Category: Therapies

Source: American Thoracic Society press release

Adding inhaled dry powder mannitol to standard therapy for cystic fibrosis produced sustained improvement in lung function for up to 52 weeks, according to a new study. Along with the treatment’s efficacy and good safety profile, the convenience and ease of administration of mannitol treatment may improve adherence with therapy in these patients.

In the double-blind study, which was supported by Pharmaxis Limited, 318 patients were randomized to treatment with 400 mg bid inhaled mannitol or 50 mg bid inhaled mannitol (control group) for 26 weeks, followed by an additional 26 weeks of open-label active treatment. A 50 mg dose was chosen as the control because it was felt it would not be clinically effective, based on an earlier dose escalation study. Mannitol was given on top of a background of typical concomitant therapy such as recombinant human deoxyribonuclease and inhaled antibiotics.

The findings were published online ahead of print publication in the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine.

“Patients in the treatment group showed a 106.5 mL mean improvement in forced expiratory volume in one second (FEV1), an 8.22 percent improvement from baseline, compared with a 52.4 mL improvement (4.47 percent) in the control group,” said lead author Moira L. Aitken, MD, professor of pulmonary and critical care medicine at the University of Washington Medical Center. “Forced vital capacity increased 136.3 mL in the treatment group, compared with 65.0 mL in the control group. Treated patients also experienced fewer pulmonary exacerbations than controls.”

The difference in absolute FEV1 between the study and control groups approached statistical significance (p=0.059), while the difference in relative change from baseline FEV1 between groups reached significance (p=0.029). Improvements in FEV1 were maintained in the treatment group during the 26-week open-label extension phase of the study. In the control group, mean FEV1 improved 84.0 mL (6.3 percent) from baseline during the open-label phase.

Patients in the treatment and control groups experienced similar rates of adverse events. Given a possible influence of mannitol on lung microbiology, qualitative sputum microbiology was performed for Staphylococcus aureus and Pseudomonas aeruginosa during the double-blind study period. No qualitative changes in microbiology results from baseline were observed in either group.

Compliance was good in both groups, with 85.2 percent of patients in the treatment group and 88.7 percent of controls using 60 percent or more of the drug dispensed.

Although the primary end point for the study, the difference in absolute FEV1 between the treatment and control groups, did not reach significance, this may have been due to use of a single baseline visit to establish baseline FEV1 values. When baseline FEV1 values were calculated as an average of FEV1 values over two baseline visits, as in prior clinical intervention studies, the overall increase in absolute FEV1 was significantly (p=0.0008) greater in the treatment group. The 50 mg dose of mannitol used in the control group may also have had some benefit, which limited the absolute difference between groups.

“In our patients with cystic fibrosis, treatment with inhaled mannitol resulted in sustained improvements in lung function over 12 months, with a favorable safety profile,” concluded Dr. Aitken. “In addition, the dry-powder inhaler used to administer mannitol is small, portable, easy to use and doesn’t require thorough cleaning and disinfection after each use, which may help patients better adhere to treatment. Our results support the use of inhaled mannitol for the daily management of cystic fibrosis.”

Source: Vertex Pharmaceuticals press release

Vertex Pharmaceuticals Incorporated announced today that the U.S. Food and Drug Administration (FDA) has accepted the New Drug Application (NDA) for KALYDECO™ (ivacaftor) and granted the company’s request for six-month priority review.

KALYDECO targets the defective protein that causes cystic fibrosis (CF) in a subset of people with the disease. If approved, KALYDECO will be the first treatment to target the underlying cause of CF.

The FDA grants priority review to medicines that offer major advances in treatment or provide a treatment where no adequate therapy exists. A target review date of April 18, 2012, is set under the Prescription Drug User Fee Act (PDUFA) for the FDA’s approval decision, which is four months earlier than the standard review time of 10 months.

In addition, Vertex announced today that its marketing authorization application (MAA) for KALYDECO has been validated by the European Medicines Agency (EMA). Validation indicates that the application is complete and starts the regulatory review process by the Committee for Medicinal Products for Human Use (CHMP). Earlier this year, the EMA accepted Vertex’s request for accelerated assessment, which is granted to new medicines of major public health interest and shortens the EMA’s review time.

“If approved, KALYDECO will be the first treatment to target the underlying cause of CF,” said Peter Mueller, Ph.D., Chief Scientific Officer and Executive Vice President of Global Research and Development at Vertex. “The commitments by the FDA and the EMA to expedite their reviews of our applications underscore the significant potential of KALYDECO to help people living with cystic fibrosis.”

