with 19 deaths (31%) in the IdelaR or BendaR arm;

The Committee deems that JAYPIRCA (pirtobrutinib) 100 mg, film-coated tablet, provides no clinical added value (CAV V) in relation to the comparators bendamustine + rituximab and idelalisib + rituximab.