The American Thoracic Society has released new clinical guidelines for the treatment of exacerbations in cystic fibrosis based on a review of the literature on current clinical practices.
“This is the first such comprehensive and evidence-based systematic review of best practices for pulmonary exacerbation of cystic fibrosis,” said Susanna McColley, M.D., head of the division of pulmonary medicine and director of the Cystic Fibrosis Center at Children’s Memorial Hospital and associate professor at Northwestern University’s Feinberg School of Medicine. “Until these, guidelines were arrived at by a less rigorous process based on the consensus of a committee of experts.”
When cystic fibrosis patients suffer an acute exacerbation, they undergo an acute worsening of symptoms, which typically require medical intervention. While a prospective definition of an exacerbation has not yet been developed, clinical features are generally well-defined and represent a sharp deterioration in the general condition of the patient, often involving systemic symptoms such as weight loss and lack of appetite, as well as worsening of pulmonary symptoms such as cough, sputum production and shortness of breath. Exacerbations are the most common reason for hospitalization of cystic fibrosis patients.
The guidelines, which were presented at the North American Cystic Fibrosis Conference in October, highlighted a number of common practices in cystic fibrosis exacerbations.
The committee gave guidance on two areas of significant interest to clinicians: synergy testing and the dosing of aminoglycoside antibiotics. In the case of synergy testing—a costly and time-consuming practice of determining what synergistic effects different antibiotics may have when used together against multi-drug resistant infections—was found to have little benefit to the patient and the committee recommended against the routine use of it. In the case of aminoglycoside antibiotics, they found that three-times-daily dosing was no more effective than once-daily dosing and recommended once-daily dosing in most cases.
The committee also affirmatively recommended continuation of two current practices—continuing chronic therapies during exacerbation treatment and airway clearance therapies—both of which were found to have moderate benefits to the patient.
Perhaps most strikingly, the committee found that in six of ten investigated practices, there was simply not enough data to recommend for or against them. “This highlights that there are a lot of unanswered questions,” said Dr. McColley, citing the need for research that would clarify whether there are different outcomes associated with the practices, which included inpatient versus outpatient care; simultaneous use of intravenous and inhaled antibiotics; number of antibiotics used to treat Pseudomonas aeruginosa; continuous infusion of betalactam antibiotics; and duration of antibiotic treatment.
“We have incomplete information, but the guidelines provide important guidance to physicians, patients, third party payers on the treatment of this serious and common complication of CF respiratory disease,” she said. “By reducing variability in practice, implementation of these guidelines may help to improve outcomes of care.”
More information: http://www.thoracic.org/sections/publications/press-releases/resources/110109-cf-guidelines.pdf
The American Thoracic Society has released new clinical guidelines for the treatment of exacerbations in cystic fibrosis based on a review of the literature on current clinical practices.
“This is the first such comprehensive and evidence-based systematic review of best practices for pulmonary exacerbation of cystic fibrosis,” said Susanna McColley, M.D., head of the division of pulmonary medicine and director of the Cystic Fibrosis Center at Children’s Memorial Hospital and associate professor at Northwestern University’s Feinberg School of Medicine. “Until these, guidelines were arrived at by a less rigorous process based on the consensus of a committee of experts.”
When cystic fibrosis patients suffer an acute exacerbation, they undergo an acute worsening of symptoms, which typically require medical intervention. While a prospective definition of an exacerbation has not yet been developed, clinical features are generally well-defined and represent a sharp deterioration in the general condition of the patient, often involving systemic symptoms such as weight loss and lack of appetite, as well as worsening of pulmonary symptoms such as cough, sputum production and shortness of breath. Exacerbations are the most common reason for hospitalization of cystic fibrosis patients.
The guidelines, which were presented at the North American Cystic Fibrosis Conference in October, highlighted a number of common practices in cystic fibrosis exacerbations.