CF is caused by defective or missing cystic fibrosis transmembrane conductance regulator (CFTR) proteins resulting from mutations in the CFTR gene. The absence of functional CFTR proteins results in poor flow of salt and water across cell membranes 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.

In people with CF who have a gating defect, CFTR proteins are present at the cell surface but do not function properly. The most common gating defect is caused by the G551D mutation. Approximately 4 percent of those with CF, or about 1,200 people in the United States and 1,000 people in Europe, are believed to have this mutation. KALYDECO is designed to keep the CFTR channels at the cell surface open longer to improve the transport of chloride ions across the cell membrane in people who have gating mutations. The U.S. application seeks approval for KALYDECO in people with the G551D mutation. The application submitted in Europe includes a request for all gating mutations.

The regulatory submissions are supported by results from two Phase 3 studies, STRIVE and ENVISION, in which people with CF who had at least one copy of the G551D mutation and were treated with KALYDECO experienced rapid, significant and sustained improvements across a variety of disease measures, including lung function. The majority of adverse events associated with KALYDECO were mild to moderate in severity and non-serious. Fewer people in the KALYDECO treatment groups than in the placebo groups discontinued treatment due to adverse events. These data showed that treating the underlying cause of CF may improve outcomes for people with the disease.

About KALYDECO

KALYDECO (ivacaftor, VX-770) is Vertex’s lead medicine in development for the treatment of people with cystic fibrosis. Known as a CFTR potentiator, this oral medicine in development aims to help CFTR protein function more normally once it reaches the cell surface, which is believed to help hydrate and clear mucus from the airways. Vertex retains worldwide rights to develop and commercialize KALYDECO (kuh-LYE-deh-koh). The brand name KALYDECO has been approved by the EMA and provisionally approved by the FDA, but KALYDECO has not been granted marketing authorization or approval from any regulatory authority.

Source: Diabetic Live

In addition to Type 1 and Type 2 diabetes, there is another variant of the disease: cystic fibrosis-related diabetes. It differs in some important ways from Type 1 and Type 2 diabetes and it requires different treatment methods.

Patients with cystic fibrosis experience decreased nutritional and pulmonary health several years before they’re diagnosed with cystic fibrosis-related diabetes (CFRD). According to Amanda Leonard, a senior pediatric clinical dietician at the Johns Hopkins Cystic Fibrosis Center, early diagnosis and treatment can significantly improve life expectancy in patients who develop CFRD.

“Screening early and knowing which patients are at risk is really important,” said Leonard at a pediatric nutrition meeting sponsored by Johns Hopkins University.

CFRD does “share some components” with Type 1 and Type 2 diabetes, says Leonard, but it’s also different in some important ways. Patients with CFRD typically experience decline in lung function, protein catabolism, weight loss, and an increased rate of mortality. Ketones rarely appear in patients with CFRD, and the development of the disease does not appear to be related to autoimmune function.

In cystic fibrosis patients at the age of 40, the rate of CFRD is over 50 percent. According to Leonard, more patients develop CFRD in the 20-24 year old range than any other age; meanwhile, Type 1 diabetes usually develops in childhood and Type 2 diabetes usually develops in mid-to-late adulthood.

“In CFRD there is a severe insulin deficiency, but it’s not as complete as in type 1,” said Leonard. Physicians define CFRD as the presence of at least two of the following criteria on at least two occasions: hemoglobin A1c of at least 6.5 percent; fasting glucose level of at least 126 mg/dL; and a two-hour oral glucose tolerance test of plasma glucose at least 200 mg/dL.

Leonard says that CFRD isn’t quite as easy to identify as other types of diabetes. In patients with CFRD, a two-hour oral glucose tolerance test (OGTT) can range from 140 to 199 mg/dL while fasting glucose can range from 100 to 125 mg/dL. According to Leonard, it’s “not quite diabetes, but it’s not quite right either.” The disease is “not an all or nothing kind of thing. It’s not that either you have it or you don’t. It can be transient in nature, and there’s a spectrum,” she continued.

Outpatient OGTTs are the best option for routine CFRD testing in clinically stable patients. Cystic fibrosis patients are recommended to begin OGTT screening for diabetes when they reach 10 years of age.

While HbA1c alone cannot be used as to screen for CFRD due to a high rate of false positives, a low HbA1c can confirm a diagnosis from other symptoms.

Patients who are hospitalized due to pulmonary exacerbation and/or treatment with corticosteroids should be tested with both fasting and two-hour post-meal blood glucose monitoring. The patient is diagnosed with CFRD when fasting or post-meal hyperglycemia lasts longer than 48 hours.

Patients with CFRD are treated with insulin; other treatment methods have not shown benefits for patients and are not recommended over insulin. “Insulin is the treatment of choice. Oral agents do not seem to work as well,” said Leonard.
CFRD patients have the same blood glucose goals as other diabetes patients, with an HbA1c goal of less than 7.0 percent. However, goals are adjusted for each individual patient.

Nutritional recommendations for patients with CFRD are based on those for patients with cystic fibrosis. CFRD patients may also benefit from counting carbohydrates to ensure safe blood glucose levels.

Vertex Pharmaceuticals Inc. today announced the submission of a new drug application to the U.S. Food and Drug Administration for KALYDECO™ (VX-770, ivacaftor), a medicine in development that targets the defective protein that causes cystic fibrosis.

KALYDECO (kuh-LYE-deh-koh) was studied among people with CF ages six and older who have at least one copy of the G551D mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. In the United States, approximately 4 percent of people with CF are estimated to have at least one copy of the G551D mutation in the CFTR gene.

Global Phase 3 pivotal studies of KALYDECO showed significant and sustained improvements in lung function and other measures of disease in people with CF who had at least one copy of the G551D mutation. The majority of adverse events associated with KALYDECO were mild to moderate in severity and non-serious. Fewer people in the KALYDECO treatment groups than in the placebo groups discontinued treatment due to adverse events. If approved, KALYDECO will be the first treatment to target the underlying cause of CF.

The U.S. submission includes a request for priority review, which, if granted, would shorten the FDA’s anticipated review time from 10 to six months. The FDA grants priority review status for several reasons, including if the medicine is considered a major advance in treatment. Vertex also plans to submit a marketing authorization application (MAA) for KALYDECO with the European Medicines Agency (EMA) by the end of October 2011. The EMA has accepted Vertex’s request for accelerated assessment, which is granted to new medicines of major public health interest and shortens the review time from 210 days to 150 days following the start of the review. Additionally, Vertex submitted requests to the FDA and EMA to use the trade name KALYDECO (ivacaftor) for VX-770.

“KALYDECO represents a completely new approach to the treatment of CF by targeting the underlying cause of the disease,” said Matthew Emmens, Chairman, President and Chief Executive Officer of Vertex. “This is our second new drug application in less than a year, which is a significant achievement and underscores our commitment to developing new medicines for people with serious diseases.”

“The CF Foundation is thrilled that our collaboration with Vertex has contributed to an important potential new medicine for the treatment of some people with CF,” said Robert J. Beall, Ph.D., President and CEO of the CF Foundation. “The results of the KALYDECO studies have opened the door to a new way of treating CF and we hope that this approach will lead to the development of other targeted medicines for all people with this disease.”

CF is a life-threatening genetic disease that is caused by mutations in the CFTR gene that result in defective or missing CFTR proteins. The absence of functional CFTR proteins results in poor flow of salt and water across cell membranes 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. Currently available medicines have helped improve treatment and care for people living with CF by treating the symptoms and some of the complications of the disease.

Various mutations in the CFTR gene lead to CF. In some people, CFTR proteins are present at the cell surface but do not function properly. This dysfunction is known as a gating defect, the most common of which is the G551D mutation. Approximately 4 percent of those with CF, or about 1,200 people in the United States, are believed to have the G551D mutation. KALYDECO is designed to keep the CFTR channels at the cell surface open longer to improve the transport of chloride ions across the cell membrane in people who have gating mutations. KALYDECO has been studied in people with CF ages six and older who carry at least one copy of the G551D mutation.

“These regulatory applications are a reflection Vertex’s 13-year research and development effort and the commitment of hundreds of doctors, nurses, patients and their caregivers who participated in the studies of KALYDECO,” said Peter Mueller, Ph.D., Chief Scientific Officer and Executive Vice President of Global Research and Development at Vertex. “We look forward to working with U.S. and European regulatory agencies to make KALYDECO available as quickly as possible.”

