CF.www.NEWS

May 17, 2006
Chiron Dealt Blow Over Cystic Fibrosis Treatment

In a setback for biopharmaceutical company Chiron Corp., a federal judge has ruled that the company's medical-method patent covering a drug-device combination used by cystic fibrosis victims cannot be used to bar use of the treatment in lower concentrations.

The patent at issue in the case, U.S. Patent No. 6,890,907, covers a method of treating lung infections by using certain concentrations of liquid tobramycin with high-efficiency nebulizers.

The method is aimed at treating patients suffering from cystic fibrosis, a debilitating disease that manifests in early childhood and causes mucus buildup in the airways, drastically shortening the
life expectancy of victims.

Inhaled antibiotics such as tobramycin have long been used to treat pulmonary lung infections.

According to court documents, a drug-device combination using tobramycin with a particular nebulizer came on the market in 1997. Chiron later acquired the method and successfully marketed it as TOBI, which became the leading treatment on the market for pulmonary infections in cystic fibrosis patients.

However, the method had substantial drawbacks, including lengthy treatment time and unportability, prompting several companies - excluding Chiron - to begin developing higher efficiency nebulizers in the late 1990s, according to court documents.

The new nebulizers cut the treatment duration at least in half, encouraging children to comply with their treatment regimens, and are small and portable, unlike the heavy TOBI machine.

Despite these developments, however, Chiron has not come out with a new drug-device combination using a new nebulizer and has instead continued to promote TOBI, which enjoys a dominant market position, according to court documents. Under FDA regulations, TOBI can only be sold with older nebulizer versions.

Chiron's medical-method patent aimed to prevent the new generation of nebulizers from being used with tobramycin, or at least from using those treatment methods within the limits of the claims.

In May 2005, Chiron brought charges against a group of compounding pharmacies and distributors—SourceCF Inc., Maxor National Pharmacy Services Corporation (IV Solutions), Foundation Care LLC, and Pharmaceutical Specialities Inc- alleging the companies infringed on the `907 patent by selling a product called the eFlow inhaler and instructing doctors and cystic fibrosis victims on how to use it.

At the time when Chiron obtained the '907 patent, the compounding pharmacists were dispensing concentrations of tobramycin of 100 mg/ml for use in the eFlow device.
During settlement negotiations, it was agreed that such a concentration of tobramycin fell within the claims of the '907 patent, and the pharmacy defendants stopped filling prescriptions for concentrations of 100 mg/ml.

In December 2005, the court granted a permanent injunction enjoining the defendants from selling any tobramycin formulation at concentrations between 60 mg/ml and 200 mg/ml, although the pharmacy defendants had already shifted to dispensing concentrations of 40 mg/ml and 50 mg/ml tobramycin for use in the eFlow device, according to court documents. Chiron then contended that even concentrations of 50 mg/ml or less violated the patent.

Following a bench trial, U.S. District Judge William Alsup has now ruled that concentrations of 50 mg/ml or less do not infringe the '907 patent, although he noted in court documents that the order does not address the potential invalidity of the '907 patent.

"Chiron's patent does not cover the weaker concentrations at issue in this suit," stated Judge Alsup in his order. "It is true that the lower concentrations seem safe and efficacious. But the patent is limited by the concentrations actually claimed. The patent does not go so far as to claim all safe and effective doses regardless of concentration."

According to Richard P. Doyle, Jr. of Janssen Doyle LLP, the firm representing the defendants in the case, the ruling marks a huge victory for patients and potentially huge losses for Chiron by allowing doctors to prescribe the eFlow nebulizer manufactured by PARI.

"This is a rape and pillaging case on the part of Chiron," said Doyle. "I've never run into somebody so evil. Chiron spent millions of dollars to keep this new technology off the market simply because it would hurt sales." Doyle said Chiron may appeal, but the company "has lost on so many grounds that it'll be a problem." "At this point, the case is over, and we've won," he said. "Children can continue to get the medicine they need."

Mike Walters, president and CEO of SourceCF, said the company was very pleased with the court's finding. "We find comfort in the fact that patients who have been prescribed tobramycin with eFlow in these concentrations can continue to realize its benefits," he said in a statement.

This is the second lawsuit brought by Chiron against SourceCF over the eFlow nebulizer. The first lawsuit was settled last year after Chiron obtained a temporary restraining order barring the defendants from making false statements.

