KALYDECO 150 mg (ivacaftor)

Key points

Favourable opinion for reimbursement in the treatment of cystic fibrosis (CF) in patients aged 12 years and older who are heterozygous for the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and who have one of the gating mutations or a residual function mutation.

What therapeutic improvement?

Therapeutic improvement in management of cystic fibrosis.

Role in the care pathway?

The management of cystic fibrosis patients requires the intervention of a multidisciplinary team (cystic fibrosis resource and expertise centres, 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. Respiratory management involves:

• daily respiratory physiotherapy,
• aerosol therapy, with:
• inhaled dornase alfa (PULMOZYME), for patients aged 5 years and older, which provides a modest improvement in respiratory function and in the number of exacerbations requiring intravenous antibiotic therapy. It must be followed by a 30-minute respiratory physiotherapy session.
• based on the available data, it is not possible to recommend the routine prescription of inhaled corticosteroids and bronchodilators. A beta-2-mimetic may be offered in the event of exacerbations, or in the long-term during stable periods (with regular reassessment of the clinical benefit), or in nebulised form, with short-acting beta-2-mimetics, before starting the physiotherapy session, in order to improve bronchial drainage.
• antibiotic treatment is required in the event of exacerbation or chronic infection, in successive courses, or as a long-term treatment. The other symptomatic treatments for cystic fibrosis respiratory disorders are short courses of oral corticosteroids, after a 2-week course of antibiotics prescribed for exacerbation, if there is no clinical and/or functional improvement (expert opinion), or in the event of allergic bronchopulmonary aspergillosis.

Lung, or even liver transplantation may be offered as a last resort in advanced forms of the disease.

Nutritional management includes a high-calorie, normal-lipid diet with intake of lipid-soluble vitamins (A, D, E, K) and trace elements (Iron, Zinc, Selenium), sodium chloride supplementation and external compensation for pancreatic insufficiency through the intake of pancreatic extracts.

There are two medicinal therapies targeting the F508del mutation in the CFTR gene and one of the gating mutations or the residual function mutation:

• KALYDECO (ivacaftor) indicated as monotherapy only for the treatment of patients with a gating mutation, i.e. adults, adolescents, and children aged 4 months and older and weighing 5 kg or more with cystic fibrosis who have an R117H CFTR mutation or one of the following gating (class III) mutations in the CFTR gene: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N or S549R.
• KALYDECO (ivacaftor) in combination with SYMKEVI 100 mg/150 mg (tezacaftor/ivacaftor) tablets is the reference treatment for patients aged 6 years and older who are heterozygous for the F508del mutation and have one of the following residual function mutations in the CFTR gene: P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A→G, S945L, S977F, R1070W, D1152H, 2789+5G→A, 3272- 26A→G et 3849+10kbC→T.

The optimal treatment duration for these treatments is not known.

Role of the medicinal product in the care pathway

Considering the demonstrated clinical and biological benefit compared to SYMKEVI (tezacaftor/ivacaftor) in combination with KALYDECO (ivacaftor) for patients with a residual function mutation or to KALYDECO (ivacaftor) for patients with a gating mutation, KAFTRIO (ivacaftor/tezacaftor/elexacaftor) in combination with KALYDECO (ivacaftor) is the first-line treatment of cystic fibrosis in patients who are heterozygous for the F508del mutation in the CFTR gene and who have one of the gating mutations or a residual function mutation. It is a long-term treatment that should be prescribed from the outset in these patients.

The optimal duration for this treatment is not known.