The committee gave guidance on two areas of significant interest to clinicians: synergy testing and the dosing of aminoglycoside antibiotics. In the case of synergy testing—a costly and time-consuming practice of determining what synergistic effects different antibiotics may have when used together against multi-drug resistant infections—was found to have little benefit to the patient and the committee recommended against the routine use of it. In the case of aminoglycoside antibiotics, they found that three-times-daily dosing was no more effective than once-daily dosing and recommended once-daily dosing in most cases.
The committee also affirmatively recommended continuation of two current practices—continuing chronic therapies during exacerbation treatment and airway clearance therapies—both of which were found to have moderate benefits to the patient.
Perhaps most strikingly, the committee found that in six of ten investigated practices, there was simply not enough data to recommend for or against them. “This highlights that there are a lot of unanswered questions,” said Dr. McColley, citing the need for research that would clarify whether there are different outcomes associated with the practices, which included inpatient versus outpatient care; simultaneous use of intravenous and inhaled antibiotics; number of antibiotics used to treat Pseudomonas aeruginosa; continuous infusion of betalactam antibiotics; and duration of antibiotic treatment.
“We have incomplete information, but the guidelines provide important guidance to physicians, patients, third party payers on the treatment of this serious and common complication of CF respiratory disease,” she said. “By reducing variability in practice, implementation of these guidelines may help to improve outcomes of care.”
More information: http://www.thoracic.org/sections/publications/press-releases/resources/110109-cf-guidelines.pdf
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09.09.2009
US-based clinical-stage biopharmaceutical company Mpex Pharmaceuticals Inc reported today favourable data from its Phase IIb study of Aeroquin (a novel aerosol formulation of levofloxacin,
MP-376) in cystic fibrosis.
Data showed that nebulised Aeroquin met the primary endpoint of reducing bacterial counts of Pseudomonas aeruginosa (P. aeruginosa) in sputum after 28 days of dosing versus placebo. Clinically and statistically significant improvements versus placebo were also seen in a number of important clinical endpoints, including FEV1, percent predicted FEV1, FEF25-75 (all measures of respiratory function) and time to need for anti-pseudomonal antibiotics (a measure of exacerbations). Both once and twice-daily dosing of Aeroquin showed activity in this trial, with higher doses showing improved responses. Aeroquin was well tolerated and no significant change in antibiotic resistance was observed in this study.
The Phase IIb, multi-centre randomised, double-blind, placebo-controlled trial (Mpex 204) studied 151 CF patients to evaluate the safety, tolerability and efficacy of inhaled Aeroquin administered for 28 days using an Investigational eFlow Nebulizer System (PARI Pharma GmbH). Patients were then followed for an additional 28 days after completion of dosing. The trial was conducted in the United States, Germany and the Netherlands.
US-based clinical-stage biopharmaceutical company Mpex Pharmaceuticals Inc reported today favourable data from its Phase IIb study of Aeroquin (a novel aerosol formulation of levofloxacin,
MP-376) in cystic fibrosis.
Data showed that nebulised Aeroquin met the primary endpoint of reducing bacterial counts of Pseudomonas aeruginosa (P. aeruginosa) in sputum after 28 days of dosing versus placebo. Clinically and statistically significant improvements versus placebo were also seen in a number of important clinical endpoints, including FEV1, percent predicted FEV1, FEF25-75 (all measures of respiratory function) and time to need for anti-pseudomonal antibiotics (a measure of exacerbations). Both once and twice-daily dosing of Aeroquin showed activity in this trial, with higher doses showing improved responses. Aeroquin was well tolerated and no significant change in antibiotic resistance was observed in this study.
The Phase IIb, multi-centre randomised, double-blind, placebo-controlled trial (Mpex 204) studied 151 CF patients to evaluate the safety, tolerability and efficacy of inhaled Aeroquin administered for 28 days using an Investigational eFlow Nebulizer System (PARI Pharma GmbH). Patients were then followed for an additional 28 days after completion of dosing. The trial was conducted in the United States, Germany and the Netherlands.