Highlights of the KALYDECO Phase 3 Registration Program

These regulatory submissions are supported by results from two Phase 3 studies, STRIVE and ENVISION, in which people with CF who had at least one copy of the G551D mutation and were treated with KALYDECO experienced rapid, significant and sustained improvements across a variety of disease measures, including lung function. These data support the hypothesis that treating the underlying cause of CF may improve outcomes for people with the disease. A Phase 2 study, DISCOVER, was conducted in people who had two copies of the F508del mutation, the most common CFTR mutation, and provided additional safety information to support the regulatory applications for KALYDECO.

Overview of KALYDECO Discovery and Development Effort

KALYDECO was discovered as part of a collaboration with Cystic Fibrosis Foundation Therapeutics, Inc. (CFFT), the nonprofit drug discovery and development affiliate of the CF Foundation, to discover and develop novel CFTR modulators.

Expanded Access Programs for KALYDECO

In recognition of the immediate needs of some people with CF, an expanded access program for KALYDECO is currently open at participating clinical trial sites in the United States. This program is designed to provide KALYDECO to people ages six and older who have at least one copy of the G551D mutation, are in critical medical need and may benefit from treatment prior to potential FDA approval in the United States.

Vertex is working toward implementing additional expanded access programs in other countries, with a goal of opening programs for eligible patients by the end of 2011.

For more information, please call Vertex Medical Information at 1-877-634-VRTX (8789).

Source: Cystic Fibrosis Foundation

The New England Journal of Medicine, the world’s most widely read and influential medical periodical, features a study this week about a Phase 3 clinical trial of Kalydeco™ (VX-770), a potential CF therapy undergoing review for approval by the U.S. Food and Drug Administration (FDA).

If approved, Kalydeco will be the first drug on the market that targets the underlying cause of cystic fibrosis — a faulty gene and its protein product, CFTR — rather than just the symptoms of the disease.

The maker of Kalydeco, Vertex Pharmaceuticals, Inc., is seeking approval for the drug in people ages 6 and older with at least one copy of the G551D mutation of CF.

Kalydeco was developed by Vertex with CF Foundation support and research input.

The VX-770 study is “a great victory in the war against genetic diseases and marks the end of the beginning for the treatment of the cystic fibrosis defect,” writes Pamela B. Davis, M.D., Ph.D., dean of the Case Western Reserve University School of Medicine, in an independent editorial accompanying the Journal study.

The article presents results from a Phase 3 clinical trial of Kalydeco in people ages 12 and older with the G551D mutation of CF. People who took the drug showed dramatic improvements in lung function and other key symptoms of CF, compared with those who did not receive Kalydeco, and they maintained these improvements throughout the nearly yearlong trial.

“The New England Journal of Medicine study marks an important and exciting milestone for the cystic fibrosis community, and it confirms that we are one step closer to finding a cure for the disease,” said Robert J. Beall, Ph.D., president and CEO of the CF Foundation. “With Kalydeco on track for possible FDA approval in 2012, we are moving forward energetically to identify and develop additional therapies that target the underlying cause of the disease to treat all people with CF.”

Kalydeco is currently being evaluated in combination with another oral drug in development, VX-809, in people with at least one copy of the most common mutation of CF, Delta F508. Vertex is enrolling participants for the second part of an ongoing Phase 2 study of the two drugs.

In 2012, Vertex also plans to begin a Phase 2 clinical trial of Kalydeco in combination with another potential therapy, VX-661, in people with two copies of the Delta F508 mutation of CF.

Insmed Inc., a biopharmaceutical company, today announced that it has been notified by the U.S. Food and Drug Administration that it is continuing the clinical hold previously placed on Insmed’s phase 3 clinical trials for ARIKACE® (liposomal amikacin for inhalation) in cystic fibrosis patients with Pseudomonas lung infections.

Insmed has not yet received a response from FDA regarding the clinical hold previously placed on Insmed’s phase 3 clinical trials for ARIKACE in patients with non-tuberculous mycobacterial (NTM) lung disease. 

As announced on August 1, the clinical holds placed on ARIKACE in CF and NTM were based on an initial review by FDA of the interim results of a long-term rat inhalation carcinogenicity study reported to the agency by Insmed with ARIKACE.  At that time, FDA requested additional information on ARIKACE and data from the rat study.  Insmed submitted its complete response to this request before the end of August.

