Vertex Announces Significant Progress in Development Efforts to Treat Cause of Cystic Fibrosis in Most People With the Disease

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by Charles Moore |

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Vertex Pharmaceuticals Incorporated is a global biotechnology company whose corporate mission is to discover, develop and commercialize innovative medicines that can help people with serious diseases lead better lives. Vertex initiated its CF research program in 1998 as part of a collaboration with Cystic Fibrosis Foundation Therapeutics, Inc. (CFFT), the nonprofit drug discovery and development affiliate of the Cystic Fibrosis Foundation. Vertex’s Kalydeco and Orkambi CF drugs were discovered as part of this collaboration. However, in addition to the company’s main clinical development programs focused on cystic fibrosis, Vertex has more than a dozen ongoing research programs aimed at other serious and life-threatening diseases.

Vertex reports significant progress in its development efforts to treat the underlying cause of cystic fibrosis (CF) for the vast majority of people with the disease. The company has announced these progress updates to coincide with the 29th Annual North American Cystic Fibrosis Conference (NACFC),  currently being held October 7-10 at Phoenix, Arizona.


Vertex will webcast an investor presentation from the conference at approximately 6:15 p.m. MST (9:15 p.m. EDT) today Friday, October 9. A link to the webcast can be accessed through Vertex’s website at in the “Investors” section under “Events and Presentations.” To ensure a timely connection, it is recommended that users register at least 15 minutes prior to the scheduled webcast. An archived webcast will be available on the company’s website.

Cystic fibrosis (CF) a rare, life-threatening genetic disease affecting approximately 75,000 people in North America, Europe and Australia, is caused by caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that encodes CFTR, a chloride channel that regulates the movement of salt and water into and out of cells in organs such as the lungs, pancreas and gastrointestinal tract. 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, lead to CF by creating defective or too few CFTR proteins at the cell surface. The defective or missing CFTR protein results in poor flow of salt and water into or out of the cell in a number of organs, including the lungs. This leads to the buildup of abnormally thick, sticky mucus that is very difficult to clear, blocks the airways and the glands, and creates an environment where bacteria can easily grow, often resulting in chronic lung infections and progressive lung damage that eventually leads to death. The median predicted age of survival for a person born today with CF is 41 years, but the median age of death is 27 years. More than 90 percent of all CF patients die of respiratory failure.

Efficacy and Safety of Lumacaftor/Ivacaftor Combination Therapy in Patients With CF Homozygous for F508del-CFTR by FEV1 Subgroups

ChodakewitzJ“With continued expansion in the number of people eligible for Kalydeco, the recent FDA approval of Orkambi in the U.S. and the advancement of two next-generation correctors into clinical development, we are making significant progress toward our goal of treating the vast majority of people with CF,” says Jeffrey Chodakewitz, M.D., Executive Vice President and Chief Medical Officer at Vertex in a release. “We are conducting studies with our investigational combination regimens in groups of CF patients with mutations that represent approximately 90 percent of all people with CF. While there is much work still to be done, we believe we are on the right path to further enhance the treatment of CF in the years ahead.”

29th Annual North American Cystic Fibrosis Conference Vertex Presentation Abstracts

More than 15 abstracts related to Vertex’s CF development program have been accepted for presentation at NACFC — Vertex having provided the following updates to its development program in CF and highlighted select presentations from the conference:

Two Next-Generation Correctors To Enter Clinical Development

Vertex is advancing two next-generation correctors from its research program into clinical development, known as VX-152 and VX-440. These next-generation correctors will be evaluated alone and in combination with VX-661/ivacaftor in Phase 1 studies in healthy volunteers beginning in November 2015. Pending results of these studies, Vertex plans to initiate Phase 2 studies in people with CF evaluating VX-440 or VX-152 in combination with VX-661/ivacaftor in the second half of 2016.

Studies of a triple combination (VX-152/VX-661/ivacaftor and VX-440/VX-661/ivacaftor) planned for the second half of 2016 are expected to enroll people with CF who have two copies of the F508del mutation and people who have one copy of the F508del mutation and a second mutation that results in minimal CFTR function. VX-152 and VX-440 are designed to further improve processing and trafficking of the CFTR protein to the cell surface, beyond that observed with a single corrector combined with ivacaftor, which may enable increased CFTR chloride transport, a measure of the function of the CFTR protein at the cell surface.

KALYDECO (ivacaftor)

On October 7, Vertex announced its supplemental New Drug Application for the use of KALYDECO in people ages two and older with one of 23 residual function mutations has been accepted for review by the FDA. The FDA granted Vertex’s request for Priority Review of this sNDA, and a target review date of February 6, 2016 was set under the Prescription Drug User Fee Act (PDUFA) for the FDA’s decision on the sNDA. More than 1,500 people with CF in the U.S. have the mutations represented in the sNDA.

Additionally, since CF-related complications can emerge early in life, Vertex plans to conduct a clinical study of KALYDECO in children less than two years of age to evaluate the effect of KALYDECO on markers of CF disease in young children. The study will utilize a weight-based dose of KALYDECO granules that can be mixed in soft foods or liquids. The study is expected to begin in the first quarter of 2016. On September 25, Vertex announced that the EU Committee for Medicinal Products for Human Use (CHMP) issued positive opinions recommending KALYDECO for use in children ages 2 to 5 with CF who have one of nine gating mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and in people with CF ages 18 and older who have the R117H mutation.