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10.09.2009
Solvay Pharmaceuticals, Inc. announced today that Phase III data published in the Journal of Cystic Fibrosis showed that CREON® (pancrelipase) Delayed-Release Capsules, the most prescribed pancreatic enzyme replacement therapy (PERT) in the United States, significantly improves a key measure of fat absorption in patients with CF who suffer from exocrine pancreatic insufficiency (EPI). EPI is a condition resulting from a deficiency in the production and/or secretion of pancreatic enzymes that are necessary to digest nutrients in food and, if untreated, can lead to poor growth, poor weight gain and failure to thrive in children with CF.
According to the study results, patients with CF and confirmed EPI had an improved coefficient of fat absorption (CFA) during treatment with CREON® compared to treatment with placebo. CFA is calculated based on measures of fat ingestion and fat excretion; assessing the CFA of a patient is a way to measure the absorption of fat as a percentage of fat intake in patients being tested for EPI. The trial reached statistical significance on its primary endpoint, which was CFA.
“These study results demonstrate that CREON® is effective in decreasing the maldigestion and malabsorption associated with pancreatic insufficiency in patients with cystic fibrosis,” said Bruce C. Trapnell, MD, Professor of Medicine and Pediatrics at the University of Cincinnati and Cincinnati Children’s Hospital Medical Center. “Patients enrolled in this study had poor fat absorption without treatment, which is commonly associated with uncomfortable gastrointestinal symptoms and severe malnutrition. In addition to the impressive increase in fat absorption demonstrated in these individuals, the secondary outcomes of the study have important implications for those involved in the care of these patients.”
CREON® was approved by the Food and Drug Administration (FDA) with an indication to treat EPI due to CF or other conditions based on the results of this clinical study. As the first FDA-approved PERT, CREON® was also the first product in the class to provide a Medication Guide with important dosing information, including instructions for administration to infants and toddlers, which is consistent with the CF Foundation Consensus Conference Guidelines.
Study Details
The double-blind, randomized, placebo-controlled two-arm, crossover study examined the efficacy and safety of CREON® (Pancrelipase) Delayed-Release 24,000 lipase unit capsules in subjects aged 12 years or older with EPI due to CF. EPI was confirmed in all subjects by a CFA of
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09.21.2009
Researchers at the University of North Carolina at Chapel Hill have discovered a genetic risk factor for severe liver disease in people with cystic fibrosis. Those who carry a particular variant of the SERPINA1 gene (also known as alpha-1-antitrypsin or alpha-1-antiprotease) are five times more likely to develop cirrhosis and other liver complications than patients who carry the normal version of the gene.
The study, which appears in the Sept. 9 issue of the Journal of the American Medical Association (JAMA), could lead to earlier detection and diagnosis of cystic fibrosis liver disease and better treatment options for the patients affected by the disease. In addition, it could pave the way for similar studies in more common forms of liver disease.
“I predict that as we uncover more risk factors of liver disease in cystic fibrosis we may also find that they play a role in how rapidly people with a more common malady, such as viral hepatitis, develop liver complications (or “fibrosis”),” said senior study author Michael R. Knowles, M.D., professor of pulmonary and critical care medicine at UNC.
Cystic fibrosis is the most common fatal genetic illness among Caucasians. In the disease, defects in the CFTR gene cause the lungs, intestines and pancreas to become clogged with mucus, resulting in breathing problems and other difficulties. Though every patient with cystic fibrosis carries mutations in both copies of their CFTR gene (one inherited from the mother and one from the father), symptoms can vary widely from patient to patient. For instance, about five percent of cystic fibrosis patients develop liver disease so severe it requires a liver transplant.
For the last decade, researchers have been investigating what other genetic factors might modify the effects of the disease-causing mutations in the CFTR gene, further altering the biological conditions under which the disease unfolds to either make it milder or more severe. Several genes have emerged as potential “genetic modifiers,” and studies to replicate some of those findings have recently been accomplished.
