Symkevi Approved in EU for CF Patients with Two F508del Mutations, or One Plus a Minimal Function Mutation

Symkevi (tezacaftor/ivacaftor combo), by Vertex Pharmaceuticals, has been approved in the European Union for patients with cystic fibrosis (CF) ages 12 or older who carry F508del mutations.

Importantly, the European Commission’s decision to grant marketing authorization makes Symkevi the first treatment in Europe for CF patients with only one F508del copy plus another mutation that confers minimal function to CFTR, the defective gene in CF.

The combination therapy, sold under the brand name Symdeko, was approved in the U.S. and in Canada earlier this year for this same patient group.

Symkevi in combination with Kalydeco (ivacaftor) was recommended for approval by the Committee for Medicinal Products for Human Use (CHMP),  a branch of the European Medicines Agency’s (EMA) in July.

“The authorization of tezacaftor/ivacaftor in combination with ivacaftor is welcome news for European CF patients, their families and everyone involved in their treatment and care,” Harry Heijerman, a professor and head of department of pulmonology at the University Medical Centre Utrecht, the Netherlands, said in a Vertex press release.

He added this decision “is especially important for patients with residual function mutations and those who do not tolerate Orkambi (lumacaftor/ivacaftor).” Also marketed by Vertex, Orkambi is indicated only for CF patients with two copies of an F508del mutation in the CFTR gene, the most common CF mutation.

Symkevi will be available as film-coated tablets containing 100 mg tezacaftor and 150 mg ivacaftor, and is approved for CF patients carrying two F508del mutations or one such mutation plus a residual mutation. In the latter case, the treatment is specifically intended for those with an F508del mutation copy and one of the following 14 residual function mutations: P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A→G, S945L, S977F, R1070W, D1152H, 2789+5G→A, 3272-26A→G, and 3849+10kbC→T.

Europe’s green-light was based on positive results obtained in two Phase 3 trials — EVOLVE (NCT02347657) and EXPAND (NCT02392234) — which demonstrated the ability of Symkevi in combination with Kalydeco to significantly benefit CF patients over 24 weeks and eight weeks of treatment, respectively.

The combo treatment was shown to increase lung function, as seen by a higher predicted forced expiratory volume in one second, or ppFEV1 — the amount of air a person can expel in one second after a deep breath. The therapy also lowered the rate of CF flares, and improved patients’ weight and quality of life.

Treatment was generally well-tolerated, with the most common adverse reactions in patients given the combination being headache and nasopharyngitis (inflammation of pharynx and nasal passages).

“Today marks an important milestone for many CF patients in Europe, including those who so far have had no available option to treat the CFTR protein defect responsible for their disease,” said Reshma Kewalramani, MD, executive vice president, global medicines development and medical affairs, and chief medical officer at Vertex.

“With today’s Marketing Authorization, we are rapidly moving towards treating 90 percent of CF patients,” Kewalramani added.