Favourable opinion for reimbursement only for the treatment of invasive candidiasis in non neutropenic adults.
Unfavourable opinion for reimbursement in the other situations covered by the MA indication.
Clinical Benefit
Substantial
The Committee deems that the clinical benefit of REZZAYO (rezafungin) is substantial only in the treatment of invasive candidiasis in non-neutropenic adults.
Insufficient
The Committee deems that the clinical benefit of REZZAYO (rezafungin) is insufficient to justify public funding cover in view of the available alternatives in the other MA situations (neutropenic adults).
Clinical Added Value
no clinical added value
Considering:
the partially met medical need in adult patients with severe invasive candidiasis, particularly in the event of concomitant neutropenia;
the demonstrated non-inferiority of rezafungin compared to caspofungin in terms of (ITTm analysis):
global response at D14 (EMA endpoint): 59.1% (55/93) versus 60.6% (57/94), i.e. an adjusted difference = -1.1%, CI95% [-14.9; 12.7],
all-cause mortality at D30 (FDA endpoint): 23.7% (22/93) versus 21.3% (20/94), i.e. an adjusted difference of 2.4%, CI95% [-9.7; 14.4];
an acceptable safety profile but marked by adverse events, such as injection-related reactions, tremor and phototoxicities;
but:
a very wide non-inferiority bound in terms of global response and mortality compared to caspofungin, accepting a loss of efficacy risk of up to 20% compared to the comparator (non inferiority threshold scheduled in the protocol);
the absence of a reduction in mortality rate compared to caspofungin (superiority still to be demonstrated);
a limited transposability of the results in the population of interest with a more severe prognosis, in particular:
the non-inclusion of severe hepatic impairment or with a complex infection (endocarditis, osteoarticular infection, endophthalmitis, central nervous system infections, chronic disseminated candidiasis, urinary infection),
a confirmed diagnosis of invasive candidiasis in only a third of patients,
a low number of neutropenic patients (absolute neutrophil count < 500 cells/µL): 8/100 in the rezafungin group and 5/99 in the caspofungin group,
an APACHE score ≥ 20 in approximately 17% of patients;
the absence of data on treatment failures and/or resistances of the strains selected in the clinical trials; the Committee considers that REZZAYO (rezafungin) provides no clinical added value (CAV V) in the treatment of invasive candidiasis in non-neutropenic adults.
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