In this study, the UNC researchers collaborated with an international team of scientists to compile the largest number of samples ever from cystic fibrosis patients with severe liver disease. The study was initially conducted in 124 cystic fibrosis patients with severe liver disease and 843 cystic fibrosis patients without liver disease. The team evaluated nine sequence variants in five genes that previous studies had suggested might be associated with liver disease.
They found that more cystic fibrosis patients with liver disease had a particular version of the SERPINA1 gene—called the Z allele – than patients without liver disease, indicating that the gene variant plays a role in the development of this ailment. The researchers confirmed their results in a separate set of cystic fibrosis patients, 136 with liver disease and 1088 without.
According to lead study author Jaclyn R. Bartlett, Ph.D., discovering such risk factors will enable clinicians to identify cystic fibrosis patients who may be predisposed to develop liver disease. “We also hope that further research will show how the presence of this particular gene affects the liver on a molecular level in cystic fibrosis patients,” said Bartlett, a research associate scientist at UNC.
Aided by their international collaborators, the researchers are now searching for genetic modifiers associated with other complications of cystic fibrosis, including lung disease, intestinal obstruction and diabetes.
Researchers at the University of North Carolina at Chapel Hill have discovered a genetic risk factor for severe liver disease in people with cystic fibrosis. Those who carry a particular variant of the SERPINA1 gene (also known as alpha-1-antitrypsin or alpha-1-antiprotease) are five times more likely to develop cirrhosis and other liver complications than patients who carry the normal version of the gene.
The study, which appears in the Sept. 9 issue of the Journal of the American Medical Association (JAMA), could lead to earlier detection and diagnosis of cystic fibrosis liver disease and better treatment options for the patients affected by the disease. In addition, it could pave the way for similar studies in more common forms of liver disease.
“I predict that as we uncover more risk factors of liver disease in cystic fibrosis we may also find that they play a role in how rapidly people with a more common malady, such as viral hepatitis, develop liver complications (or “fibrosis”),” said senior study author Michael R. Knowles, M.D., professor of pulmonary and critical care medicine at UNC.
Cystic fibrosis is the most common fatal genetic illness among Caucasians. In the disease, defects in the CFTR gene cause the lungs, intestines and pancreas to become clogged with mucus, resulting in breathing problems and other difficulties. Though every patient with cystic fibrosis carries mutations in both copies of their CFTR gene (one inherited from the mother and one from the father), symptoms can vary widely from patient to patient. For instance, about five percent of cystic fibrosis patients develop liver disease so severe it requires a liver transplant.
For the last decade, researchers have been investigating what other genetic factors might modify the effects of the disease-causing mutations in the CFTR gene, further altering the biological conditions under which the disease unfolds to either make it milder or more severe. Several genes have emerged as potential “genetic modifiers,” and studies to replicate some of those findings have recently been accomplished.
In this study, the UNC researchers collaborated with an international team of scientists to compile the largest number of samples ever from cystic fibrosis patients with severe liver disease. The study was initially conducted in 124 cystic fibrosis patients with severe liver disease and 843 cystic fibrosis patients without liver disease. The team evaluated nine sequence variants in five genes that previous studies had suggested might be associated with liver disease.
They found that more cystic fibrosis patients with liver disease had a particular version of the SERPINA1 gene—called the Z allele – than patients without liver disease, indicating that the gene variant plays a role in the development of this ailment. The researchers confirmed their results in a separate set of cystic fibrosis patients, 136 with liver disease and 1088 without.
According to lead study author Jaclyn R. Bartlett, Ph.D., discovering such risk factors will enable clinicians to identify cystic fibrosis patients who may be predisposed to develop liver disease. “We also hope that further research will show how the presence of this particular gene affects the liver on a molecular level in cystic fibrosis patients,” said Bartlett, a research associate scientist at UNC.
