KALYDECO (ivacaftor) (mucoviscidose enfants >6 ans) en association avec SYMKEVI (tezacaftor/ivacaftor)

Opinions on drugs - Posted on Oct 06 2021

Reason for request

First assessment

Key points

Favourable opinion for reimbursement in the treatment of patients aged

6 years and older who are homozygous for the F508del mutation or who are heterozygous for the F508del mutation

and have one of the mutations in the CFTR gene specified in the MA.

What therapeutic improvement?

Therapeutic improvement in the treatment of cystic fibrosis in patients aged 6 years and older:

homozygous for the F508del mutation,
or heterozygous for the F508del mutation and who have one of the mutations in the CFTR gene specified in the MA.

Role in the care pathway?

The management of cystic fibrosis patients requires the intervention of a multidisciplinary team (primary care physicians, specialist centres, paramedical team with physiotherapist and nurse). Treatment is symptomatic and life-long. It is based on complementary interventions, in particular respiratory and nutritional management and patient education.

Role of the medicinal product in the care pathway

As in children aged 12 years and older, SYMKEVI (tezacaftor/ivacaftor) in combination with KALYDECO (ivacaftor) is a long-term treatment that should be prescribed from the outset in patients with cystic fibrosis (CF) aged 6 years and older who are homozygous for the F508del mutation or who are heterozygous for the F508del mutation and have one of the following mutations in the CFTR gene: P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A→G, S945L, S977F, R1070W, D1152H, 2789+5G→A, 3272 26A→G and 3849+10kbC→T.

In patients homozygous for the F508del mutation, the SYMKEVI (tezacaftor/ivacaftor) and KALYDECO (ivacaftor) combination is a first-line treatment, like ORKAMBI (lumacaftor/ivacaftor).

In the heterozygous patients concerned by the MA indication, the SYMKEVI (tezacaftor/ivacaftor) and KALYDECO (ivacaftor) combination is the reference treatment.

Clinical Benefit

Substantial

The Committee deems that the clinical benefit of SYMKEVI (tezacaftor/ivacaftor) in combination with KALYDECO (ivacaftor) is substantial in the MA indication extension for SYMKEVI (tezacaftor/ivacaftor) 100 mg/150 mg film-coated tablets and KALYDECO (ivacaftor) 150 mg film-coated tablets and in the MA indication for SYMKEVI (tezacaftor/ivacaftor) 50 mg/75 mg film-coated tablets and KALYDECO (ivacaftor) 75 mg film-coated tablets.

Clinical Added Value

moderate

Considering:

the demonstration of a moderate efficacy in terms of absolute change in mean lung clearance index LCI₅ (primary endpoint) at up to 8 weeks of treatment, with a difference of -0.51 points (CI95% [-0.74; -0.29]; p<0.0001) in favour of SYMKEVI (tezacaftor/ivacaftor) in combination with KALYDECO (ivacaftor) compared to placebo in a phase 3 study having included a majority of patients (77.6%) homozygous for the F508del mutation in the CFTR gene and a minority of patients (22.4%) heterozygous for the F508del mutation in the CFTR gene,
the safety profile, which appears to be acceptable in children aged from 6 to 11 years,
the substantial unmet medical need in the absence of an available alternative for these patients heterozygous for the F508del mutation, reported by patient associations,

And despite:

the exploratory results relative to biological, growth and symptomatic parameters and quality of life for SYMKEVI (tezacaftor/ivacaftor) in combination with KALYDECO (ivacaftor),

the Committee considers that, as in patients aged 12 years and older, SYMKEVI (tezacaftor/ivacaftor) in combination with KALYDECO (ivacaftor) provides a moderate clinical added value (CAV III) in the therapeutic management of cystic fibrosis in patients aged 6 years and older who are heterozygous for the F508del mutation and have one of the following mutations in the CFTR gene: P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A→G, S945L, S977F, R1070W, D1152H, 2789+5G→A, 3272 26A→G and 3849+10kbC→T.

minor