The Boomer Esiason Foundation

Category: Therapies

  • Pancreatic Enzyme Products May Benefit Cystic Fibrosis Patients with Malabsorption via CF News Today

    Via Cystic Fibrosis News Today

    After the Food and Drug Administration (FDA) issued rules requiring approval of pancreatic enzyme products (PEPs) in 2004, the cost and availability of the products added another hardship to the lives of cystic fibrosis patients, some of whom use PEPs to prevent uncomfortable and dangerous side effects from malabsorption of food.

    Only a handful of PEPs have since been approved by the FDA, with the first in 2009. Aptalis Pharma has actively pursued clinical studies to further approve two of its pancrelipase products, Zenpep (APT-1008) and Ultrase MT 20, for patients with cystic fibrosis. Both PEPs are delayed-release capsules, and the results of Aptalis’ Phase 3 clinical trials were released earlier in 2014.

    Ultrase MT 20 is a concoction of lipase, amylase, and protease in higher amounts than those found in Aptalis’ Ultrase MT 12 and 18 capsules. During the trial, a total of 31 cystic fibrosis patients with exocrine pancreatic insufficiency entered the first of two intervention periods, and 26 completed the the second intervention period. Participants were randomized to receive Ultrase MT 20 or placebo for six to seven days, then instructed to use the alternate treatment (placebo or Ultrase MT 20) for six to seven days after a four-day stabilization period.

    The primary outcome measure for the study was percent coefficient of fat absorption (CFA). Patients receiving MT 20 had a significantly higher coefficient (88.55% CFA) than patients receiving placebo (55.61% CFA). In the secondary outcome measures, Ultrase MT 20 significantly enhanced percent coefficient of nitrogen absorption.

    Zenpep, one of the first PEPs approved by the FDA, was evaluated in an open-label trial with 19 cystic fibrosis patients with exocrine pancreatic insufficiency. All patients completed the trial, which consisted of a four-day screening period, a seven-day dose stabilization period, and a seven-day treatment period.

    After one week, 68.4% of the children responded to treatment, with responders defined as those who had less than 30% fat content in their stool and showed no signs of malabsorption. After two weeks, 57.9% of patients were responders.

    The results of these studies show that although PEPs are less readily available and more expensive than they were previously, they may actually benefit patients with cystic fibrosis.

  • IFN-γ Found to Help Clear Lethal Bacteria in Cystic Fibrosis Infections via Bio News -TX

    SOURCE – BIO NEWS TEXAS

    Researchers at The Research Institute at Nationwide Children’s Hospital in Ohio are finding ways to boost immunity in cystic fibrosis patients. Colleagues in principal investigator Dr. Benjamin Kopp’s laboratory published a study in PLoS One that details the use of interferon gamma (IFN-γ) to stimulate autophagy in macrophages to clear Burkholderia cenocepacia infections. “[B. cenocepacia] can avoid the host immune response, and that’s where something like IFN-γ might work better than traditional antibiotics,” said Dr. Kopp in a news release.

    B. cenocepacia is a bacteria found in the earth that is usually nonthreatening. In 2-5% of cystic fibrosis patients, the bacteria colonizes the thick, sticky mucus in their airways and can spread into the bloodstream to cause sometimes-fatal widespread inflammation. Normally, macrophages, the immune system’s first defense against pathogens, are able to clear infections. In the case of B. cenocepacia, the bacteria actually replicates inside macrophages. Adding to the problem is that “B. cenocepacia is multi-drug resistant, so usually when patients are ill, they are on a cocktail of antibiotics,” said Dr. Kopp. Antibiotics are not enough to fight the infection, and the infection deems patients unsuitable for lung transplants.

    Dr. Kopp’s team turned to the cytokine IFN-γ, which can be produced by neutrophils studied previously in unrelated work from UT Southwestern Medical Center as well as other cells, as a means of stimulating autophagy in infected macrophages. Autophagy is defective in cells from cystic fibrosis patients, and the team obtained macrophages from the blood of cystic fibrosis and non-cystic fibrosis patients. After infecting the cells with B. cenocepacia, the team noticed intrinsic IFN-γ production decreased in cystic fibrosis macrophages. To rescue the deficiency, the team treated cells with synthetic IFN-γ, and markers of autophagy increased with a concurrent decrease in infection.

