Category: CF Community

SOURCE – VERTEX OFFICIAL PRESS RELEASE

 

November 5, 2014

Vertex Submits Applications in the U.S. and Europe for Approval of Lumacaftor in Combination with Ivacaftor for People with Cystic Fibrosis Who Have Two Copies of the F508del Mutation

-U.S. submission includes request for Priority Review; Accelerated Assessment has been granted in the EU-

-Approximately 8,500 people in the U.S. and 12,000 in Europe ages 12 and older have two copies of the F508del mutation-

BOSTON–(BUSINESS WIRE)– Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) and a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for a fully co-formulated combination of lumacaftor (400mg q12h) and ivacaftor (250mg q12h) for people with cystic fibrosis (CF) ages 12 and older who have two copies of the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. There are approximately 22,000 people with CF ages 12 and older who have two copies of the F508del mutation in North America, Europe and Australia, including approximately 8,500 in the United States and 12,000 in Europe.

“The combination of lumacaftor and ivacaftor is the first potential treatment designed to target the underlying cause of cystic fibrosis in people with two copies of the F508del mutation, which is the most common form of the disease,” said Jeffrey Chodakewitz, M.D., Executive Vice President and Chief Medical Officer at Vertex. “Today’s submissions represent important progress toward our ongoing efforts to develop new medicines for the vast majority of people with cystic fibrosis, and we look forward to working closely with regulatory agencies to bring this treatment to eligible patients as quickly as possible.”

In the U.S., the combination of lumacaftor and ivacaftor received Breakthrough Therapy Designation in late 2012. The U.S. submission includes a request for Priority Review, which, if granted, would shorten the FDA’s anticipated review time from approximately 12 to 8 months. The European Committee for Medicinal Products for Human Use (CHMP) has granted Vertex’s request for Accelerated Assessment of the MAA, which is given to new medicines of major public health interest and shortens the review time from approximately 210 to 150 days for the CHMP to give an opinion following the start of the review. The CHMP opinion is then reviewed by the European Commission, which generally issues a final decision within three months. If approved, Vertex would then begin the country-by-country reimbursement approval process. Both applications seek approval for a fully co-formulated combination treatment dosed as two tablets every 12 hours (four tablets daily).

The NDA and MAA submissions are based on previously announced data from two global Phase 3 studies, TRAFFIC and TRANSPORT, and the first interim data from the subsequent rollover study in people ages 12 and older who have two copies of the F508del mutation treated with standard-of-care medicines. The TRAFFIC and TRANSPORT studies showed improvements in lung function and other measures of disease, such as pulmonary exacerbations, through 24 weeks of treatment with lumacaftor in combination with ivacaftor. Initial interim data from the rollover study showed that lung function improvements were sustained for 48 total weeks of treatment (24 weeks in TRAFFIC/TRANSPORT + 24 weeks in rollover study). The combination was generally well tolerated in all three studies. In TRAFFIC and TRANSPORT, the most common adverse events were infective pulmonary exacerbation, cough, headache and increased sputum.

Cystic fibrosis is a rare genetic disease for which there is no cure. It is caused by a defective or missing CFTR protein resulting from mutations in the CFTR gene. The defective or missing protein results in poor flow of salt and water into and out of the cell in a number of organs, including the lungs. 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. Lumacaftor, a CFTR corrector, is designed to address the processing and trafficking defect of the F508del-CFTR protein, increasing the amount of functional protein at the cell surface where ivacaftor, a CFTR potentiator, can further enhance its function.

Expanded Access Programs

In recognition of the immediate needs of some people with CF, Vertex is working to make the combination of lumacaftor and ivacaftor available to people ages 12 and older who have two copies of the F508del mutation, are in critical medical need and meet additional eligibility criteria. In the U.S., Vertex plans to begin a Phase 3b study for a limited number of people who have severe lung disease in the first quarter of 2015, followed by an expanded access program in the second quarter of the year, pending discussions with the FDA. Vertex will also work with regulatory authorities outside the United Statestoward implementing additional expanded access programs in other countries, with a goal of opening programs for eligible patients in the second quarter of 2015.

