Category: Therapies

ORKAMBI is a prescription medicine used for the treatment of cystic fibrosis (CF) in patients age 12 years and older who have two copies of the F508del mutation (F508del/F508del) in their CFTR gene.

ORKAMBI should not be used in patients other than those who have two copies of the F508del mutation in their CFTR gene.

It is not known if ORKAMBI is safe and effective in children under 12 years of age.

Please visit http://www.orkambi.com/ to learn more about its approval, who should take it, and how to start your conversation with your healthcare provider. 

SOURCE — Please read the original press release here — SOURCE

FDA decision expected by July 5, 2015 PDUFA date

Approximately 8,500 people with cystic fibrosis in the U.S. have two copies of the F508del mutation and are ages 12 and
older

BOSTON–(BUSINESS WIRE)– Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that the U.S. Food and Drug Administration’s (FDA) Pulmonary-Allergy Drugs Advisory Committee (PADAC) voted 12 to 1 to recommend that the FDA approve ORKAMBITM (lumacaftor/ivacaftor) for use in people with cystic fibrosis (CF) ages 12 and older who have two copies of the F508del mutation in the CFTR gene. Advisory committees provide the FDA with independent scientific and medical advice on safety, effectiveness and appropriate use of potential new medicines. The FDA is expected to make a decision on the approval of ORKAMBI by July 5, 2015 under the Prescription Drug User Fee Act (PDUFA). The FDA is not bound by the committee’s recommendation but often follows its advice. If approved, ORKAMBI will be the first and only medicine to treat the underlying cause of CF for eligible people with CF ages 12 and older with two copies of the F508del mutation in the CFTR gene. People with two copies of the F508del mutation represent the largest group of people with CF. There are approximately 8,500 people ages 12 and older with two copies of the F508del mutation in the U.S.

“Today’s positive recommendation brings the cystic fibrosis community one step closer to potential approval of the first medicine to treat the underlying cause of this disease for many more people,” said Jeffrey Chodakewitz, M.D., Executive Vice President and Chief Medical Officer at Vertex. “We look forward to continuing to work with the FDA and other regulatory agencies throughout the world to make ORKAMBI available to eligible patients as soon as possible.”

Cystic fibrosis is a rare genetic disease that is caused by defective or missing CFTR proteins resulting from mutations in the CFTR gene. The defective or missing proteins result 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.

ORKAMBI is a combination of lumacaftor, which is designed to increase the amount of functional protein at the cell surface by addressing the processing and trafficking defect of the protein, and ivacaftor, which is designed to enhance the function of the CFTR protein once it reaches the cell surface. ORKAMBI is an oral medicine that, if approved, would be taken as fully coformulated tablets that contain both lumacaftor and ivacaftor.

SOURCE

Yale researchers successfully corrected the most common mutation in the gene that causes cystic fibrosis, a lethal genetic disorder.

The study was published April 27 in Nature Communications.

Cystic fibrosis is an inherited, life-threatening disorder that damages the lungs and digestive system. It is most commonly caused by a mutation in the cystic fibrosis gene known as F508del. The disorder has no cure, and treatment typically consists of symptom management. Previous attempts to treat the disease through gene therapy have been unsuccessful.

To correct the mutation, a multidisciplinary team of Yale researchers developed a novel approach. Led by Dr. Peter Glazer, chair of therapeutic radiology, Mark Saltzman, chair of biomedical engineering, and Dr. Marie Egan, professor of pediatrics and of cellular and molecular physiology, the collaborative team used synthetic molecules similar to DNA — called peptide nucleic acids, or PNAs — as well as donor DNA, to edit the genetic defect.

“What the PNA does is clamp to the DNA close to the mutation, triggering DNA repair and recombination pathways in cells,” Egan explained.

The researchers also developed a method of delivering the PNA/DNA via microscopic nanoparticles. These tiny particles, which are billionths of a meter in diameter, are specifically designed to penetrate targeted cells.

In both human airway cells and mouse nasal cells, the researchers observed corrections in the targeted genes. “The percentage of cells in humans and in mice that we were able to edit was higher than has been previously reported in gene editing technology,” said Egan. They also observed that the therapy had minimal off target, or unintended, effects on treated cells.

While the study findings are significant, much more research is needed to refine the genetic engineering strategy, said Egan. “This is step one in a long process. The technology could be used as a way to fix the basic genetic defect in cystic fibrosis.”

Other Yale authors include Nicole Ali McNeer, Kavitha Anandalingam, Rachel J. Fields, Christina Caputo, Sascha Kopic, Anisha Gupta, Elias Quijano, Lee Polikoff, Yong Kong, Raman Bahal, and John P. Geibel.

This research was supported in part by the NIGMS Medical Scientist Training Program T32GM07205 (to N.A.M.), the Hartwell Foundation (to M.E.E.) and the National Institute of Health grants R01HL082655 and R01AI112443 (to P.M.G) and R01EB000487 (to W.M.S.).

SOURCE: LA TIMES

Using soil from a grassy field in Maine and a miniaturized diffusion chamber, scientists have cultivated a microbe that could help tame the spread of antibiotic-resistant superbugs.

When tricked into growing in a lab, the microbe makes a compound that kills strains of tuberculosis, MRSA and other deadly pathogens that are immune to even the most powerful drugs. Tests in mice showed that the newfound molecule is “exquisitely active against some very hard-to-deal-with bugs,” said Northeastern University microbiologist Kim Lewis, the senior author of a study published Wednesday in the journal Nature.

A previously uncultured bacterium, Eleftheria terrae, is able to make teixobactin, a new antibiotic for which there is no detectable resistance. (William Fowle, Northeastern University)
Experts said the discovery could lead to a new class of antibiotics for the first time in decades. If so, it would give doctors a much-needed weapon in the microbial arms race that has tilted in favor of bacteria.

