Vertex to Present Data Demonstrating Benefits of Long-Term and Early Treatment With CFTR Modulators at the European Cystic Fibrosis Conference

• KAFTRIO^®(ivacaftor/tezacaftor/elexacaftor) in a combination regimen with ivacaftor real-world safety and effectiveness interim results show improved lung function and reductions in risk of pulmonary exacerbations, lung transplant and death for people with cystic fibrosis (CF) -

• Study in people with CF (F/F or F/MF genotypes) treated with KAFTRIO^® in a combination regimen with ivacaftor shows no mean loss of lung function after two years compared to those not treated with a CFTR modulator -

• Long-term real-world study results show benefits of initiating KALYDECO^® (ivacaftor) at young age -

LONDON – June 10, 2022 – Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that five scientific abstracts on the company’s portfolio of cystic fibrosis (CF) medicines will be presented at the European Cystic Fibrosis Society's (ECFS) 45th European Cystic Fibrosis Conference held June 8-11, 2022, in Rotterdam, the Netherlands.

Vertex will present the first analysis of data collected in the U.S. CF Foundation Patient Registry (CFFPR) of over 16,000 people with CF treated with KAFTRIO^® (ivacaftor/tezacaftor/elexacaftor) in combination with ivacaftor for an average of nine months. This first interim analysis of an ongoing five-year post-authorization study (abstract WS22.05) showed that real-world treatment with KAFTRIO^® in combination with ivacaftor was associated with improved lung function and a 77% reduced risk of pulmonary exacerbations compared to pre-KAFTRIO^® in combination with ivacaftor baseline, as well as an 87% lower risk of lung transplant and a 74% lower risk of death, compared to the historical 2019 U.S. CFFPR population. No new safety concerns were identified.

Vertex will also present data comparing the annual rate of lung function change in people with CF ages 12 years and older with two F508del mutations (F/F) or one F508del mutation and one minimal function mutation (F/MF) treated with KAFTRIO^® in combination with ivacaftor in pivotal studies and an open-label extension study compared to propensity-score matched historical CFTR-modulator-untreated controls from the U.S. CFFPR (abstract WS22.04). Results show that KAFTRIO^® in combination with ivacaftor demonstrated on average no decrease in ppFEV₁ over a two-year period in this population, in contrast to declines seen in the matched controls. The analysis indicates that treatment with KAFTRIO^® in combination with ivacaftor has the potential to have an impact on the trajectory of CF lung disease.

Additionally, Vertex will present data from a long-term real-world study demonstrating that initiating KALYDECO^® (ivacaftor) early in life (ages 6-10 years) preserves lung function to a greater extent than if KALYDECO^® is initiated at an older age (abstract WS17.03). These results show the importance of early initiation of KALYDECO^® for eligible patients.

“These long-term and real-world studies show the potentially transformative benefits of treatment with CFTR modulators and add to the substantial body of evidence supporting treatment as early in life as possible,” said Carmen Bozic, M.D., Executive Vice President, Global Medicines Development and Medical Affairs, and Chief Medical Officer at Vertex. “We continue to make rapid progress in developing medicines that treat the underlying cause of CF, and today, we are closer to our goal of developing highly effective therapies for all patients with CF than ever before.”

Additional Presentations

In addition to the studies noted above, other Vertex presentations at the conference this year support the long-term and early use of CFTR modulators:

• Abstract WS08.04 — Results of real-world study in people with CF with select residual function mutations, treated with KALYDECO^® (ivacaftor)
• Abstract WS17.02 — Results from an ORKAMBI^® (lumacaftor/ivacaftor) exploratory phase 2 open-label extension study in children with CF ages 2-5

About Cystic Fibrosis

Cystic fibrosis (CF) is a rare, life-shortening genetic disease affecting more than 83,000 people globally. CF is a progressive, multi-organ disease that affects the lungs, liver, pancreas, GI tract, sinuses, sweat glands and reproductive tract. CF is caused by a defective and/or missing CFTR protein resulting from certain mutations in the CFTR gene. Children must inherit two defective CFTR genes — one from each parent — to have CF, and these mutations can be identified by a genetic test. While there are many different types of CFTR mutations that can cause the disease, the vast majority of people with CF have at least one F508del mutation. CFTR mutations lead to CF by causing the CFTR protein to be defective or by leading to a shortage or absence of CFTR protein at the cell surface. The defective function and/or absence of CFTR protein results in poor flow of salt and water into and out of the cells in a number of organs. In the lungs, this leads to the buildup of abnormally thick, sticky mucus, chronic lung infections and progressive lung damage that eventually leads to death for many patients. The median age of death is in the early 30s.

