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Page 1 of 3The University of Alabama at BirminghamSteven Rowe, M.D.UAB NewsUAB clinical trials pave way to new cystic fibrosis drugBy StaffPublished 05/15/2017Source: https://www.uab.edu/news/research/item/8312-uab-clinical-trials-pave-way-to-new-cystic-fibrosis-drugWritten by Viktoria HavasiMedia contact: Jeff Hansen, jeffhans@uab.eduImagine breathing through only a tiny straw.That is what life is like for people with cysticfibrosis, which includes about 30,000 peoplein the United States, making cystic fibrosis themost common lethal genetic disease in thecountry.Though the CFTR gene responsible for thedisease was discovered in 1989, it has takenresearchers nearly 25 years to develop the firstcausative treatment for one type of cysticfibrosis. For many cystic fibrosis patients,specific treatment for their individual gene isstill not available.A step forward came in March as VertexPharmaceuticals announced successful PhaseIII trials that were conducted partly at theUniversity of Alabama at Birmingham. StevenRowe, M.D., a professor in the Division ofPulmonary, Allergy and Critical CareMedicine, UAB School of Medicine, was partof the international leadership team. Thisnewly developed drug — a “corrector-potentiator” combination therapy using the Vertex drugs Tezacaftor and Ivacaftor — may lead to a better futurefor cystic fibrosis patients, a future in which they may not need to struggle with every breath.According to Rowe, the new Tezacaftor/Ivacaftor combination drug is an extremely exciting development incystic fibrosis therapy for two reasons. First, this new combination drug did not have any of the adversepulmonary effects associated with another Vertex drug, Orkambi (Lumacaftor/Ivacaftor), aimed at treating theUAB clinical trials pave way to new cystic fibrosis drug UAB NewsPage 2 of 3The University of Alabama at BirminghamCystic fibrosis is caused by genetic errors in the CFTR genethat, among other problems, leads to persistent lunginfections. Recurring pulmonary infections result in theprogressive destruction of normal lung tissue and, eventually,the need for a double lung transplant, often in young, 20- to25-year-old individuals with cystic fibrosis.same group of patients. Rowe also thinks this new “corrector” combination will be better tolerated in patientsin the long run because of the less frequent pulmonary side effects.Cystic fibrosis is caused by genetic errors in the CFTR gene that, among other problems, leads to persistentlung infections. Recurring pulmonary infections result in the progressive destruction of normal lung tissue and,eventually, the need for a double lung transplant, often in young, 20- to 25-year-old individuals with cysticfibrosis.Details of the studyIn these recent Phase III trials, Vertex Pharmaceuticals examined the efficacy of this new combo drug in 24-week and eight-week studies using two patient groups: one that received the drug and one that received aplacebo. In both trials, the drug-treated group showed greater lung function improvement compared to theplacebo-treated group. Additionally, patients in the drug-treated group did not report more serious side effectsthan the placebo-treated patients.The first, 24-week EVOLVE studyassessed the combination treatment ofTezacaftor/Ivacaftor in patients with twodeltaF508 mutations, and it showed a 4.0percentage point baseline improvementof forced expiratory volume in thetreatment group compared to the placebogroup. The second, eight-week study,EXPAND, evaluated the treatment efficacy of the same combination drug and the monotherapy of Ivacaftor inpatients with one deltaF508 mutation and one residual CFTR ion channel function mutation. This shorter studyshowed a 6.8 percentage point improvement in the Tezacaftor/Ivacaftor combination therapy group and a 4.7percentage point improvement in the Ivacaftor monotherapy group compared to the placebo-treated group.While a 4.7 percentage point improvement might not sound like much, Rowe emphasized that EVOLVE studypatients with the residual function mutations showed this significant lung function improvement even after therelatively short, eight-week treatment. He believes the Tezacaftor/Ivacaftor combination will also be a greatcandidate for the next generation of cystic fibrosis drugs, mostly because this combination showed mildpulmonary side effects similar to the placebo’s side effects in these trials.Additionally, these trials are important since the EVOLVE study was the first Phase III clinical trial thatinvolved cystic fibrosis patients with residual function mutations. This means the new drug could be availableto another important population of CF patients.UAB clinical trials pave way to new cystic fibrosis drug UAB NewsPage 3 of 3The University of Alabama at BirminghamThe exact mechanism of how Tezacaftor works is not known yet. Patient recruitment for new clinical trialsinvestigating the mechanisms of action of Tezacaftor is underway, and a handful of cystic fibrosis patients havealready been enrolled in these studies at UAB.UAB, as part of the Cystic Fibrosis Foundation Therapeutics Development Network, plays a key role in thesenew developments in cystic fibrosis therapy. At UAB, Rowe holds the Nancy R. and Eugene C. GwaltneyFamily Endowed Chair in Medical Research, and Rowe is director of the Gregory Fleming James CysticFibrosis Research Center.The study was funded by Vertex Pharmaceuticals and supported by infrastructure awards by the NationalInstitutes of Health and the Cystic Fibrosis Foundation. The foundation helped develop cystic fibrosis drugswith Vertex through a collaborative agreement.

UAB clinical trials pave way to new cystic fibrosis drug

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UAB clinical trials pave way to new cystic fibrosis drug

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