Aided by their international collaborators, the researchers are now searching for genetic modifiers associated with other complications of cystic fibrosis, including lung disease, intestinal obstruction and diabetes.
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12.10.2009
Gilead Sciences Inc. today announced that the Anti-Infective Drugs Advisory Committee of the U.S. Food and Drug Administration (FDA) has recommended that aztreonam for inhalation solution be approved for the treatment of infections due to Pseudomonas aeruginosa (P. aeruginosa) in patients with cystic fibrosis (CF). The committee voted 15 to 2 that Gilead has provided sufficient evidence of the safety and efficacy of aztreonam for inhalation solution. The panel also voted 17 to 0 that aztreonam for inhalation solution 75 mg three times daily is a correct dose and regimen.
The recommendations of the Advisory Committee are not binding but will be considered by the FDA as the agency completes its review of Gilead’s application. The FDA has established a target review date, under the Prescription Drug User Fee Act (PDUFA), of February 13, 2010. In the interim, Gilead will continue to make the product available through its Expanded Access Program in the United States.
“Effectively treating infections in patients with CF is very challenging, and new treatment options are urgently needed,” said Norbert Bischofberger, PhD, Executive Vice President, Research and Development and Chief Scientific Officer, Gilead Sciences. “We will continue to work closely with the FDA as it completes its review of aztreonam for inhalation solution.”
CF is a chronic, debilitating genetic disease that affects the respiratory and digestive systems of approximately 70,000 people worldwide. Chronic pulmonary infections due to P. aeruginosa are the single greatest cause of morbidity and mortality among patients with CF.
Gilead originally submitted the NDA for the potential product in November 2007. In September 2009, the product was granted conditional marketing approval in Canada and the European Union under the trade name Cayston(R) (aztreonam lysine 75 mg powder and solvent for nebuliser solution). Applications for marketing approval of Cayston are also pending in Australia, Switzerland and Turkey.
About Aztreonam for Inhalation Solution
Aztreonam for inhalation solution is an antibiotic candidate for people with cystic fibrosis who have P. aeruginosa. Aztreonam has potent in vitro activity against Gram-negative bacteria such as P. aeruginosa. Aztreonam formulated with arginine is an FDA-approved agent for intravenous administration for treating various infections. Aztreonam formulated with lysine is a proprietary formulation of aztreonam developed specifically for inhalation. It has been designated with orphan drug status in the United States and European Union.
In the United States, aztreonam for inhalation solution has not yet been determined by the FDA to be safe or efficacious in humans for its ultimate intended use.
Gilead Sciences Inc. today announced that the Anti-Infective Drugs Advisory Committee of the U.S. Food and Drug Administration (FDA) has recommended that aztreonam for inhalation solution be approved for the treatment of infections due to Pseudomonas aeruginosa (P. aeruginosa) in patients with cystic fibrosis (CF). The committee voted 15 to 2 that Gilead has provided sufficient evidence of the safety and efficacy of aztreonam for inhalation solution. The panel also voted 17 to 0 that aztreonam for inhalation solution 75 mg three times daily is a correct dose and regimen.
The recommendations of the Advisory Committee are not binding but will be considered by the FDA as the agency completes its review of Gilead’s application. The FDA has established a target review date, under the Prescription Drug User Fee Act (PDUFA), of February 13, 2010. In the interim, Gilead will continue to make the product available through its Expanded Access Program in the United States.
“Effectively treating infections in patients with CF is very challenging, and new treatment options are urgently needed,” said Norbert Bischofberger, PhD, Executive Vice President, Research and Development and Chief Scientific Officer, Gilead Sciences. “We will continue to work closely with the FDA as it completes its review of aztreonam for inhalation solution.”
CF is a chronic, debilitating genetic disease that affects the respiratory and digestive systems of approximately 70,000 people worldwide. Chronic pulmonary infections due to P. aeruginosa are the single greatest cause of morbidity and mortality among patients with CF.