For more information, please contact Vertex Medical Information (U.S.: 1-877-634-8789 or medicalinfo@vrtx.com; outside the U.S.:vertexmedicalinfo@vrtx.com).

About the Combination

The combination of lumacaftor and ivacaftor is the first potential medicine designed to treat the underlying cause of CF in people with two copies of the F508del mutation, the most common form of the disease. In North America, Europe and Australia, there are approximately 22,000 people ages 12 and older who have two copies of the F508del mutation.

Known as a CFTR corrector, lumacaftor aims to address the processing and trafficking defect of the F508del-CFTR protein to enable it to reach the cell surface where the CFTR potentiator, ivacaftor, can further enhance the ion channel function of the CFTR protein. Ivacaftor is designed to help the CFTR channel at the cell surface open more often to improve the transport of salt and water across the cells. In combination, lumacaftor and ivacaftor are believed to help hydrate and clear mucus from the airways.

About Cystic Fibrosis

Cystic fibrosis is a rare, life-threatening genetic disease affecting approximately 75,000 people in North America, Europe and Australia. Today, the median predicted age of survival for a person with CF is between 34 and 47 years, but the median age of death remains in the mid-20s.

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 more than 1,900 known mutations in the CFTR gene. Some of these mutations, which can be determined by a genetic, or genotyping test, lead to CF by creating non-working or too few CFTR protein at the cell surface. The defective or missing CFTR protein results in poor flow of salt and water into and out of the cell in a number of organs, including the lungs. This leads to the buildup of abnormally thick, sticky mucus that can cause chronic lung infections and progressive lung damage.

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

Vertex initiated its CF research program in 1998 as part of a collaboration with CFFT, the nonprofit drug discovery and development affiliate of the Cystic Fibrosis Foundation. This collaboration was expanded to support the accelerated discovery and development of Vertex’s CFTR modulators.

About Vertex

Vertex is a global biotechnology company that aims to discover, develop and commercialize innovative medicines so people with serious diseases can lead better lives. In addition to our clinical development programs focused on cystic fibrosis, Vertex has more than a dozen ongoing research programs aimed at other serious and life-threatening diseases.

Founded in 1989 in Cambridge, Mass., Vertex today has research and development sites and commercial offices in the United States, Europe, Canada andAustralia. For five years in a row, Science magazine has named Vertex one of its Top Employers in the life sciences. For additional information and the latest updates from the company, please visit www.vrtx.com.

Special Note Regarding Forward-looking Statements

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including, without limitation, Dr. Chodakewitz’s statements in the second paragraph of the press release, and the information provided regarding (i) Vertex’s NDA submission to the FDA and MAA submission to the EMA, (ii) Vertex’s request for priority review and (iii) Vertex’s planned compassionate use program and Phase 3b study. 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 factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, that regulatory authorities may not approve, or approve on a timely basis, lumacaftor in combination with ivacaftor due to safety, efficacy or other reasons, and other risks listed under Risk Factors in Vertex’s annual report and quarterly reports filed with the Securities and Exchange Commission and available through the company’s website at www.vrtx.com. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.

(VRTX-GEN)

Vertex Pharmaceuticals Incorporated

Investors:
Michael Partridge, 617-341-6108
or
Kelly Lewis, 617-961-7530
or
Media: mediainfo@vrtx.com
U.S.: Zach Barber, 617-341-6992
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Europe: Megan Goulart, +41 22 593 6066

Source: Vertex Pharmaceuticals Incorporated

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SOURCE – VERTEX OFFICIAL PRESS RELEASE

SOURCE – Marketwatch.com

PRESS RELEASE
April 17, 2014, 7:31 a.m. EDT
Alcresta Announces Agreement with Cystic Fibrosis Foundation Therapeutics to Develop Point-of-Care Nutritional Products
Agreement Highlights Importance of Medical Nutrition in Managing Cystic Fibrosis

NEWTON, Mass., Apr 17, 2014 (BUSINESS WIRE) — Alcresta®, a leading medical nutrition company developing innovative enzyme-based products for individuals with unique nutritional needs battling acute conditions or chronic diseases, today announced the company has signed an agreement with Cystic Fibrosis Foundation Therapeutics (CFFT) to accelerate the development of Alcresta’s enzyme-based point-of-care products to support the nutritional status of people with cystic fibrosis (CF). CFFT is the nonprofit drug discovery and development affiliate of the Cystic Fibrosis Foundation.

More than 90 percent of people with CF have a compromised pancreas and need enzyme-based nutritional products to digest and absorb vitamins and nutrients. To address these challenges, people with compromised pancreatic or gastrointestinal function, including people with CF, consume nutritional drinks and use tube feedings to supplement their diet. This agreement allows Alcresta to accelerate the development of its nutrition technology and advance point-of-care products designed to address the specific needs of the CF population and others with unique nutritional needs by improving absorption of beneficial fatty acids and aiding in overall caloric intake.

According to the CF Foundation’s patient data report, a relationship has been established in CF between good health outcomes and patients’ nutritional levels, reinforcing the need for individuals to maintain adequate weight gain (BMI). Specifically, malabsorption of fats may contribute to the inflammatory characteristics of CF, and negatively affect a person’s ability to maintain or gain weight.

“This agreement continues to validate Alcresta’s technology and will allow us to speed up the development of our point-of-care portfolio of products that we believe will improve the overall well-being of people with CF and others with specific nutritional needs,” said Robert Gallotto, co-founder and president of Alcresta. “We believe science-based nutrition can lead to improved care, and we look forward to working with the CF Foundation to help make a meaningful difference for people in need of improved nutrition.”

Alcresta’s lead program is an enzyme-based point-of-care product focused on improving the digestion and enabling proper absorption of fats, including critically important “good fats” – in particular omega-3 fatty acids like docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). The initial product offering is designed to mimic the function of pancreatic lipase by pre-hydrolyzing fats in liquid nutritional products and tube feeding formulas to fatty acids and mono-glycerides prior to consumption in individuals who require special nutritional care where there is a known relationship between proper nutrition, caloric intake and weight maintenance.

About the Cystic Fibrosis Foundation

The Cystic Fibrosis Foundation is the world’s leader in the search for a cure for cystic fibrosis. The Foundation funds more CF research than any other organization, and nearly every CF drug available today was made possible because of Foundation support. We are a nonprofit donor-supported organization dedicated to attacking cystic fibrosis from every angle. Our focus is to support the development of new drugs to fight the disease, improve the quality of life for those with CF, and ultimately to find a cure. Based in Bethesda, Md., the Foundation funds and accredits a national care center network that has been recognized by the National Institutes of Health as a model of care for a chronic disease. For more information, visit http://www.cff.org .

About Alcresta

Alcresta is a leading medical nutrition company developing and commercializing innovative enzyme-based point-of-care products to improve the digestion and absorption of key nutrients to support growth, development and nutrition in people battling acute conditions or chronic diseases. The demand for high-value nutritional products is increasing, driving the growth of a $40 billion global market. While there have been important recent advances in nutritional drinks and products, there remains a significant need for enzyme-based nutritional products that support healthier living, maximize nutrient and caloric absorption, and complement conventional medical care. Leveraging its existing proprietary platform of point-of-care nutritional products, Alcresta has developed a lead product designed to improve the digestion and absorption of fats, in particular long-chain polyunsaturated fatty acids like omega-3 (including DHA, EPA). The importance of long-chain polyunsaturated fatty acids like omega-3 is well documented across the full spectrum of patient care from infants to adults and individuals battling acute conditions or chronic diseases. The company’s platform is supported by the Alcresta team’s extensive experience in pharmaceutical and nutritional product development. Based in Newton, Mass., the company is backed by top-tier venture investors Bessemer Venture Partners, Frazier Healthcare and Third Rock Ventures. For more information, please visit http://www.alcresta.com .

SOURCE: Alcresta

SOURCE

[Posted by Mike Nace on bionews-tx.com]

Israel-based Kamada Ltd., a drug development company currently developing plasma-derived protein therapeutics that are chiefly targeting orphan diseases, indicated recently in a press release that their lead drug candidate Alpha-1 Antitrypsin (AAT), which is currently in trials for treatment of Alpha-1 Antitrypsin Deficiency (AATD, or Inherited Emphysema), will also be tested in a new round of clinical trials for cystic fibrosis this summer.