The World Health Organization has warned that the rise of antibiotic-resistant bacteria threatens to undermine the advances made by modern medicine. In the United States, more than 2 million people are sickened by such infections each year, and 23,000 of them die as a result.

Most of the workhorse drugs in use today were developed at least 50 years ago. During the heyday of antibiotic research immediately after World War II, soil microbes yielded the mainstays in the fight against deadly infections.

Lewis and his colleagues revived that idea to find a new species of bacteria they named Eleftheria terrae.

Soil is chock full of microbes, but most don’t readily form colonies in petri dishes. In addition, many of the organisms uncovered in such samples are identical or similar to ones already developed.

“You inevitably are rediscovering penicillin and streptomycin,” Lewis said.

To encourage new bacteria to grow, the researchers couldn’t just dump their dirt into a laboratory dish. Instead, they isolated minuscule samples in diffusion chambers that functioned as bacterial incubators. Then they put the samples back in the soil.

“Essentially we’re tricking the bacteria,” Lewis said. “They start growing and form colonies.”

The experiment yielded about 10,000 strains of bacteria, which were laboriously sorted and studied.

Researchers then checked to see whether any of the strains could kill streptococcus bacteria. Finally, they extracted the antibacterial molecule from E. terrae, one of the more promising strep killers.

Trials on mice showed that the molecule, which they called teixobactin, rapidly cleared infections of drug-resistant strains of Mycobacterium tuberculosis and Staphylococcus aureus bacteria, according to the study. They also felled two kinds of bacteria that cause serious infections of heart tissue, Lewis said.

The compound attacks these and other gram-positive bacteria by binding to chemicals essential to forming cell walls, causing them to break down.

Brilacidin is the first in the new class of antibiotics being developed by Cellceutix with a wide potential application. The media has yet to catch on. A much bigger story than teixobactin as it is now has proven safety and efficacy in humans. Brilacidin and its analogs are the first new…

“Not only one target is attacked, but multiple targets, and they are all lethal,” said study coauthor Tanja Schneider of the University of Bonn in Germany.

This mechanism of destruction makes it much more difficult for bacteria to develop resistance to teixobactin. Most antibiotics attack proteins, but the DNA that codes for these proteins is known to mutate. Over time, some of these mutations allow bacteria to evade a drug’s lethal effects.

The DNA that includes instructions for making cell walls is far less likely to mutate, researchers said. Indeed, when they tried to encourage bacteria to develop resistance to teixobactin, they couldn’t.

Lewis said teixobactin kills so quickly that target bacteria will have less time in which to develop resistance.

It took about 30 years for bacteria to develop resistance to a similarly acting antibiotic, the study noted. Researchers said any new drug probably would remain effective at least as long.

Converting teixobactin into a safe, effective and marketable drug could take about five years and cost several hundred million dollars, according to the academic-biotech coalition that made the discovery.

“We will probably be in clinical trials two years from now,” Lewis said.

Lewis said the successful cultivation of the proteobacteria that produced the antibiotic suggests that mining soil for new medicines may once again prove fruitful in the search for weapons against human pathogens.

Researchers said they would work to broaden the spectrum of bacteria the molecule can fight, and tinker with its chemistry to ensure it can be administered in reasonable doses.

Although the study represents a “new twist” in the effort to develop new antibiotics, it remains untested in humans, said Dr. Richard Seabrook, head of business development at the London-based Wellcome Trust, which was not involved in the study. “We will not know whether teixobactin will be effective in humans until this research is taken from animal testing in the lab to clinical trials,” he said.

NovoBiotic Pharmaceuticals of Cambridge, Mass., owns the patent for the new molecule. Several of the researchers have financial stakes in the company.

Financial support for the research also came from the U.S. National Institutes of Health and the German government.

geoffrey.mohan@latimes.com

Twitter: @LATsciguy

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
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or
Europe: Megan Goulart, +41 22 593 6066

Source: Vertex Pharmaceuticals Incorporated

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SOURCE – VERTEX OFFICIAL PRESS RELEASE

SOURCE: VERTEX PRESS RELEASE

FDA Advisory Committee Recommends Approval of KALYDECO® (ivacaftor) for Use in People with Cystic Fibrosis Ages 6 and Older Who Have the R117H Mutation

BOSTON–(BUSINESS WIRE)– Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that the U.S. Food and Drug Administration’s Pulmonary Allergy Drugs Advisory Committee (PADAC) voted 13-2 to recommend approval of KALYDECO® (ivacaftor) in people with cystic fibrosis (CF) ages 6 and older who have the R117H mutation in the cystic fibrosis transmembrane regulatory (CFTR) gene, which is the indication being reviewed by the FDA.

“Today’s recommendation is a positive and important step toward making ivacaftor available for people ages 6 and older with the R117H mutation,” said Jeffrey Chodakewitz, M.D., Senior Vice President and Chief Medical Officer at Vertex.

Advisory committees provide the FDA with independent scientific and medical advice on safety, effectiveness and appropriate use of potential new medicines. The FDA is not bound by the committee’s recommendation, but often follows its advice. The FDA is expected to make a decision on the approval of ivacaftor by December 30, 2014 under the Prescription Drug User Fee Act (PDUFA).

Cystic fibrosis is caused by a defective or missing CFTR protein resulting from mutations in the CFTR gene. KALYDECO is currently approved to treat more than 2,600 people ages 6 and older in North America, Europe and Australia who have specific mutations in the CFTR gene. In the United States, these mutations include G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P and G1349D. In people with the R117H mutation, the CFTR protein reaches the cell surface but does not function properly. Approximately 500 people ages 6 and older have this mutation in the United States.

Please download the full press release here.