Distribution of cystic fibrosis patients not eligible to studied CFTR modulators in Europe

Studied Cystic Fibrosis (CF) modulators have been announced to cover 90% of all CF patients. A genotype-agnostic novel therapy for CF is under development, which will focus on people with CFwho have mutations that are not eligible for the approved small molecule modulators and triple combination therapies. The data in the European Cystic Fibrosis Society Patient Registry (ECFSPR) are used to provide a quantitative overview of eligible patients. Patients who are alive and seen during the 2017, or alive and not seenwere considered (excluding France who delivered the data directly to the sponsor). Not considered were patients F508del homozygotes eligible for elexacaftor/tezacaftor/ivacaftor, tezacaftor/ivacaftor, lumacaftor/ivacaftor, or heterozygotes eligible for elexacaftor/tezacaftor/ivacaftor. Neither were patients with at least one of the following mutations: E56 K, P67L, R74W, D110E, D110H, R117C, E193 K, L206W, R347H, R352Q, A455E, D579G, 711 +3A->G, E831X, S945L, S977F, F1052 V, K1060 T, A1067 T, R1070W, F1074L, D1152H, D1270N, 2789+5G->A, 3272-26A->G, 3849+10kbC->T (eligible for tezacaftor/ivacaftor, ivacaftor) and R117H, G178R, S549N, S549R, G551D, G551S, G1069R, R1070Q, G1244E, S1251N, S1255P, G1349D (eligible for ivacaftor). From the 41,264 patients registered in the ECFSPR for the 2017, 4,798 patients (12%) carry a genotype that is not eligible to the currentlyapproved modulators or the triple combo. The percentage of non-eligible patients varies from 2,3% in Ireland to 71,9% in Armenia. 2,954 of these patients are 11 years or older, 1,561 have a FEV1% of predicted value between 40% and 90%. In Europe approximately 88% of the patients will be eligible for the currently approved modulators or triple combo, in some countries this percentage is below 50%. With the ECFSPR data, a realistic and useful overviewcould be created to support the design of a study for patients that are not eligible to the currently available modulator and triple combination therapies.