Insmed has been informed by FDA that, based on its review of the information provided to date, including the rat inhalation carcinogenicity study results, the agency has insufficient information to assess the risks for ARIKACE in CF patients.  FDA has requested additional information from Insmed, including that Insmed conduct a dog inhalational nine-month toxicity study of ARIKACE to determine if the findings of the rat inhalation carcinogenicity study are also demonstrated in a non-rodent model, and to propose a CF patient population/disease state where the risk-benefit profile of ARIKACE may be more favorable.

“Insmed is in the process of assessing the impact that FDA’s recent requests and the continuation of the clinical hold will have on our phase 3 clinical trials for ARIKACE in CF,” said Timothy Whitten, President and CEO of Insmed.  “Once we have a better understanding of the FDA’s requests and their implications, we will provide a further update to the market.”

Source: Insmed press release

Pulmatrix, a clinical stage biotechnology company discovering and developing a new class of therapies for the prevention, treatment and control of respiratory diseases, today announced that its clinical development plans will focus on the company’s lead clinical candidate in chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF).

The company has initiated two Phase 1b studies with PUR118, a novel inhaled dry powder therapeutic, in patients with COPD which includes patients with emphysema and chronic bronchitis. Pulmatrix’s plans to advance its clinical development programs coincide with additional support from a $14 million private financing, also announced today.

The decision to initiate these Phase 1b studies is based upon successful completion, in June 2011, of the clinical portion of two Phase 1 studies with PUR118 in healthy volunteers. In addition, another clinical trial in asthmatic patients using PUR003, a liquid product candidate with the same active drug as PUR118, successfully completed the clinical phase in May 2011. The Phase 1 results to date, including data from studies with PUR118 in healthy volunteers and PUR003 in both healthy volunteers and patients with asthma, all demonstrated favorable safety and tolerability.

“Our clinical program explores and defines the broad capabilities of our iCALM products for a wide range of serious progressive respiratory diseases, including COPD, asthma, cystic fibrosis, and other inflammatory airways conditions. With iCALM, we have the potential to have a single, simple, and convenient drug that could be used by tens of millions of patients affected by chronic respiratory diseases,” said Robert Connelly, CEO of Pulmatrix. “We have the resources, team, and proprietary technology to deliver inhaled drugs that can transform the treatment landscape for chronic and infectious inflammatory airways diseases.”

The randomized, ascending multiple-dose Phase 1b studies will primarily assess the safety and tolerability of PUR118 administered via a dry powder inhaler to patients with mild to moderate COPD. These studies will also explore the impact of PUR118 on airway inflammation and clearance of respiratory secretions, key factors in preventing and reducing the severity of exacerbations in patients with inflammatory airway conditions, including COPD and Cystic Fibrosis (CF).

“Our clinical data to date suggest that our novel iCALM therapies, including our most advanced formulation PUR118, will be well tolerated in the targeted patient populations with inflammatory airways conditions,” said John Hanrahan, MD, MPH, Chief Medical Officer & Senior Vice President of Pulmatrix. “iCALM is uniquely suited to address respiratory exacerbations: the most serious threats to patients with inflammatory airways conditions. iCALM delivers this important therapeutic benefit to patients by the combined effects of reducing airway inflammation, augmenting airway clearance, and priming the airway’s innate defenses to combat respiratory pathogens. iCALM holds promise to impact all three mechanisms by a mode of action different from existing and alternative emerging therapies.”

Source: Pulmatrix press release

Vertex Pharmaceuticals Inc. today announced it plans to submit to the U.S. Food and Drug Administration in October a new drug application for VX-770, a promising CF therapy.  Following is information on the announcement from Vertex and the Cystic Fibrosis Foundation.

---

FROM THE CYSTIC FIBROSIS FOUNDATION WEBSITE:

Vertex Pharmaceuticals Inc. announced today it plans to submit a New Drug Application for VX-770, a potential CF medicine, to the U.S. Food and Drug Administration (FDA) in October. The company is seeking approval for the drug in people age 6 and older with at least one copy of the G551D mutation of cystic fibrosis.

About 4 percent of people with CF in the U.S. have the G551D mutation.

Vertex also said it expects to begin testing the drug in additional CF patient groups in the first half of 2012. This includes a study of the drug in children age 2 to 5 with the G551D mutation and studies of VX-770 in people with CF with other “gating” mutations besides G551D.

“We are thrilled that Vertex is preparing to apply for FDA approval this October, keeping VX-770 on track for possible approval next year,” said Robert J. Beall, Ph.D., president and CEO of the Cystic Fibrosis Foundation. “We’re also extremely encouraged the company plans to broaden its VX-770 program to evaluate whether greater numbers of people with CF can potentially benefit from this treatment.”

