Health Canada has approved a third drug by Vertex Pharmaceuticals, Symdeko (tezacaftor/ivacaftor and ivacaftor), to treat a subpopulation of people with cystic fibrosis (CF) – those aged 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:  P67LD110H,  R117C,  L206W,  R352Q,  A455E,  D579G,  711+3A→G,  S945L,  S977F,  R1070W,  D1152H,  2789+5G→A,  3272-26A→G, and 3849+10kbC→T.

The two other drugs approved by Health Canada are Orkambi (ivacaftor and lumacaftor) for patients aged 6 and older with two copies of the F508del mutation in their CFTRgene and Kalydeco (ivacaftor) for patients with G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, G1349D or G970R mutation, or aged 18 and older who have the R117H mutation in the CFTR gene.

All three medications contain ivacaftor, a CFTR potentiator that prolongs the time that activated CFTR channels remain open.

Orkambi and Symdeko also contain medications that enhance the effects of ivacaftor to keep the CFTR channel open, albeit in different ways. Symdeko’s tezacaftor helps the CFTR protein move to the proper spot on cell surfaces while Orkambi’s lumacaftor increases the number of CFTR proteins on the cell surface.

The approval of Symdeko was based on 2 clinical studies, the EVOLVE study1 involving people who have two copies of the F508del mutation and the EXPAND study2 involving people with one F508del mutation and one mutation that results in residual CFTR function.

While the approval is good news for the CF community, it will likely be some time before the drug is available in public drug plans. So far, the Canadian Agency for Drugs and Technologies in Health (CADTH) has been fairly critical of Vertex’s medications. While they did recommend Kalydeco to be on the drug plans (with some caveats), they did not recommend Orkambi. It will be very interesting to see what CADTH thinks of Symdeko.

In the meantime, the CF community remains cautiously optimistic given that the drug could help up to half of the CF populations. In a news release, Elizabeth Tullis, MD, Director of the Toronto Adult Cystic Fibrosis Clinic at St. Michael’s Hospital said, “The approval of Symdeko brings great hope to people with CF and their families, and provides a new therapy for almost 50% of Canadians living with CF.”

 

References

  1. Taylor-Cousar JL, Munck A, McKone Ef, et al. Tezacaftor–Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del. N Engl J Med.2017; 377:2013-2023. DOI: 10.1056/NEJMoa1709846
  2. Rowe SM, Daines C, Ringshausen FC, et al. Tezacaftor–Ivacaftor in Residual-Function Heterozygotes with Cystic Fibrosis. N Engl J Med.2017; 377:2024-2035.DOI: 10.1056/NEJMoa1709847