Products

Date: 2018-07-26

Type of information: Positive opinion for the granting of a Market Authorisation in the EU

Product name: Symkevi®(UE)/Symdeko® (USA) in combination with ivacaftor

Compound: tezacaftor/ivacaftor combination

Therapeutic area: Rare diseases - Genetic diseases - Lung diseases

Action mechanism:

• CFTR potentiator. Kalydeco^® (ivacaftor) is a potentiator of the CFTR protein. The CFTR protein is a chloride channel present at the surface of epithelial cells in multiple organs. Ivacaftor facilitates increased chloride transport by potentiating the channel-open probability (or gating) of the G551D-CFTR protein.This oral medicine aims to help the CFTR protein function more normally once it reaches the cell surface, to help hydrate and clear mucus from the airways.
• VX-661 is another CFTR potentiator.

Company: Vertex Pharmaceuticals (USA - MA)

Disease:

• people with cystic fibrosis (CF) ages 12 and older who have two copies of the F508del mutation or one F508del mutation and one residual function mutation that is responsive to tezacaftor/ivacaftor

Latest news:

• • On July 26, 2018, the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for Symkevi^® (tezacaftor/ivacaftor) in a combination regimen with ivacaftor (Kalydeco^®) for the treatment of people with cystic fibrosis (CF) aged 12 and older who either have two copies of the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, or one copy of the F508del mutation and a copy of one of the following 14 mutations in which the CFTR protein shows residual activity: P67L, R117C, L206W, R352Q, A455E, D579G, 711+3A?G, S945L, S977F, R1070W, D1152H, 2789+5G?A, 3272-26A?G, and 3849+10kbC?T.

  The regulatory submission was supported by results from two pivotal Phase 3 studies, EVOLVE and EXPAND, published in the New England Journal of Medicine in November 2017. Results showed treatment with tezacaftor/ivacaftor in combination with ivacaftor provides benefits across different CF populations, including statistically significant improvements in lung function, as determined by absolute change from baseline in ppFEV₁, and with a generally well tolerated safety profile and a lack of increased respiratory adverse events compared to placebo. The most common adverse reactions experienced by patients who received tezacaftor/ivacaftor in combination with ivacaftor in pooled, placebo-controlled Phase 3 studies were headache and nasopharyngitis.

  Tezacaftor/ivacaftor in combination with ivacaftor was approved by the U.S. Food and Drug Administration (FDA) in February 2018 and by Health Canada in June 2018. It is marketed as SYMDEKO™ in the U.S. and Canada.

  Data from the two Phase 3 studies EVOLVE and EXPAND were published in the New England Journal of Medicine in November 2017, the studies enrolled approximately 750 people with CF ages 12 and older with two copies of the F508del mutation or with one F508del mutation and second mutation that is responsive to tezacaftor/ivacaftor. Across both studies, patients treated with tezacaftor/ivacaftor in combination with ivacaftor experienced statistically significant improvements in lung function, as determined by absolute change from baseline in percent predicted forced expiratory volume in one second (ppFEV₁). The treatment was generally well tolerated; the most common adverse reactions (?10%) experienced by patients who received tezacaftor/ivacaftor with ivacaftor in the pooled, placebo-controlled Phase 3 studies were headache (14% versus 12% on placebo) and nasopharyngitis (12% versus 10% on placebo).

  • On June 28, 2018, Vertex Pharmaceuticals announced that Health Canada approved PrSymdeko™ (tezacaftor/ivacaftor and ivacaftor) for treating the underlying cause of cystic fibrosis in people ages 12 and older who have two copies of the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, or who have one copy of the F508del mutation and one of the following mutations in the CFTR gene: P67L, D110H, R117C, L206W, R352Q, A455E, D579G, 711+3A?G, S945L, S977F, R1070W, D1152H, 2789+5G?A, 3272-26A?G, and 3849+10kbC?T. Approval was based on data from two Phase 3 studies (EVOLVE and EXPAND), published in the New England Journal of Medicine in November 2017, that enrolled 744 people with CF ages 12 and older with two copies of the F508del mutation (n=504) or with one F508del mutation and a second mutation predicted to be responsive to tezacaftor/ivacaftor (n=244).

  • On February 12, 2018, Vertex Pharmaceuticals  announced that the FDA approved Symdeko™ (tezacaftor/ivacaftor and ivacaftor) for treating the underlying cause of cystic fibrosis in people ages 12 and older who have two copies of the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene or who have at least one mutation that is responsive to tezacaftor/ivacaftor. Symdeko™ is Vertex's third medicine approved to treat the underlying cause of cystic fibrosis. The European Medicines Agency (EMA) has validated the Marketing Authorization Application (MAA) for the tezacaftor/ivacaftor combination. The company expects approval in the EU in the second half of 2018.

  • On August 24, 2017, Vertex Pharmaceuticals announced the acceptance of its applications for the use of the tezacaftor/ivacaftor combination treatment in people with cystic fibrosis (CF) ages 12 and older who have two copies of the F508del mutation or one F508del mutation and one residual function mutation that is responsive to tezacaftor/ivacaftor by the FDA and the European Medicines Agency (EMA).
• In the United States , the FDA has granted Priority Review of the New Drug Application (NDA) and set an action date of February 28, 2018 . The submissions are supported by positive results from two global Phase 3 studies. The combination treatment also received Breakthrough Therapy Designation.
• In the European Union , the EMA has validated the Marketing Authorization Application (MAA), which confirms that the submission is complete and initiates the centralized review process of approximately 210 days for the Committee for Medicinal Products for Human Use (CHMP) to give an Opinion.

Patents:

Submission of marketing authorization application USA :

Submission of marketing authorization application UE:

Withdrawal of marketing authorization application USA:

Withdrawal of marketing authorization application UE:

US authorization: 2018-02-12

UE authorization:

Favourable opinion UE: 2018-07-26

Favourable opinion USA:

Orphan status USA:

Orphan status UE:

Pediatric exclusivit _USA:

Pediatric exclusivity UE: