Vertex Data Presented at European Cystic Fibrosis Society (ECFS) Conference Demonstrate Early and Long-Term Disease-Modifying Potential of Treating the Underlying Cause of CF

- Data from KALYDECO® (ivacaftor) studies show the potential to modify the long-term progression of the disease -

- Interim analysis of the ongoing extension study of tezacaftor/ivacaftor combination (approved in the U.S. as SYMDEKOTM) continues to demonstrate consistent safety and sustained benefits up to 48 weeks -

- Studies of investigational triple combination regimens highlight continued progress toward developing medicines to treat the underlying cause of the disease for up to 90 percent of people living with CF -

BELGRADE, Serbia I June 7, 2018 I Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced 10 scientific abstracts from the company’s portfolio of cystic fibrosis (CF) medicines are being presented at the 41stEuropean Cystic Fibrosis Conference taking place June 6-9, 2018, in Belgrade, Serbia. Collectively, the data support the potential disease-modifying benefits of treating the underlying cause of CF and Vertex’s progress toward enhancing and expanding treatment options for all people living with CF.

Data from the ongoing Phase 3, open-label ARRIVALstudy presented at an oral session and published online today in The Lancet Respiratory Medicine show that treatment with KALYDECO® (ivacaftor) resulted in substantial decreases in mean sweat chloride as well as improvements to multiple efficacy endpoints, suggesting the potential to preserve pancreatic function and modify the course of CF beginning in children as young as one year of age. In addition, final annual analyses of the completed, five-year, post-approval observational safety study of KALYDECO show that patients taking KALYDECO had lower risk of death, transplantation, hospitalization and pulmonary exacerbations compared to patients who were matched on age, gender and genotype class who did not receive KALYDECO. Together, these studies provide further support for the benefit of both early and long-term treatment with CFTR modulators.

Results from an interim analysis of the ongoing, 96-week EXTEND Phase 3 rollover study of tezacaftor/ivacaftor combination, approved in the U.S. as SYMDEKOTM (tezacaftor/ivacaftor and ivacaftor) also add to the growing body of evidence supporting the benefit of long-term treatment of the underlying cause of the disease. Analysis presented during a poster presentation shows that the initial improvements in lung function (measured by the absolute change in percent predicted forced expiratory volume in one second [ppFEV1]) observed in the Phase 3 EVOLVE study of patients homozygous for F508del were sustained for up to 48 weeks (24 weeks in EVOLVE + 24 weeks in EXTEND). Treatment was well-tolerated, demonstrating a safety profile consistent with that observed in the pivotal EVOLVE and EXPAND studies. Improvements across some secondary endpoints that were observed in the parent study were maintained in patients homozygous for F508del (n=459).

Previously announced data from Phase 1 and Phase 2 studies of three different next-generation correctors in combination regimens with tezacaftor and ivacaftor presented in an oral session highlight continued progress toward developing one medicine to treat up to 90 percent of people living with CF. These data demonstrate the potential to treat the underlying cause of CF in people who have one F508del mutation and one minimal function mutation not responsive to ivacaftor, tezacaftor or the combination of tezacaftor/ivacaftor, a severe and difficult-to-treat type of CF disease. With the goal of bringing the best regimen to people with CF, Vertex recently initiated Phase 3 studies evaluating two different triple combination regimens that contain a next-generation corrector (VX-445 or VX-659) in combination with tezacaftor and ivacaftor.

“The data presented at ECFS are further evidence that treating the cause of CF may significantly slow the progression of this disease beginning early in life, underscoring the importance of starting treatment for eligible patients as early as possible,” said Reshma Kewalramani, M.D., Executive Vice President and Chief Medical Officer at Vertex. “Over the past year, we’ve made rapid progress in developing multiple new medicines that treat the underlying cause of CF, and today, we are closer to our goal of developing medicines for all patients with CF than ever before.”

Presentation highlights include:

ARRIVAL Study: KALYDECO in Children Aged 12 to <24 months

“A phase 3, 2-part, single-arm study of ivacaftor treatment in patients < 2 years with a CFTR gating mutation: results from the ARRIVAL study in patients 1 to 2 years.” Oral presentation WS01.1 during Workshop WS01--Exciting News from CFTR Modulator Clinical Trials.

Results from the ongoing, open-label, Phase 3 ARRIVAL study of 25 children with CF aged 12 to <24 months who have one of 10 mutations in the CFTR gene (G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, G1349D or R117H) show treatment with KALYDECO for 24 weeks demonstrated a safety profile consistent with that observed in previous Phase 3 studies of older children and adults. Most adverse events were mild or moderate in severity, and no patient discontinued due to adverse events. The most common adverse events (≥30%) were cough (74%), pyrexia (37%), elevated aspartate aminotransferase (37%), elevated alanine aminotransferase (32%) and runny nose (32%). Serious adverse events were observed in two patients. Two patients had elevated liver enzymes greater than eight times the upper limit of normal, but continued to receive KALYDECO after a dose interruption.

Mean baseline sweat chloride for the children in this study was 104.1 mmol/L (n=14). Following 24 weeks of treatment with KALYDECO, the mean sweat chloride level was 33.8 mmol/L (n=14). In 10 subjects with paired sweat chloride samples at baseline and Week 24, there was a mean absolute change of -73.5 mmol/L. Sweat chloride is used as a tool to diagnose infants with CF, where levels greater than or equal to 60 mmol/L indicate that CF is likely, levels of 30-59 mmol/L indicate CF is possible and levels less than 30 indicate that CF is unlikely. In the study, 10 patients had greater than 40 mmol/L decreases in sweat chloride at week 24 and four of these patients had sweat chloride levels of less than 30 mmol/L at week 24. Improvements in multiple exploratory efficacy endpoints that measured exocrine pancreatic biomarkers, including levels of fecal elastase, serum immunoreactive trypsinogen (IRT), amylase and lipase levels, were also observed and suggest the potential for ivacaftor to protect against progressive exocrine pancreatic dysfunction when initiated at an early age.

These results supported submissions to the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) for KALYDECO in children aged 12 to <24 months.

KALYDECO Long-Term, Real-World Clinical Safety and Patient Outcomes

“Real-world outcomes in patients with cystic fibrosis treated with ivacaftor: 2016 US and UK cystic fibrosis Registry analyses.” Poster IPD2.02 during Session IPD2--What do We Learn from CFTR Modulator Use in Real Life.

“Disease progression in patients with cystic fibrosis treated with ivacaftor: analyses of real-world data from the US and UK cystic fibrosis Registries.” Poster IPD2.01 during Session IPD2.

Analyses of 2016 data from the fifth and final year of the completed, five-year, post-approval observational safety study of KALYDECO is the largest analyses of KALYDECO patients to date, and adds to the growing body of evidence showing that treating the underlying cause of CF has the potential to modify the course of disease in a real-world setting. In the U.S., data from 1,858 patients treated with KALYDECO show they had significantly lower risks of death, transplantation, hospitalizations and pulmonary exacerbations compared to matched untreated patients over the course of the fifth year of the study. In the U.K., data from 462 patients show similar trends. In both registries, the prevalence of the majority of evaluated CF complications and common bacterial pathogens tended to be lower in KALYDECO-treated patients.

Additional, longer-term analyses of patients who received KALYDECO for up to 5 years (635 patients in the U.S.) or up to 4 years (247 patients in the U.K.) show that patients on KALYDECO had consistently better preserved lung function, improved nutritional measures, reduced frequency of pulmonary exacerbations and hospitalizations and favorable trends in prevalence of CFRD and Pseudomonas aeruginosa compared to matched untreated patients. These findings were consistent with previous interim analyses. No new safety concerns were identified.

Additional Presentations

In addition to the studies noted above, other oral presentations accepted for ECFS include:

  • VOCAL: An interim analysis from an ongoing multinational (UK, Italy, Netherlands) observational study to assess real-world effectiveness of KALYDECO in patients with a non-G551D gating mutation (G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P or G1349D) was presented as an oral presentation and demonstrates sustained improvements in ppFEV1, pulmonary exacerbations and BMI over 12 months compared to the 12 month pre-KALYDECO period. The reduction in ppFEV1 rate of decline is further evidence that KALYDECO is a disease-modifying therapy for treating CF.
  • ORKAMBI® 2-5: Results from a Phase 3 study of ORKAMBI in children aged 2 to 5 years homozygous for the F508del mutation (n=60) were presented as an oral presentation and show treatment was generally safe and well tolerated for 24 weeks. The most common adverse event (≥30%) was cough (63%); most adverse events were mild or moderate in severity. Four patients experienced serious adverse events (2 pulmonary exacerbations, 1 gastroenteritis, 1 constipation) and three patients discontinued treatment due to treatment emergent adverse events or elevated liver function tests. Improvements were observed in secondary efficacy endpoints at week 24 as demonstrated by a mean decrease in sweat chloride of 31.7 mmol/L, improvements in growth parameters (BMI, weight, stature) and biomarkers of pancreatic function. These data supported the recent submission of regulatory applications for approval in the U.S. and EU.

About Cystic Fibrosis

Cystic fibrosis is a rare, life-shortening genetic disease affecting approximately 75,000 people in North America, Europe and Australia.

CF is caused by a defective or missing CFTR protein resulting from mutations in the CFTR gene. Children must inherit two defective CFTR genes — one from each parent — to have CF. There are approximately 2,000 known mutations in the CFTR gene. Some of these mutations, which can be determined by a genetic test, or genotyping test, lead to CF by creating non-working or too few CFTR proteins at the cell surface. The defective function or absence of CFTR protein results in poor flow of salt and water into and out of the cell in a number of organs. In the lungs, this leads to the buildup of abnormally thick, sticky mucus that can cause chronic lung infections and progressive lung damage in many patients that eventually leads to death. The median age of death is in the mid-to-late 20s.

About KALYDECO® (ivacaftor)

KALYDECO (ivacaftor) is the first medicine to treat the underlying cause of CF in people with specific mutations in the CFTR gene. Known as a CFTR potentiator, KALYDECO is an oral medicine designed to keep CFTR proteins at the cell surface open longer to improve the transport of salt and water across the cell membrane, which helps hydrate and clear mucus from the airways. KALYDECO is available as 150 mg tablets for adults and pediatric patients age 6 years and older, and is taken with fat-containing food. It is also available as 50 mg and 75 mg granules in pediatric patients ages 2 to less than 6 years and is administered with soft-food or liquid with fat-containing food.

People with CF who have specific mutations in the CFTR gene are currently benefiting from KALYDECO in 27 different countries across North America, Europe and Australia.

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. Patients with two copies of the F508del mutation are easily identified by a simple genetic test.

ORKAMBI is a combination of lumacaftor, which 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, and ivacaftor, which is designed to enhance the function of the CFTR protein once it reaches the cell surface. It is an oral pill taken every 12 hours - once in the morning and once in the evening.

About Vertex

Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious and life-threatening diseases. In addition to clinical development programs in CF, Vertex has more than a dozen ongoing research programs focused on the underlying mechanisms of other serious diseases.

Founded in 1989 in Cambridge, Mass., Vertex's headquarters is now located in Boston's Innovation District. Today, the company has research and development sites and commercial offices in the United States, Europe, Canada and Australia. Vertex is consistently recognized as one of the industry's top places to work, including being named to Science magazine's Top Employers in the life sciences ranking for seven years in a row. For additional information and the latest updates from the company, please visit

Collaborative History with Cystic Fibrosis Foundation Therapeutics, Inc. (CFFT)

Vertex initiated its CF research program in 2000 as part of a collaboration with CFFT, the nonprofit drug discovery and development affiliate of the Cystic Fibrosis Foundation. KALYDECO® (ivacaftor), ORKAMBI® (lumacaftor/ivacaftor), SYMDEKOTM (tezacaftor/ivacaftor and ivacaftor), VX-440, VX-152, VX-659 and VX-445 were discovered by Vertex as part of this collaboration.

SOURCE: Vertex Pharmaceuticals

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