Mark D. Petersen, partner at Farella Braun & Martel LLP, one of two firms representing Chiron (now Novartis) in the case, said it is important to note the permanent injunction achieved by Chiron last December and the fact that SourceCF changed its product as a result of that injunction. "Chiron, now Novartis, is considering its appellate rights and its future course of action," said Petersen, adding that TOBI is the only existing FDA-approved product for the treatment of cystic fibrosis. Kaye Scholer, the second firm representing Chiron in the case, declined to comment on the ruling. Founded in 1981, Chiron is the third-oldest biotechnology company after industry leaders Amgen Inc. and Genentech Inc. It was aquired by drug maker Novartis AG last year in a $5.1 billion takeover.

The latest suit is not the first time Chiron has been in court over tobramycin. In October 2003, Chiron and Children's Hospital and Regional Medical
Center of Seattle settled a patent infringement suit against Roxane Laboratories, a subsidiary of Boehringer-Ingelheim Corporation, concerning Roxane's plans to market a generic equivalent of the drug.

Under the terms of the agreement, Roxane, which had previously withdrawn its application for approval of a generic equivalent of TOBI, agreed it would not seek approval to market the product until the expiration of the patent in 2014.

Chiron and Children's Hospital agreed to dismiss their infringement relief claims against Roxane, and Roxane dropped its challenge to the patent. The defendants are represented in the immediate matter by Janssen Doyle LLP. Chiron is represented by Kaye Scholer LLP and Farella Braun & Martel LLP.

The case is Chiron Corporation v. Sourcecf Inc. et al., case number 3:05-cv-01938-WHA, in the U.S. District Court for the Northern District of California.

Source: Yahoo Groups - Sharktank / Portfolio Media, New York

May 17, 2006
Press Release
Vertex Pharmaceuticals Initiates Phase I Development for VX-770 in Cystic Fibrosis
Wednesday

CAMBRIDGE, Mass.-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX - News) today announced that it has initiated a Phase I clinical study for VX-770, a novel, oral drug candidate that specifically targets a key mechanism underlying cystic fibrosis (CF). The study will evaluate the safety, tolerability and pharmacokinetics of escalating single and multiple doses of VX-770 in healthy volunteers, and also will evaluate single doses of VX-770 in patients with CF. The study is expected to enroll more than 50 individuals. In March 2006, Vertex and Cystic Fibrosis Foundation Therapeutics Inc. (CFFT) entered into a collaboration to accelerate clinical development of VX-770. CFFT is the nonprofit drug discovery and development affiliate of the Cystic Fibrosis Foundation. Vertex retains worldwide rights to develop and commercialize VX-770.

"This first clinical study for VX-770 signifies an important milestone in the productive collaborative history that we have shared with Vertex in the discovery of novel CF therapies," said Robert J. Beall, Ph.D., President and Chief Executive Officer of the Cystic Fibrosis Foundation and CFFT. "We believe that compounds such as VX-770 have great potential to change the course of CF, and we are pleased to support the accelerated development of VX-770 in early clinical studies."

"VX-770 is the first drug candidate to have emerged from our innovative CF research efforts, and the initiation of this Phase I study represents an exciting new stage in the development of this compound," said John Alam, M.D., Executive Vice President, Medicines Development, and Chief Medical Officer of Vertex. "Laboratory results for VX-770 have been highly encouraging and support the initiation of this first clinical study. We look forward to evaluating VX-770 in both healthy volunteers and patients with CF in the coming months to determine the next steps for the VX-770 development program."

Study Design

The Phase I study for VX-770 announced today is expected to enroll more than 50 individuals, including healthy volunteers and patients with CF. Dosing has been initiated in the first cohort of healthy volunteers, and is expected to progress to patients with CF later this year. Healthy volunteers in the Phase I study will receive escalating doses of VX-770 for treatment durations of up to 14 days, and patients with CF will receive single doses of VX-770.

Fast Track Designation for VX-770

Vertex also today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to VX-770. The FDA granted Fast Track designation to VX-770 for the following reasons:

VX-770 is intended to preserve pulmonary function, decrease morbidity, and prolong survival in patients with CF by decreasing cycles of mucus plugging, infection, and inflammation in the lungs.

Under the FDA Modernization Act of 1997, Fast Track designation indicates that the FDA will facilitate the development and may expedite the review of a drug if it is intended for the treatment of a serious or life-threatening condition and demonstrates the potential to address an unmet medical need for such a condition.

About VX-770

VX-770 was advanced into preclinical development based on a successful research collaboration with CFFT that incorporated capabilities and proprietary research from Vertex's San Diego research site. VX-770 may act to restore the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, the defective cell membrane protein responsible for the progression of CF. Defects in the CFTR protein affect the transport of chloride and other ions across cells, and lead to the accumulation of thick, sticky mucus in the lungs of patients with CF. This mucus fosters chronic infection and inflammation, and results in irreversible lung damage. Potentiator compounds such as VX-770 are designed to increase the probability that the CFTR channel is open, which could result in an increase in chloride transport across the cell surface in some patients. In laboratory experiments, using cells from patients with CF where CFTR proteins are present on the cell surface, VX-770 has restored the gating activity of defective CFTR channels.