Long-Term Safety Data of Ivacaftor Treatment

Interim data from an ongoing 5-year observational study evaluating the long-term outcomes in people treated with ivacaftor will be presented at NACFC for the first time. In this analysis, which is based on data from the 2013 CF Foundation Patient Registry, 999 patients were treated with ivacaftor for an average duration of treatment of 1.4 years. As of 2013, the annual risk of death, organ transplantation, hospitalization due to any reason and frequency of pulmonary exacerbations were all significantly lower in the ivacaftor group compared to matched controls from the CF Foundation Patient Registry. No CF-related complications were significantly more common in the ivacaftor group. These data will be presented as part of a poster titled Ivacaftor Long-term Safety Study: Analysis of 2013 US CF Foundation Patient Registry Data.

Data will also be presented as part of a poster titled Improved Rate of Decline in Percent Predicted FEV1 is Not Associated With Acute Improvement in Percent Predicted FEV1 in Patients With Cystic Fibrosis Treated With Ivacaftor that will be discussed as part of Poster Discussion/Workshop Session 24, New Therapies.

Changes in Height with Ivacaftor Treatment

A post-hoc analysis of the ENVISON study of ivacaftor in children ages 6 to 11 years with the G551D mutation evaluated the effect of ivacaftor on linear growth (height) and other growth measures and will be presented at NACFC for the first time. The results showed that ivacaftor treatment resulted in an improvement in multiple growth parameters, including linear growth, in children with CF.

Positive Opinion from EU CHMP for ORKAMBI

On September 25, Vertex announced that the EU CHMP issued a positive opinion recommending ORKAMBI for use in people ages 12 and older with two copies of the F508del mutation. In Europe, approximately 12,000 people with CF ages 12 and older have two copies of this mutation.

Ongoing Phase 3 Studies in Children Ages 6 to 11

Vertex is currently conducting two Phase 3 clinical studies of lumacaftor/ivacaftor in children 6 to 11 years of age. The first study is evaluating lumacaftor/ivacaftor in approximately 50 children to support the potential FDA approval in children ages 6 to 11. The primary endpoint of this six-month study is safety. Vertex plans to submit an sNDA to the FDA in the first half of 2016, pending data from this study.

Correlation of Pulmonary Exacerbations with Acute Improvements in Lung Function in TRAFFIC and TRANSPORT Studies

Data from a post-hoc analysis evaluating the correlation of acute lung function improvements to reductions in pulmonary exacerbations in the Phase 3 TRAFFIC and TRANSPORT studies showed that treatment with lumacaftor/ivacaftor resulted in a reduction in the frequency of pulmonary exacerbations regardless of the acute improvement in lung function at Day 15 in the study. These data will be presented for the first time at NACFC in a poster titled Association Between Changes in Percent Predicted FEV1 and Incidence of Pulmonary Exacerbations, Including Those Requiring Hospitalization and/or IV Antibiotics, in Patients With CF Treated With Lumacaftor in Combination With Ivacaftor.

Efficacy and Safety of Lumacaftor/Ivacaftor Across Sub-Groups in TRAFFIC and TRANSPORT Studies

A pre-specified pooled analysis that evaluated whether baseline lung function was predictive of the efficacy and safety of lumacaftor/ivacaftor treatment will be presented at NACFC for the first time. In this analysis, patients were stratified based on their screening and study baseline lung function values. The results showed that the efficacy and safety of lumacaftor/ivacaftor were generally similar across lung function subgroups. These data will be presented as part of a poster titled Efficacy and Safety of Lumacaftor/Ivacaftor Combination Therapy in Patients With CF Homozygous for F508del-CFTR by FEV1 Subgroups.

VX-661 in Combination with Ivacaftor

Four Phase 3 studies of the investigational combination of VX-661 and ivacaftor are ongoing in multiple different groups of people with CF who have at least one copy of the F508del mutation. The studies are evaluating VX-661 dosed as 100 mg once daily (QD) in combination with ivacaftor dosed as 150 mg every 12 hours (q12h).

Studies of the ENaC Inhibitor VX-371

In June 2015, Vertex and Parion Sciences entered into a collaboration to develop investigational epithelial sodium channel (ENaC) inhibitors for the potential treatment of cystic fibrosis (CF) and other pulmonary diseases. Parion is currently conducting an exploratory Phase 2a study (known as the CLEAN-CF study) of inhaled VX-371 (P-1037), compared to treatment with VX-371 with hypertonic saline, in approximately 120 people with CF. The study is enrolling people with a confirmed diagnosis of CF and any CFTR mutation. Additionally, Vertex plans to conduct a placebo-controlled Phase 2a study to evaluate VX-371 in patients taking lumacaftor/ivacaftor, both with and without the addition of hypertonic saline, who have two copies of the F508del mutation. This Phase 2a study is expected to begin in early 2016.

29th Annual North American Cystic Fibrosis Conference (NACFC)

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