The news comes as part of a larger news release of the launch of the AAT trial for AATD, which will feature a double-blind, placebo-controlled study evaluating the safety and efficacy of AAT by inhalation. Kamada concludes its news release by stating that the company plans to initiate a U.S. phase 2 clinical trial of its inhaled AAT to treat Cystic Fibrosis in the second half of 2014.

Detailed information about the upcoming U.S. Phase 2 clinical trial for AAT in treatment of cystic fibrosis is not immediately available. However, the company has had previous success in researching and developingcystic fibrosis treatments, including Bramitob, which features Tobramycin as its active ingredient and offers “management of chronic pulmonary infection due to Pseudomonas aeruginosa in patients of 6 years and older with cystic fibrosis,” according to the company’s website.

In addition, AAT has been given the status of an Orphan Drug to treat cystic fibrosisboth in the United states in Europe. According to information fromClinicalTrials.gov, a “completed phase II study with CF patients  showed high safety and tolerability profile sided to demonstration of significant decrease in lung inflammation which was reflected, among others in the drop of neutrophil elastase enzyme in the lungs of the CF patients, an enzyme that has a major affect in lung inflammation and disease progression as a result.” This study, which was completed in 2009, led to Kamada winning an IND (Investigational New Drug) approval from the FDA, for a phase II clinical trial in the US for the treatment of CF.

For now, Kamada will continue to develop AAT for the AATD indication. David Tsur, Co-founder and CEO of Kamada commented, “We are very excited to initiate this U.S. study of our inhaled AAT to treat AATD, which represents a potentially revolutionary, user-friendly, convenient and efficient treatment compared with the current AAT treatment that requires weekly invasive, intravenous infusions. The U.S. market offers a significant opportunity to bring an inhaled therapy to patients suffering from this genetic lung disease, not merely as a more user friendly treatment, but also because the targeted delivery and treatment rationale directly to the lung are expected to enhance efficacy. Initiating this U.S. clinical study is an important step in our global strategy to commercialize our novel, inhaled human AAT.”

SOURCE

SOURCE: CFF.org 

Cystic Fibrosis Foundation Therapeutics, Inc. (CFFT), an affiliate of the Cystic Fibrosis Foundation, announced it will extend funding for continued collaboration with Proteostasis Therapeutics, Inc., for the development of new therapies to treat the most common CF mutation, Delta F508.

Proteostasis will continue to focus its research and development on small molecules that correct defective CFTR protein in the cell and allow it to function properly.

In the Delta F508 mutation, the defective protein CFTR does not move to its proper place at the cell surface, impeding the flow of fluids into the airways. Nearly 90 percent of people with CF have at least one copy of the Delta F508 mutation.

In addition to this collaboration, CFFT is investing in a robust pipeline of potential therapies that target CF from every angle, including research collaborations with Pfizer, Genzyme and Vertex to accelerate the discovery and development of new drugs.

CFFT’s and the Foundation’s goal is to find effective therapies and a cure for 100 percent of people with the disease.

Proteostasis Therapeutics develops disease-modifying therapeutics for orphan and neurodegenerative diseases.

SOURCE: CFF.org 

Source: Science Daily (July 31, 2012)

Cystic fibrosis is an inherited disease caused by mutations in a gene that adversely affect its protein product. In its correct form and cellular location, this protein, cystic fibrosis transmembrane conductance regulator (CFTR), functions as a channel for ions to move across cell membranes, and is critical for maintaining cellular salt and water balance.

The most common CF-causing genetic mutation, known as delta F508, disrupts the process whereby the CFTR protein is folded into its correct shape and shipped to the membranes of cells that line the airways and other organs. Most of the defective CFTR protein is misprocessed and gets degraded. The lack of normal CFTR ion channels leads to numerous problems, including lung infection and inflammation, the major causes of disease and death in cystic fibrosis.