Collaborative History with CFFT

Vertex initiated its CF research program in May 2000 in collaboration with CFFT, which offers special expertise and experience in CF drug discovery and development. Vertex and CFFT expanded the agreement in May 2004, and in March 2006, entered into a new collaboration for the accelerated development of VX- 770. Under the collaboration, CFFT will provide to Vertex approximately $13.3 million to support clinical development of VX-770 through the fourth quarter of 2007. In addition to the development collaboration for VX-770, in January 2006, Vertex and CFFT entered into an expanded research collaboration to discover novel compounds known as correctors, which may work by increasing the number of CFTR channels on the cell surface. To date, CFFT has provided to Vertex more than $40 million for CF research.

About Cystic Fibrosis and the Cystic Fibrosis Foundation

Cystic fibrosis is a genetic disease affecting approximately 30,000 people in the United States. A defect in the CFTR gene causes the body to produce abnormally thick, sticky mucus that leads to chronic, life-threatening lung infections and impairs digestion. When the CF Foundation was established in 1955, few children lived to attend elementary school. Today, because of research and care supported by the CF Foundation -- with money raised through donations from families, corporations and foundations -- the median predicted age of survival for people with CF is now more than 36 years.

The Cystic Fibrosis Foundation, headquartered in Bethesda, MD, is a donor-supported, nonprofit organization committed to finding therapies and ultimately a cure for CF, and to improving the lives of those with the disease. For more information on CF and the programs of the CF Foundation, call (800) FIGHT CF or visit http://www.cff.org.

Source: Vertex Pharmaceuticals Incorporated

May 10, 2006
Aradigm's cystic fibrosis drug candidate gets orphan status

Aradigm Corporation has received orphan drug designation from the FDA for a proprietary liposomal formulation of ciprofloxacin for the management of cystic fibrosis.

Aradigm's liposomal ciprofloxacin is an aerosolized formulation of this proven anti-infective drug that was designed to increase the drug's residence time in the lung and prolong its anti-infective properties in order to treat the related infections found in cystic fibrosis patients.

"This designation for liposomal ciprofloxacin provides us the opportunity to help accelerate our efforts behind this innovative product," said Dr Babatunde Otulana, senior vice president of clinical and regulatory affairs at Aradigm. "We appreciate the multiple financial and strategic benefits that this status provides us in developing this application for an area of unmet medical need."

Orphan drug designation is intended to encourage R&D of new therapies for diseases that affect fewer than 200,000 patients in the US. As a designated orphan drug, liposomal ciprofloxacin is eligible for tax credits based upon its clinical development costs, as well as assistance from the FDA in guiding the drug through the regulatory approval process. The designation also provides the opportunity to obtain market exclusivity for seven years from the date of NDA approval.

CF is a genetic disease affecting approximately 30,000 children and adults in the US and about 60,000 worldwide. The defective gene causes production of excess mucus that clogs the lungs and often leaves patients vulnerable to life-threatening lung infections.

January 18, 2006
Saltwater therapy helps ease cystic fibrosis

By Liz Szabo, USA TODAY

Australian surfers have helped inspire a new way to treat a deadly genetic disease.

Patients with cystic fibrosis, a rare disorder that damages the lungs, have reported feeling better after surfing, says Mark Elkins, a researcher at Sydney's Royal Prince Alfred Hospital. Surfers said their chests and sinuses felt clear, and they coughed up much of the thick mucus that clogs their lungs.

Doctors wondered why, Elkins says. Was it the exercise? Or was it the saltwater?

Scientists have known for years that salt plays a key role in cystic fibrosis, Elkins says. Cystic fibrosis, which afflicts about 30,000 Americans, is caused by a defect in a gene that controls the amount of salt and water that line the airways of the lungs. Without sufficient lubrication, mucus builds up and blocks the airways, providing a fertile home for bacteria.

Doctors in Australia and the USA decided to test whether saltwater might replace that missing lubrication. They hoped the extra salt would draw water out of lung tissue onto the airway, providing a thin layer of liquid to ease mucus out of the lung, says Richard Boucher, who directs the cystic fibrosis center at the University of North Carolina-Chapel Hill and led the American study.

Researchers found that inhaling an intensely salty solution — almost twice as salty as the Atlantic Ocean — improved patients' lung function and slowed the progression of the disease, according to articles published in Thursday's New England Journal of Medicine. Australian doctors found that 41% of those who received the treatment avoided serious complications — such as weight loss, coughing up blood or a dangerous infection — compared with 16% of the other patients. The solutions helped remove mucus from the lung for at least eight hours, according to the UNC study of 24 patients, also published in the journal.