Additional VX-770 Studies in People with Gating and Other CF Mutations

In gating mutations such as G551D, the defective protein in CF moves to its proper place on the cell surface but does not function correctly. It acts instead like a locked gate, impeding the proper flow of salt and fluid in and out of the cell. VX-770 aims to unlock the gate, helping to restore the function of the defective protein.

The new studies may also include people with CF mutations other than gating mutations, Vertex said.

Vertex will provide additional information on these studies after it has completed discussions with regulatory agencies.

More Studies of Combination Therapies to Treat Most Common CF Mutation

In September, Vertex plans to begin the second part of a Phase 2 clinical trial evaluating VX-770 in combination with another experimental drug, VX-809.

The study will enroll people with at least one copy of the Delta F508 mutation, the most common CF mutation, and is expected to evaluate higher dosing levels over a longer period of time than in the first part of the combination trial, completed earlier this year.

Vertex also plans to start a clinical trial by the end of 2011 that will study VX-770 in combination with a third drug in development, VX-661, in people with two copies of the Delta F508 mutation.

The CF Foundation worked with Vertex to discover VX-770, VX-809 and VX-661 and has provided substantial scientific, financial and clinical support throughout the development process.

Earlier this year, the Foundation announced an expanded collaboration with Vertex, which includes an investment of up to $75 million over five years to accelerate the development of new drugs to treat the underlying cause of CF, including VX-661.

---

EXCERPT FROM THE VERTEX PHARMACEUTICALS PRESS RELEASE:

Submission of VX-770 NDA and MAA on Track for October 2011

The Phase 3 program for VX-770, Vertex’s cystic fibrosis transmembrane conductance regulator protein (CFTR) potentiator, is now complete. In October, Vertex plans to submit both its VX-770 NDA to the U.S. Food and Drug Administration (FDA) and its VX-770 MAA to the European Medicines Agency (EMA). Additional regulatory submissions are planned for Canada and other countries following the submissions of the NDA and MAA. Vertex is seeking approval of VX-770 in people six years of age and older who have at least one copy of the G551D mutation in the CFTR gene.

Additional Studies of VX-770 Planned for 2012

Pediatric Study: The Phase 3 program for VX-770 was focused on people ages 6 and older with the G551D mutation. In the first half of 2012, Vertex plans to begin the first study of VX-770 in children younger than 6 years of age. The study is expected to enroll children ages 2 through 5 and will evaluate the safety, tolerability, and effect on sweat chloride and other measures of clinical efficacy using a pediatric formulation of VX-770.

Studies of VX-770 in People with other CFTR Mutations: The G551D mutation is the most common gating mutation, present in approximately 4 percent of all people with CF. In the first half of 2012, Vertex plans to begin two clinical studies of VX-770 in people with CF who have other CFTR mutations where, based on in vitro data, VX-770 may help improve the function of CFTR proteins at the cell surface. These additional studies are expected to enroll people with CF who have certain other gating mutations that result in the CFTR protein functioning abnormally at the cell surface, as well as people with other mutations that result in some residual CFTR function. A goal of the trials will be to generate data to support the evaluation of the use of sweat chloride measurements as a marker for clinical benefit in people with CF.

Additional information on these studies will be provided upon completion of discussions with regulatory agencies in the U.S. and E.U.

Phase 2 Trials Combining Two CFTR Modulators for the Treatment of People with the Most Common Mutation of CF

Vertex is conducting an exploratory Phase 2 clinical trial to evaluate combination regimens of VX-770 and VX-809, a CFTR corrector, in people with the most common mutation in CF, known as F508del. Vertex recently completed the first part of the trial and is on track to initiate the second part of the trial in September 2011. Part Two of this trial will include dosing of VX-809 alone for at least four weeks followed by dosing of VX-770 and VX-809 in combination for at least four weeks. Similar to Part One, the primary goals of the second part of the trial will be to evaluate the safety and tolerability and the effect of the combination of VX-770 and VX-809 on CFTR function as measured by sweat chloride. Lung function will be measured as a secondary endpoint. The trial is expected to evaluate higher doses of VX-809 than the 200 mg dose studied in the first part of the trial and to enroll people with CF who have one copy or two copies of the F508del mutation.