Gilead originally submitted the NDA for the potential product in November 2007. In September 2009, the product was granted conditional marketing approval in Canada and the European Union under the trade name Cayston(R) (aztreonam lysine 75 mg powder and solvent for nebuliser solution). Applications for marketing approval of Cayston are also pending in Australia, Switzerland and Turkey.
About Aztreonam for Inhalation Solution
Aztreonam for inhalation solution is an antibiotic candidate for people with cystic fibrosis who have P. aeruginosa. Aztreonam has potent in vitro activity against Gram-negative bacteria such as P. aeruginosa. Aztreonam formulated with arginine is an FDA-approved agent for intravenous administration for treating various infections. Aztreonam formulated with lysine is a proprietary formulation of aztreonam developed specifically for inhalation. It has been designated with orphan drug status in the United States and European Union.
In the United States, aztreonam for inhalation solution has not yet been determined by the FDA to be safe or efficacious in humans for its ultimate intended use.
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09.11.2009
Mpex Pharmaceuticals, a biopharmaceutical company, has reported positive data from its Phase IIb clinical trial with Aeroquin, a novel aerosol formulation of levofloxacin, MP-376 in cystic fibrosis.
According to Mpex Pharmaceuticals, trial results showed that nebulized Aeroquin met the primary endpoint of reducing bacterial counts of Pseudomonas aeruginosa in sputum after 28 days of dosing versus placebo. Clinically and statistically significant improvements compared to placebo were also seen in a number of important clinical endpoints, including FEV1, percent predicted FEV1, FEF25-75 and time to need for anti-pseudomonal antibiotics. Both once and twice-daily dosing of Aeroquin showed activity in this trial, with higher doses showing improved responses. Aeroquin was well tolerated and no significant change in antibiotic resistance was observed in this study, the company said.
The Phase IIb, multi-center randomized, double-blind, placebo-controlled trial (Mpex 204) studied 151 cystic fibrosis patients to evaluate the safety, tolerability and efficacy of inhaled Aeroquin administered for 28 days using an investigational eFlow nebulizer system. Patients were then followed for an additional 28 days after completion of dosing. The trial was conducted in the US, Germany and the Netherlands.
Daniel Burgess, President and CEO of Mpex, said: “We thank the participating CF patients and physicians for helping make this trial a success. We are eager to meet with CF experts and regulatory authorities in the U.S. and Europe to discuss these results and determine the most expeditious path to move Aeroquin through Phase III development.”
Mpex Pharmaceuticals, a biopharmaceutical company, has reported positive data from its Phase IIb clinical trial with Aeroquin, a novel aerosol formulation of levofloxacin, MP-376 in cystic fibrosis.
According to Mpex Pharmaceuticals, trial results showed that nebulized Aeroquin met the primary endpoint of reducing bacterial counts of Pseudomonas aeruginosa in sputum after 28 days of dosing versus placebo. Clinically and statistically significant improvements compared to placebo were also seen in a number of important clinical endpoints, including FEV1, percent predicted FEV1, FEF25-75 and time to need for anti-pseudomonal antibiotics. Both once and twice-daily dosing of Aeroquin showed activity in this trial, with higher doses showing improved responses. Aeroquin was well tolerated and no significant change in antibiotic resistance was observed in this study, the company said.
The Phase IIb, multi-center randomized, double-blind, placebo-controlled trial (Mpex 204) studied 151 cystic fibrosis patients to evaluate the safety, tolerability and efficacy of inhaled Aeroquin administered for 28 days using an investigational eFlow nebulizer system. Patients were then followed for an additional 28 days after completion of dosing. The trial was conducted in the US, Germany and the Netherlands.
Daniel Burgess, President and CEO of Mpex, said: “We thank the participating CF patients and physicians for helping make this trial a success. We are eager to meet with CF experts and regulatory authorities in the U.S. and Europe to discuss these results and determine the most expeditious path to move Aeroquin through Phase III development.”
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