Doctors probably will begin using the treatments right away, says Peter Mogayzel, director of the Johns Hopkins Cystic Fibrosis Center, who was not involved in the study. His center began offering the treatment last year after seeing preliminary results at a conference.

The treatments don't cure cystic fibrosis and won't replace current therapies, Elkins says. Some patients already spend hours a day treating their disease, so adding another 30-minute therapy could be a burden. To make the treatments easier to use, researchers are testing a device that works four times more quickly than current systems.

Felix Ratjen of the University of Toronto, who wrote an editorial accompanying the studies, notes that the saltwater treatment may have a limited benefit, because it may not reach the most clogged airways. But Boucher hopes the treatments could prevent damage, especially in babies whose lungs are still unscarred. He plans to begin tests soon in infants as young as 2 months.

The new therapy is also relatively cheap. The Cystic Fibrosis Foundation estimates the cost to be about $110 a month, less than one-tenth the cost of other drugs. Scott Donaldson, an assistant professor at UNC and co-author of that study, says, "Something simple has turned out to be very good."

Source: http://www.usatoday.com/news/health/2006-01-18-cystic-fibrosis_x.htm

January 12, 2006
Press release
Vertex Pharmaceuticals and Cystic Fibrosis Foundation Therapeutics Extend Collaboration for Cystic Fibrosis Drug Research

CAMBRIDGE, Mass. and BETHESDA, Md., Jan. 12 /CNW/ -- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX - News) and Cystic Fibrosis Foundation Therapeutics, Inc. (CFFT) today announced that they have extended their research collaboration. Under the extended agreement, CFFT will provide an additional $22 million to Vertex for continued research funding through early 2008 to further develop Vertex's proprietary "corrector" compounds that act to restore the function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, the defective cell membrane protein responsible for the progression of cystic fibrosis (CF). CFFT is the nonprofit drug discovery and development affiliate of the Cystic Fibrosis Foundation.

"The expansion of this collaboration with Vertex underscores our belief that the development of small molecule agents to address the underlying defect of cystic fibrosis is our highest priority and has the greatest potential to fundamentally change the treatment of the disease," said Robert J. Beall, Ph.D., President and CEO of the CF Foundation and CFFT. "CFFT and Vertex share a long-standing and fruitful collaborative history in CF research. Together, we look forward to the discovery and development of novel treatments that may provide new therapeutic options for thousands of CF patients."

"Vertex's cystic fibrosis research program has yielded two innovative approaches for the treatment of this disease," said Joshua Boger, Ph.D., Chairman, President and CEO of Vertex. "This research extension of the CFFT collaboration underscores our commitment to developing new treatments for this major unmet medical need and supports Vertex's continued investment focus in this key therapeutic area."

CF Drug Discovery

Using proprietary expertise in ion channels, including high-content cell assays and medicinal chemistry, Vertex has identified selective ion channel modulators for the treatment of CF. With the support of CFFT, Vertex's CF research has focused on two possible alternative approaches to CF treatment, known as "potentiator" and "corrector" approaches. Each approach might address a different molecular defect in the CFTR protein that is responsible for CF. Defects in the CFTR protein affect the transport of chloride and other ions across cells, and lead to the accumulation of thick, sticky mucus in the lungs. This mucus fosters chronic infection and inflammation and ultimately results in irreversible lung damage.

Potentiator compounds may work by increasing the probability that the CFTR channel is open, which could result in an increase in chloride transport across the cell surface. Corrector compounds may work by increasing the number of CFTR channels on the cell surface. At the 16th Annual Williamsburg Conference in June 2004, Vertex researchers demonstrated the potential of both corrector and potentiator compounds to improve CFTR function in vitro in bronchial epithelial cells isolated from CF patients.

CFFT Collaboration

Vertex initiated its CF research program in May 2000 as part of a collaboration with CFFT, and expanded the agreement in May 2004. Under the extended agreement announced today, CFFT will provide to Vertex approximately $22 million in additional contracted payments for corrector research through the first quarter of 2008, with the first payment to be received in the first quarter of 2006. Vertex retains the right to develop and commercialize any compounds discovered under the agreement, and will pay CFFT royalties on net sales.

About Cystic Fibrosis and the Cystic Fibrosis Foundation

The Cystic Fibrosis Foundation, headquartered in Bethesda, MD, is a donor- supported, nonprofit organization committed to finding therapies and ultimately a cure for CF, and to improving the lives of those with the disease. For more information on CF and the programs of the CF Foundation, call (800) FIGHT CF or visit http://www.cff.org.

About Vertex

Vertex Pharmaceuticals Incorporated is a global biotechnology company committed to the discovery and development of breakthrough small molecule drugs for serious diseases. The Company's strategy is to commercialize its products both independently and in collaboration with major pharmaceutical companies. Vertex's product pipeline is principally focused on viral diseases, inflammation, autoimmune diseases and cancer. Vertex co-promotes the HIV protease inhibitor, Lexiva, with GlaxoSmithKline.

Lexiva is a registered trademark of the GlaxoSmithKline group of companies.

Vertex Safe Harbor Statement

This press release may contain forward-looking statements, including statements that (i) CFFT will provide an additional $22 million to Vertex for continued research funding through early 2008; (ii) small molecule agents have the potential to fundamentally change the treatment of the disease; and (iii) novel CF treatments discovered under this collaboration may provide new therapeutic options for CF patients. While management makes its best efforts to be accurate in making forward-looking statements, such statements are subject to risks and uncertainties that could cause Vertex's actual results to vary materially. These risks and uncertainties include, among other things, the possibility the CFFT could terminate its financial support under the agreement without cause, risks that efforts to select and optimize development candidates may not proceed due to financial, technical, commercial or other reasons, that laboratory results may not be predictive of future clinical results for any compounds selected for human clinical study and other risks listed under Risk Factors in Vertex's Form 10-K filed with the Securities and Exchange Commission on March 16, 2005.

Source: Vertex Pharmaceuticals

January 11, 2006
Inhaled drug boosts lung transplant survival

By Gene Emery

BOSTON (Reuters) - Lung transplant patients live longer when they inhale the rejection-fighting drug cyclosporine, a study showed on Wednesday.

About 1,700 lung transplants are done at 150 centers around the world each year. But they are among the riskiest types of transplant surgery. Nearly half of recipients die within three years, and the long-term survival rate has changed little since the 1980s.

In the new University of Pittsburgh Medical Center study, led by Aldo Iacono, now at the University of Maryland in Baltimore, the death rate among the 28 patients selected to receive inhaled cyclosporine was 11 percent, far below the rate of 47 percent among the 30 volunteers who inhaled a placebo. "We were surprised to see this kind of survival," Iacono told Reuters.
Also, the likelihood of long-term rejection was also lower, and "there is no therapy which is shown to prevent chronic rejection. This is the first one," he said. "These results should be received enthusiastically by lung-transplant physicians and surgeons but need to be confirmed," said Malcolm DeCamp in an editorial in The New England Journal of Medicine, where the study appears.But it's not clear how the findings will be confirmed. No further tests of the inhaled Chiron Corp. form of cyclosporine, known as Pulminiq, are planned by the company, a spokesman said.

Last summer, a U.S. Food and Drug Administration advisory panel looked at these results and split 8-8 over whether the findings showed that the drug is effective as a lung transplant treatment. The panel suggested more tests. But Iacono said the only Pulminiq study under way is designed to test the effectiveness of the drug after other treatments have failed. No new patients are being enrolled in that test. The inability to give the drug to new transplant recipients, even on an experimental basis, is "a major issue," he told Reuters. The new study had its shortcomings, said DeCamp.

The number of patients who signed up was less than half of what the investigators wanted, only half the volunteers were able to stay with the two-year treatment, and the drug didn't seem to cut down on the instances of short-term rejection, a typical measure of success.

Although lung transplants have been around for decades, the Iacono study was the first to use a placebo and double-blind conditions to assess post-operative treatment. DeCamp, of Beth Israel Deaconess Medical Center in Boston, said medical centers need to cooperate better to find the optimal treatment for newly transplanted lungs. "Without a mechanism for sharing experiences, studying new therapies and techniques, and critically analyzing pooled outcomes, the lung-transplantation community will never establish a set of best practices," he said. "Perhaps the inhaled-cyclosporine story will be that breath of fresh air that brings this community together."

January 5, 2006
Press Release
Aradigm Files Request for Orphan Drug Designation for Inhaled Liposomal Ciprofloxacin for Cystic Fibrosis

HAYWARD, CA--(MARKET WIRE)--Jan 5, 2006 -- Aradigm Corporation (NasdaqNM:ARDMD - News) today announced that it has filed a request for orphan drug designation with the United States Food and Drug Administration (FDA) for its liposomal ciprofloxacin product for the management of cystic fibrosis (CF).

Orphan drug status may be granted to drugs that treat rare life-threatening diseases that affect less than 200,000 persons in the United States. Such designation provides a company with seven years of marketing exclusivity for a selected drug approved by the FDA along with regulatory assistance, reduced filing fees and possible tax credits.

The clinical program will investigate the pulmonary delivery of the novel formulation of this widely used anti-infective for its local and prolonged effects in the treatment of bacterial infections in CF. Aradigm's liposomal formulation is designed to change the short-acting nature of ciprofloxacin so that it becomes long-acting and remains in the lung for a sufficient amount of time to treat pseudomonas infections commonly found in patients with CF.

Aradigm recently hosted a meeting of leading CF medical experts to discuss the use of liposomal ciprofloxacin in this patient population. These thought leaders expressed an opinion that this innovative therapeutic product could meet an important unmet medical need as an additional antibiotic to treat respiratory infections in CF.

"We believe that liposomal ciprofloxacin could play an important role in improving the quality of life of patients with cystic fibrosis," said Babatunde Otulana, M.D., Vice President of Clinical and Regulatory Affairs at Aradigm. "Aradigm will advance this program through development and utilize the financial and regulatory benefits that orphan drug status provides."

CF is a genetic disease affecting roughly 30,000 children and adults in the United States and roughly 60,000 worldwide. This defective gene causes production of excess mucus that clogs the lungs and often leaves patients vulnerable to life threatening lung infections. CF is the most common fatal genetic disease in the United States.

Aradigm combines its non-invasive delivery systems with novel formulations to create products that enable patients to comfortably self-administer biopharmaceuticals and small molecule drugs. The company's advanced AERx® pulmonary and Intraject® needle-free delivery technologies offer rapid delivery solutions for liquid drug formulations. Current development programs and priorities focus on the development of specific products, including partnered and self-initiated programs in the areas of respiratory conditions, neurological disorders, heart disorders, smoking cessation, and diabetes. More information about Aradigm can be found at www.aradigm.com.

Except for the historical information contained herein, this news release contains forward-looking statements that involve risk and uncertainties, including clinical results, the timely availability and acceptance of new products, the impact of competitive products and pricing, the availability of funding from partners or capital markets, and the management of growth, as well as the other risks detailed from time to time in Aradigm Corporation's Securities and Exchange Commission (SEC) Filings, including the company's Annual Report on Form 10-K, and quarterly reports on Form 10-Q.

Aradigm, AERx and Intraject are registered trademarks of Aradigm

Source: Aradigm Corporation

January 1, 2006
Public release
Cystic fibrosis clinical study patients show less lung function decline

Although cystic fibrosis patients in clinical trials had more severe illness, worse lung function, a lower weight level and more respiratory infection than non-participants, their involvement in research studies resulted in less lung function decline over a 7-year period.

The research results appeared in the first issue for January 2006 of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.

Christopher H. Goss, M.D., M.Sc., of the Departments of Medicine and Pediatrics at the University of Washington Medical Center in Seattle, along with three associates, looked at data from 13,041 patients in the Cystic Fibrosis Foundation Registry between 1992 and 1998.

Despite their worse clinical status at the beginning of the study, participants' lung function declined at 1.33 percent per year, as compared with 1.52 percent for non-participants.

Of the 8,375 patients followed for the entire 7-year study period, 2,635 individuals (30.2 percent) were enrolled in at least 1 of 32 Institutional Review Board clinical trials.

"Subjects who were involved in clinical trials were more likely to be older, have commercial health insurance, be white, be colonized with a bacterial infection like Pseudomonas aeruginosa, have worse lung function and have more office visits," said Dr. Goss.

Cystic fibrosis (CF), one of the most common inherited life-shortening illnesses, is characterized by the production of thick, sticky mucus that eventually blocks the small airways, leading to inflammation and infection. Mucus also affects the pancreatic ducts, preventing normal digestion and weight gain. Respiratory failure is the primary cause of early death. CF incidence runs from 1 in 2,000 to 1 in 3,200 live births.

According to the authors, access to better health care through more office visits appeared to be the reason explaining less lung function decline for clinical trial participants.

"Given that there may be potential benefits to study participation, CF clinicians need to ensure adequate opportunities for participation in studies for all eligible subjects," said Dr. Goss.

He added that the persons most likely to participate in the study were those without a high school education who worked full-time.

According to the authors, this CF study was the first to compare clinical trial participants against a majority in a disease category within a specific country.

Source: American Thoracic Society

December 20, 2005
Behavioral and nutritional counseling improves energy intake and promotes normal growth in toddlers and preschoolers with cystic fibrosis (CF)

NEW YORK (Reuters Health) - Behavioral and nutritional counseling improves energy intake and promotes normal growth in toddlers and preschoolers with cystic fibrosis (CF), according to results of a small study. Toddlers and preschoolers with CF often fall short of nutritional recommendations for this disease, which leads to impaired growth. This is a major problem because adequate growth from 3 to 6 years of age is associated with better lung function later on.

In the study, four young children with CF and their families were randomly assigned to 8 weeks of behavioral and nutrition intervention (BEH) and six age-matched children with CF and their families were assigned to usual care consistent with CF Foundation guidelines on nutritional care.

The intervention included nutrition counseling to increase energy intake and child behavioral management training.

The dietary intake intervention group met the clinical benchmarks of 120 percent to 150 percent RDA for energy and 35 percent to 40 percent fat intake suggested by the 2 consensus conferences on pediatric nutrition in CF, the investigators report.

Children in the control arm, in contrast, failed to show any change in energy or fat intake over the 8-week study period, despite guideline-driven nutritional care.

However, five of the six control children and their families who chose to receive the BEH intervention after the study saw significant increases in energy and fat intake as a result.

The impact of the 8-week counseling program seems to be durable, Dr. Scott W. Powers from Cincinnati Children's Hospital and colleagues report in the journal Pediatrics, noting that children who received it maintained the clinically significant increase in energy and fat intake at 3 and 12 months after treatment.

This, they say, suggests that families are able to continue to implement the skills and knowledge provided during counseling without ongoing contact with the research team or additional booster treatment sessions.

Summing up, Powers told Reuters Health, "it also appears that the intervention has great potential for improving growth." In fact, he added, a large controlled clinical trial evaluating the impact of behavioral and nutrition treatment on growth is planned.

SOURCE: Pediatrics December 2005

December 16, 2005
Press Release
Bronchitol(TM) European Cystic Fibrosis Study Commences

SYDNEY, Australia, Dec. 16 /Xinhua-PRNewswire-FirstCall/ -- Pharmaxis Ltd (ASX: PXS - News; Nasdaq: PXSL - News) announced today that a Phase II clinical trial in patients with cystic fibrosis has commenced its dosing phase. The study, which aims to determine the benefits of Bronchitol in children also receiving the market leading treatment, rhDNase, is being conducted at 2 sites in the United Kingdom.

Pharmaxis Chief Executive Officer Alan Robertson said: ''Our previous clinical study demonstrated that Bronchitol offers significant benefit for people with cystic fibrosis. This trial will enable us to understand how Bronchitol performs in conjunction with the leading treatment for mucus clearance and help position Bronchitol in the marketplace. It's an important study that will run in parallel with our final Phase III program.''

Patients enrolled in the study will receive three months treatment with each of three different therapies -- Bronchitol alone, both Bronchitol and rhDNase together and rhDNase alone. The trial will measure changes in lung function, airway inflammation, infections, and quality of life. Full patient recruitment is expected to take about eight months.

Approximately 75,000 people in the major pharmaceutical markets are affected with cystic fibrosis and no products have been approved to improve lung hydration.

Pharmaxis (ACN 082 811 630) is a specialist pharmaceutical company involved in the research, development and commercialization of therapeutic products for chronic respiratory and autoimmune diseases. Its development pipeline of products includes Aridol for the management of asthma, Bronchitol for cystic fibrosis and chronic obstructive pulmonary disease (COPD) and PXS25 for the treatment of multiple sclerosis.

Founded in 1998, Pharmaxis was listed on the Australian Stock Exchange in November 2003 (symbol PXS), and on NASDAQ (symbol PXSL) in August 2005. The company is headquartered in Sydney at its TGA-approved manufacturing facilities.

For more information about Pharmaxis, go to www.pharmaxis.com.au or contact Jane Sugden, Investor Relations +61 2 9451 7230.

About Bronchitol

Pharmaxis Ltd is developing Bronchitol for the management of chronic obstructive lung diseases including cystic fibrosis, bronchiectasis and chronic bronchitis.

Bronchitol is a proprietary formulation of mannitol administered as a dry powder in a convenient hand-held inhaler. It is designed to hydrate the lungs, restore normal lung clearance mechanisms, and help patients clear mucus more effectively.

Clinical studies have shown Bronchitol to be well tolerated, to improve quality of life, and to stimulate mucus hydration and clearance in people with cystic fibrosis and bronchiectasis.

Longer term clinical studies involving Bronchitol in cystic fibrosis and bronchiectasis are underway. These studies aim to demonstrate an improvement in lung function and quality of life, and a reduction in infection and physiotherapy needs.