About KAFTRIO^® (ivacaftor/tezacaftor/elexacaftor) in Combination With Ivacaftor 

In people with certain types of mutations in the CFTR gene, the CFTR protein is not processed or folded normally within the cell, and this can prevent the CFTR protein from reaching the cell surface and functioning properly. KAFTRIO^® (ivacaftor/tezacaftor/elexacaftor) in combination with ivacaftor is an oral medicine designed to increase the quantity and function of the CFTR protein at the cell surface. Elexacaftor and tezacaftor work together to increase the amount of mature protein at the cell surface by binding to different sites on the CFTR protein. Ivacaftor, which is known as a CFTR potentiator, is designed to facilitate the ability of CFTR proteins to transport salt and water across the cell membrane. The combined actions of ivacaftor, tezacaftor and elexacaftor help hydrate and clear mucus from the airways. 

KAFTRIO^® in combination with ivacaftor is approved in the European Union for the treatment of cystic fibrosis (CF) in patients aged 6 years and older who have at least one copy of the F508del mutation in the CFTR gene.  

For complete product information, please see the Summary of Product Characteristics that can be found on www.ema.europa.eu. 

About KALYDECO^® (ivacaftor)

In people with certain types of mutations in the CFTR gene, the CFTR protein at the cell surface does not function properly. Known as a CFTR potentiator, ivacaftor is an oral medicine designed to facilitate the ability of CFTR proteins to transport salt and water across the cell membrane, which helps hydrate and clear mucus from the airways. KALYDECO^® (ivacaftor) was the first medicine to treat the underlying cause of cystic fibrosis (CF) in people with specific mutations in the CFTR gene.

KALYDECO^® is approved in the European Union for the treatment of cystic fibrosis (CF) in patients ages 4 months and older who have an R117H mutation or one of the following gating (class III) mutations in the CFTR gene: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N or S549R.

For complete product information, please see the Summary of Product Characteristics that can be found on www.ema.europa.eu. 

About ORKAMBI^® (lumacaftor/ivacaftor)

In people with two copies of the F508del mutation, the CFTR protein is not processed and trafficked normally within the cell, resulting in little to no CFTR protein at the cell surface.

ORKAMBI^® (lumacaftor/ivacaftor) is an oral medicine that is a combination of lumacaftor and ivacaftor. Lumacaftor is designed to increase the amount of mature protein at the cell surface by targeting the processing and trafficking defect of the F508del-CFTR protein. Ivacaftor, which is known as a CFTR potentiator, is designed to facilitate the ability of CFTR proteins to transport salt and water across the cell membrane. The combined actions of lumacaftor and ivacaftor help hydrate and clear mucus from the airways.

ORKAMBI^® is approved in the European Union for the treatment of cystic fibrosis (CF) in patients aged 2 years and older who have two copies of the F508del mutation in the CFTR gene.

For complete product information, please see the Summary of Product Characteristics that can be found on www.ema.europa.eu. 

About Vertex

Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases. The company has multiple approved medicines that treat the underlying cause of cystic fibrosis (CF) — a rare, life-threatening genetic disease — and has several ongoing clinical and research programs in CF. Beyond CF, Vertex has a robust pipeline of investigational small molecule, cell and genetic therapies in other serious diseases where it has deep insight into causal human biology, including sickle cell disease, beta thalassemia, APOL1-mediated kidney disease, pain, type 1 diabetes, alpha-1 antitrypsin deficiency and Duchenne muscular dystrophy. 

Founded in 1989 in Cambridge, Mass., Vertex's global headquarters is now located in Boston's Innovation District and its international headquarters is in London. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia and Latin America. Vertex is consistently recognized as one of the industry's top places to work, including 12 consecutive years on Science magazine's Top Employers list and one of the 2021 Seramount (formerly Working Mother Media) 100 Best Companies. For company updates and to learn more about Vertex's history of innovation, visit global.vrtx.com or follow us on Twitter and LinkedIn.

Special Note Regarding Forward-Looking Statements

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements made by Dr. Bozic in this press release, statements regarding the potential benefits, safety and efficacy of our products, and our plans to present data about our portfolio of CF products at the ECFS European Cystic Fibrosis Conference, including an analysis of data from the ongoing five-year post-authorization safety study for KAFTRIO^® in combination with ivacaftor, data comparing the annual rate of lung function change in certain individuals with CF and our assessment of the impact of such data, data regarding the early initiation of KALYDECO^® and our assessment of the impact of such data, and additional scientific presentations regarding our marketed CF products, including expectations regarding the abstracts that will be made available at the ECFS European Cystic Fibrosis Conference. While Vertex believes the forward-looking statements contained in this press release are accurate, these forward-looking statements represent the company's beliefs only as of the date of this press release and there are a number of risks and uncertainties that could cause actual events or results to differ materially from those expressed or implied by such forward-looking statements. Those risks and uncertainties include, among other things, that data from the company's development programs may not support registration, approval or further development of its compounds due to safety, efficacy or other reasons, risks related to approval and commercialization of our medicines, and other risks listed under the heading “Risk Factors” in Vertex's most recent annual report and subsequent quarterly reports filed with the Securities and Exchange Commission (SEC) and available through the company's website at global.vrtx.com and on the SEC’s website at www.sec.gov. You should not place undue reliance on these statements or the scientific data presented. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.

(VRTX-GEN)