    “The goal of the study was to show if you could stimulate autophagy, you could help clear pathogens better. These findings clearly suggest that is indeed the case,” said Dr. Kopp. But the work does not stop here. This study is only one of a series from Dr. Kopp’s laboratory that is looking a autophagy mediation, as it is becoming more prominent in cystic fibrosis and compromised immune system research. “As we’re learning more about CF, we’re finding more and more issues with the immune system and not just the typical clearance of mucus,” said Dr. Kopp. “Now we’re discovering that there is this initial response, of which autophagy is a part, in which the immune system is not clearing the bacteria and there are some continued deficits in that in CF patients.”

    IFN-γ has been extensively implicated in multiple sclerosis treatment, so it would be relatively easy to attempt clinical trials using IFN-γ in cystic fibrosis patients. If more treatments come from Dr. Kopp’s work, the cystic fibrosis community will be greatly benefited, as most available drugs are not fully effective and are accompanied by adverse effects to the point that physicians are unwilling to prescribe them.

  • Alcresta Announces Agreement with CFF Therapeutics to Develop Point-of-Care Nutritional Products

    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

  • Kamada Ltd. Launching New CF Clinical Trial this Summer

    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

  • CFF Therapeutics Extends Drug Development Collaboration via CFF.org

    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 

  • U.S. FDA Approves KALYDECO™ for Use in Eight Additional CF Mutations

    SOURCE – VERTEX PRESS RELEASE 

    • KALYDECO is the first medicine to treat the underlying cause of CF for people with specific mutations in the CFTR gene
    • KALYDECO facilitates increased chloride transport by potentiating the channel-open probability (or gating) of the CFTR protein
    • The eight additional mutations are present in approximately 150 people ages six and older in the United States

    BOSTON –(BUSINESS WIRE)– Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced the U.S. Food and Drug Administration (FDA) approved a supplemental New Drug Application (sNDA) for KALYDECOTM (ivacaftor) for people with cystic fibrosis (CF) ages 6 and older who have one of eight additional mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. KALYDECO was first approved in January 2012 for people with CF ages 6 and older who have at least one copy of the G551D mutation. With the approval of the sNDA, KALYDECO is now approved for use in people with CF with the following nine mutations: G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P and G1349D. In the United States, approximately 150 people ages 6 and older have one of the additional eight mutations for which KALYDECO is now approved.

    CF is caused by defective or missing CFTR proteins that result from mutations in the CFTR gene. The defective function or absence of CFTR proteins in people with CF results in poor flow of salt and water into and out of the cell in a number of organs, including the lungs. Ivacaftor facilitates increased chloride transport by potentiating the channel-open probability (or gating) of the CFTR protein.

    “We believe that KALYDECO has the potential to help more people with CF, and today’s approval is an important step toward that goal,” said Robert Kauffman, M.D. Ph.D., Senior Vice President and Co-Chief Medical Officer at Vertex. “As we progress over the coming year, we look forward to data from multiple other ongoing studies that are designed to evaluate whether additional people with CF may benefit from KALYDECO.”

    KALYDECO was granted Breakthrough Therapy designation by the U.S. FDA in late 2012. The sNDA approval is based on previously announced data from a Phase 3, two-part, randomized, double-blind, placebo-controlled, cross-over study of 39 people with CF who had one of the following mutations: G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, G1349D or G970R. The study showed statistically significant improvements in lung function (FEV1) for people in the overall study population who received ivacaftor, and the safety profile was similar to prior Phase 3 studies in people with the G551D mutation. Based on data from four patients with the G970R mutation enrolled in the study, the efficacy of KALYDECO in patients with the G970R mutation could not be established to support approval in the U.S. Vertex estimates that approximately 10 people with CF have the G970R mutation worldwide, including two people in the United States.