Despite its importance, how the CFTR protein is made and delivered to cell membranes in its functioning form is not well understood. The UI team led by Paul McCray, M.D., professor of pediatrics and microbiology with UI Health Care and the Roy J. Carver Chair in Pulmonary Research and Vice Chair for Research in Pediatrics, investigated the role of microRNAs — small non-coding stretches of RNA — in regulating expression of CFTR.

In their research, McCray and colleagues discovered that one particular microRNA, called miR-138, helps control the biosynthesis of CFTR by regulating a network of genes involved in the production and processing of the protein. The study, published online the week of July 30 in the Proceedings of the National Academy of Sciences (PNAS) Early Edition, shows that that miR-138 acts on the other genes to orchestrate a cellular program that increases production of CFTR and increases the amount of the protein that is transported to the cell membrane where it functions as an ion channel.

“We first wanted to determine how this gene network impacts the CFTR protein produced in people who don’t have cystic fibrosis,” says lead author Shyam Ramachandran, Ph.D.. “We identified a novel regulatory circuit, but then asked ourselves if any of this affected the mutant protein.”

Surprisingly, the researchers found that when the gene network was activated by miR-138, it not only increased the amount of the mutated protein, but also partially restored the protein’s function.

By manipulating the microRNA network, the UI team was able to change the fate of the misfolded CFTR from being degraded in the cell to functioning as an ion channel in the cell membrane.

“This was a very surprising finding,” Ramachandran says. “It unexpectedly helps rescue the function of the mutant protein.”

Because most people with CF have one or two copies of the delta F508 mutation, interventions that overcome the CFTR protein-processing problems caused by this mutation might have important implications for new ways of treating CF.

“In the field of CF therapeutics there’s great interest in identifying ways to restore the function of this misprocessed protein,” McCray says. “We were very surprised that manipulating this microRNA regulated gene network had this rescuing effect. This opens up a new avenue for the development of CF therapies.”

To view the original article, please visit: http://www.sciencedaily.com/releases/2012/08/120801093844.htm

Source: Cystic Fibrosis Foundation

A Phase 2 clinical trial of Kalydeco™ in combination with VX-809 showed significant improvements in lung function in people with the most common CF mutation, according to final results announced today by Vertex Pharmaceuticals Inc.

Both Kalydeco and VX-809, a CF drug in development, are designed to treat the root cause of cystic fibrosis. Vertex developed Kalydeco and VX-809 with significant financial, clinical and scientific support from the Cystic Fibrosis Foundation.

The 56-day study enrolled 109 people, ages 18 and older, with one or two copies of Delta F508. People in the study with two copies of Delta F508 (the most common CF mutation) who received the highest dose of VX-809 combined with Kalydeco showed the greatest improvement in lung function. Vertex released preliminary results from the Phase 2 trial earlier this year.

Based on these final results, Vertex plans to begin a pivotal trial of the combination treatment in people with two copies of Delta F508 in early 2013. Pivotal trials typically aim to gather data that the U.S. Food and Drug Administration (FDA) could use to decide whether to approve a potential drug.

“The improvements seen in lung function are very encouraging, and we are pleased that Vertex plans to move forward quickly with a pivotal trial,” said Robert J. Beall, Ph.D., president and CEO of the CF Foundation. “We still have significant work ahead of us, but the entire CF community can take pride in its role in making this important step possible. We thank the trial volunteers and their families, clinicians and scientists, and our dedicated volunteers and donors across the country.” 

Participants with one copy of the Delta F508 mutation also showed improvements in lung function, compared with those who received a placebo — though smaller than the improvements seen in those with two copies of Delta F508. Vertex said it plans to conduct additional studies of Kalydeco and VX-809 in those with one copy of Delta F508.

About 50 percent of people with CF in the United States have two copies of the Delta F508 mutation; an additional 40 percent of people in the United States have one copy.

The FDA approved Kalydeco in January 2012 for people with the G551D mutation of CF ages 6 and older. About 4 percent of people in the United States have the G551D mutation.

People with CF and their families who have questions about the Phase 2 results can contact Vertex Medical Information at 1-877-634-8789.

For more information, read Vertex’s press release: http://investors.vrtx.com/releasedetail.cfm?ReleaseID=687394