Vertex also plans to initiate a Phase 2a clinical trial to evaluate combination regimens of VX-770 and VX-661, another CFTR corrector, by the end of 2011. This trial will evaluate people with two copies of the F508del mutation.

Source: Vertex Pharmaceuticals and Cystic Fibrosis Foundation

Insmed Inc., a biopharmaceutical company, announced that the U.S. Food and Drug Administration (FDA) has notified the company that the agency has placed a clinical hold on Insmed’s phase 3 clinical trials for ARIKACE® (liposomal amikacin for inhalation) in cystic fibrosis (CF) patients with Pseudomonas lung infections and patients with non-tuberculous mycobacterial (NTM) lung disease.

A clinical hold is a notification issued by FDA to the sponsor to delay a proposed clinical trial or suspend an ongoing clinical trial. The company has been informed by FDA that this decision was based on an initial review of the interim results of a long-term rat inhalation carcinogenicity study, recently reported to the agency by Insmed, with ARIKACE. In this study, rats received daily doses of ARIKACE by inhalation for up to two years.

FDA has requested additional information on ARIKACE and data from the rat study. Insmed anticipates being able to supply the currently requested information and data within the next 30 days.

As a result of the clinical hold, Insmed has suspended initiation of the ARIKACE phase 3 clinical trial programs, including the recruitment and enrollment of patients. To date, no patients have been dosed in the pending clinical trials. The clinical hold will remain in effect at least until FDA reviews the information and data that is provided by Insmed.

“We will work closely with FDA to provide the agency with all appropriate information and data required to expedite their review and evaluation,” said Timothy Whitten, President and CEO of Insmed. “Once FDA has completed its review, we can better assess the impact this clinical hold might have on our phase 3 clinical programs for ARIKACE in CF and NTM.” 

Source: Insmed Inc.

Aptalis Pharma, a global specialty pharmaceutical company focused on gastrointestinal diseases and cystic fibrosis (CF), today announced that the U.S. Food and Drug Administration (FDA) has approved a new strength of ZENPEP® (pancrelipase) Delayed-Release Capsules.

The new formulation will be offered in 25,000 units of lipase, the highest strength currently approved by the FDA. The 25,000-unit strength will give physicians yet another option in dosing patients with exocrine pancreatic insufficiency (EPI) caused by CF or other conditions, and could potentially reduce pill burden.

“Added to the recent FDA approval of the 3,000-unit dose, ZENPEP offers physicians and their patients the broadest range of dosing options, including the lowest and highest doses available, of any FDA-approved pancreatic enzyme product,” said Frank Verwiel, M.D., President and Chief Executive Officer, Aptalis Pharma. He noted that ZENPEP is the only pancreatic enzyme offered in six dosage strengths — 3,000, 5,000, 10,000, 15,000, 20,000 and 25,000 units of lipase — reflecting the company’s strong emphasis on research and development. “We believe the broad range of ZENPEP strengths can provide added convenience by helping patients reduce the number of capsules they take with every meal, while the precise dosing can aid in the management of their EPI.”

Verwiel noted that offering six even strengths of ZENPEP also reflects the Company’s commitment to patients with EPI. For patients with cystic fibrosis in particular, the Company also provides award-winning patient-support programs such as ZPoints (www.zenpep.com/site/cfpatient.aspx) and CareFirst for Life (www.carefirstforlife.com). The ZPoints program, which provides vitamins, supplements and other support for patients with CF, will be extended to include this new dosage strength as well as the recently approved 3,000-unit strength.

About Exocrine Pancreatic Insufficiency

Exocrine Pancreatic Insufficiency (EPI) is the inability to properly digest food due to a lack of digestive enzymes made by the pancreas. EPI can result from a number of diseases, including cystic fibrosis, pancreatic cancer, gastrointestinal surgery, and chronic pancreatitis. The FDA estimates that more than 200,000 Americans suffer from EPI. If left untreated, EPI causes malnutrition and, especially in CF patients, impaired growth in children, compromised immune response and shortened life expectancy.

About ZENPEP®

Aptalis manufactures and markets ZENPEP® (pancrelipase) Delayed-Release Capsules, an FDA-approved pancreatic enzyme product (PEP) indicated for the treatment of exocrine pancreatic insufficiency (EPI) due to cystic fibrosis or other conditions. This condition affects approximately 90% of patients with CF. ZENPEP is currently marketed only in the U.S.

Source: Aptalis Pharma news release