    Data from the study noted above were also used to support regulatory submissions in Europe, Canada and Australia for approval of KALYDECO in additional people with CF ages 6 and older. In Europe and Australia, approximately 250 people with CF have these additional mutations.

    SOURCE – VERTEX PRESS RELEASE 

  • FDA Advisory Committee supports the use of Novartis inhalation powder, Tobramycin

    The FDA Advisory Committee voted 13 to 1 that research showed adequate evidence to support the use of tobramycin inhalation powder by cystic fibrosis patients whose lungs contain the bacteria Pseudomonas aeruginosa, the leading cause of lung function loss in patients with CF. Tobramycin inhalation powder (TIP) is intended for CF patients over the age of six whose lung function is within a specific range. Currently, TIP is approved in 38 countries.

    To learn more about TIP, please see the Novartis Press Release.  

  • Gene Network Restores Cystic Fibrosis Protein Function

    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

  • Final Results from Phase 2 Combination Study of Kalydeco and VX-809 Show Significant Improvements

    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

  • Concentrated Saline Therapy Not Effective in Young Children with CF, Study Finds

    Inhaling concentrated saline (salt water) mist does not reduce how often infants and young children with cystic fibrosis need antibiotics for respiratory symptoms, according to findings from a clinical trial sponsored by the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health. This trial is the largest study of concentrated, or hypertonic, saline therapy in infants and preschoolers.

    Previous findings have shown that hypertonic saline provides some benefits to adults and older children with CF. The saline mist appears to loosen the thick mucus that builds up in the lungs and may reduce the recurrent infections, known as pulmonary exacerbations, which are thought to contribute to the lung damage and respiratory failure associated with CF. Based on these 2006 findings, the use of hypertonic saline in younger children has been rising. About 1 in 5 children under 6 years old with CF currently use this therapy, but without any clear evidence that it is effective in these children.

    “Even reasonably simple and non-toxic therapies can be burdensome, especially for families of small children with a chronic disease such as cystic fibrosis,” said Susan Shurin, M.D., acting director of the NHLBI, and a pediatrician. “This is one more study that illustrates the importance of conducting clinical research in children because medicine is not one size fits all — therapies that benefit adults or even teenagers do not always benefit younger children in the same way.”

    Results of the Infant Study of Inhaled Saline (ISIS) clinical trial was published online May 20 in the Journal of the American Medical Association. The findings were presented on the same date at the American Thoracic Society Annual Meeting in San Francisco.

    This pediatric study of hypertonic saline therapy enrolled 321 participants aged 4 months to 60 months at 30 CF care centers across the United States and Canada. The participants inhaled either 7 percent hypertonic saline, or a 0.9 percent saline mist as a control, twice daily for 48 weeks.

    Overall, the hypertonic saline was well-tolerated and side effects were minimal. However, there was no difference between the two saline groups in the rate of acute lung problems that required treatment with antibiotics (average of 2.3 cases per participant per year in each group). Hypertonic saline also did not improve other clinical measurements such as coughing, respiratory rate, height, or weight. CF can stunt the growth of children.

    The study authors noted that CF complications in infants and young children generally have different origins than complications in adults and older children; for instance, young children develop more viral, as opposed to bacterial, infections. These differences in complications might account for the lack of effectiveness of the hypertonic saline in reducing antibiotic use in children.

    Early lung damage associated with CF frequently shows no clinical symptoms. Whether hypertonic saline treatment in infants and young children could still slow the progression of airway damage, resulting in better lung function later, is not known.

    CF is an inherited disorder that results in a buildup of thick and sticky mucus in the lungs, airway, and other organs. The excess mucus in the lungs can lead to coughing, breathing problems, and increased risk of lung infections. There is no cure, although advances in treatments have improved both the length and quality of life of people with this disease.

    Learn more about the ISIS Trial at: http://clinicaltrials.gov/ct2/show/NCT00709280