Novità Terapeutiche dal Congresso Nordamericano

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1 Novità Terapeutiche dal Congresso Nordamericano Riunione di aggiornamento Scientifico UOC Fibrosi Cistica - OFFICIUM Dott.ssa Enza Montemitro

2 2 Airways Physiology, Pathophysiology & Defense CFTR Clinical Genetic Counselor Genetics & Model Systems Infection & Microbiology Nursing/Education Nutrition New Therapies Pharmacist Physical & Respiratory Therapy Psychologist/Psychiatrist Research Coordinator Social Work/Psychosocial Transplantation Every journey is different every moment is important

3 3 Airways Physiology, Pathophysiology & Defense CFTR Clinical Genetic Counselor Genetics & Model Systems Infection & Microbiology Nursing/Education Nutrition New Therapies Pharmacist Physical & Respiratory Therapy Psychologist/Psychiatrist Research Coordinator Social Work/Psychosocial Transplantation It s time to Get Happy!

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7 BIOMARKERS 7

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9 9 Emerging Therapies in Cystic Fibrosis: AeroVanc for the Treatment of Chronic MRSA Elliott C. Dasenbrook Medicine and Pediatrics, Case Western Reserve University School of Medicine, Cleveland, OH, USA

10 10 Airways Physiology, Pathophysiology & Defense CFTR Clinical Genetic Counselor Genetics & Model Systems Infection & Microbiology Nursing/Education Nutrition New Therapies Pharmacist Physical & Respiratory Therapy Psychologist/Psychiatrist Research Coordinator Social Work/Psychosocial Transplantation Nucleotide analogs are able to correct the Thermodynamic defect in F508del- CFTR with two different modes of action (USA) Novel therapeutic approach for CF caused by the W1282X premature termination codon (Haggie PM et al, USA) Amplifiers are a new class of CFTR modulators that increase the abudance of CFTR protein and combined with Potentiators and Correctors enhance CFTR Chloride transport activity (Miller J et al, USA) Targeting the ribosome as a novel approach to correcting CFTR Class II Trafficking defects (Oliver KE et al, USA)

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14 14 Potenziatore: aumenta il flusso di ioni attraverso il CFTR presente sulla superficie cellulare Seconds Correttore: aumenta il processamento cellulare e il raggiungimento della superficie cellulare della proteina CFTR ER Hours ER

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17 17 Kalydeco Kalydeco (Ivacaftor): estensione della fascia di età dei pazienti con mutazioni gating (a partire dai 2anni) G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, G1349D Kalydeco (Ivacaftor): mutazione R117H a partire dai 18 anni di età. USA: a partire dai 2 anni. EMA: a partire dai 18 anni (in Europa 350 pazienti adulti) Kalydeco (Ivacaftor): proposta per 23 mutazioni con funzionamento residuo di proteina a partire dai 2 anni di età (2789+5G->A, kbC->T, A->G, 711+3A->G, E56K, P67L, R74W, D110E, D110H, R117C, L206W, R347H, R352Q, A455E, D579G, E831X, S945L, S977F, F1052V, R1070W, F1074L, D1152H, e D1270N)

18 18 Orkambi Orkambi (LUMacaftor/IVAcaftor): The FDA has approved the lumacaftor/ivacaftor combination drug Orkambi for people with cystic fibrosis ages 12 and older who have two copies of the most common mutation, F508del. Nov 2015 Vertex riceve l approvazione dell EU per Orkambi (in Europa pazienti)

19 Disegno dello studio 19 Nello studio TRAFFIC, 559 pazienti sono stati arruolati e 524 hanno completato il trattamento. Nello studio TRANSPORT, 563 pazienti sono stati arruolati e 530 hanno completato il trattamento. I pazienti che hanno completato lo studio hanno potuto iniziare la seconda fase dello studio VX (PROGRESS)

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22 22 Lumacaftor-Ivacaftor in patients with Cystic Fibrosis homozygous for Phe508del CFTR Wainwright CE, Elborn JS, Ramsey BW et al. NEJM 2015 Lumacaftor-Ivacaftor in patients with Cystic Fibrosis homozygous for Phe508del CFTR Rehman AR, UI-Ain Baloch N, Janahi IA NEJM 2015 Long-term Clinical Effects of CFTR Co-Therapy with Lumacaftor/Ivacaftor Christiane De Boeck Dept of Paediatrics, University of Leuven, Belgium The Effect of Correctors and Potentiators on CF Mucus and Its Transportability Steven M. Rowe, George M. Solomon, Susan Birket Division of Pulmonary, Allergy & Critical Care Medicine, UAB at Birmingham, AL, USA

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24 24 What studies are Underway or Starting soon? ORKAMBI 2 studi di fase 3 Omozigosi F508del 6-11 anni Europa e USA pazienti KALYDECO Mutazioni CFTR di classe III età inferiore a 2 anni VX VX studi DF508/DF508 DF508/classe III DF508/funzione residua

25 25 What studies are Underway or Starting soon? VX VX VX-152 (o VX-440) 2 studi fase 1 DF508/DF508 DF508/classe III DF508/funzione residua (fase 2) VX-371 Inibitore di EnaC Studio di fase 2 Farmaco inalato VX-371 Inibitore di EnaC Studio di fase 2 Farmaco inalato + Orkambi

26 26 There is no Health Without Mental Health A Quittner Miami