About cystic fibrosis

Cystic Fibrosis (CF) is a hereditary, life-limiting disease that affects the body's exocrine glands which produce mucus, saliva, sweat and tears. In this disease, a genetic mutation disrupts the delicate balance of sodium, chloride and water within cells, causing the exocrine glands to secrete fluids that are thick, sticky and poorly hydrated. This leads to chronic problems in various body systems, especially the lungs and pancreas, and the digestive and reproductive systems.

The thick mucus in the lungs severely affects the natural airway-clearing processes and increases the potential for bacteria to become trapped, resulting in respiratory infections that may require hospitalisation. Impairments to these essential lung defence mechanisms typically begin in early childhood and often result in chronic secondary infections, leading to progressive lung dysfunction and deterioration.

In Australia, 2,500 people are living with CF, about one fifth of whom are children under five years of age. In the U.S., over 30,000 people are affected.

Pharmaxis is dedicated to developing products to treat this debilitating disease.

Forward-Looking Statements

The statements contained in this press release that are not purely historical are forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements in this press release include statements regarding our expectations, beliefs, hopes, goals, intentions, initiatives or strategies, including statements regarding the safety and effectiveness of Bronchitol in treating cystic fibrosis or the timing or ability of the Company to obtain regulatory approval of Bronchitol or to obtain orphan drug exclusivity in the U.S. All forward- looking statements included in this press release are based upon information available to us as of the date hereof, and we assume no obligation to update any such forward-looking statement as a result of new information, future events or otherwise. We can not guarantee that any product candidate will receive FDA or other regulatory approval or that we will seek any such approval. Factors that could cause or contribute to such differences include, but are not limited to, factors and risks disclosed from time to time in reports filed with the Securities and Exchange Commission, including our Registration Statement on Form F-1.

Source: Pharmaxis Ltd

December 13, 2005
Fatty Acids May Help Treat Chronic Lung Disease

NEW YORK (Reuters Health) - Healthy fats found in fish and vegetable oils may help ease the inflammation that marks chronic lung disease, preliminary research suggests.

In a small study of adults with chronic obstructive pulmonary disease (COPD), Japanese researchers found that supplements of omega-3 fatty acids appeared to improve patients' breathing difficulties -- possibly by countering the airway inflammation seen in the disease.

Dr. Wataru Matsuyama and colleagues at Kagoshima University Hospital report the findings in the medical journal Chest.

Omega-3 polyunsaturated fatty acids, or PUFAs, are found largely in oily fish, and to a lesser extent in flaxseed, walnuts, soybeans and canola oil. Research has suggested that these fats -- particularly fish oils -- may help lower the risk of heart disease and other ills, possibly due to their anti-inflammatory effects.

COPD is a group of serious lung diseases that includes emphysema and chronic bronchitis. Since airway inflammation is a major feature of these illnesses, Matsuyama's team theorized that omega-3 supplements might improve patients' symptoms.

To investigate, they randomly assigned half of the 64 patients to drink a liquid supplement rich in omega-3 fats each day; the other half drank a supplement containing omega-6 fats, another type of polyunsaturated fat found in many foods, including vegetable oils and meat.

After two years, patients in the omega-3 supplement group showed an overall improvement on tests that measured their breathing during a short bout of exercise. At the same time, levels of certain inflammatory proteins in their blood and mucus generally declined -- suggesting that the improvements in lung capacity arose from the anti-inflammatory effects of the fatty acids.

Though larger, longer studies are needed to confirm the results, the researchers note that the findings are in line with American Heart Association recommendations to eat a diet rich in omega-3 fats for heart health.

"Taken together, we recommend nutritional support with omega-3 PUFAs for the nutritional treatment of COPD," they conclude.

However, it's important that people with COPD have a generally healthy diet as well, according to Matsuyama. Significant weight loss is a common complication of COPD and patients need not only omega-3 fatty acids, but an adequate diet overall to prevent this, Matsuyama told Reuters Health. That's why study patients were given a high-calorie liquid supplement rather than a pill.

The researchers plan to do another study of a larger group of patients to see how omega-3 fats affect their long-term prognosis.

SOURCE: Chest, December 2005

November 15, 2005
The European Medicines Agency has granted orphan drug designation to Pharmaxis' investigational drug Bronchitol for the treatment of cystic fibrosis

Orphan designation has been granted on the basis of Bronchitol's potential to treat cystic fibrosis, a genetic disease which, for the patient, is characterized by recurring respiratory complications. Approximately 75,000 people in the major pharmaceutical markets are affected with cystic fibrosis and no products have been approved to improve lung hydration.

"This European Orphan designation is another major step forward in the development of Bronchitol," commented Alan Robertson, Pharmaxis CEO. "The assistance from the EMEA in the final development of Bronchitol will be invaluable in bringing this product to the cystic fibrosis community."

A recent phase II trial of the drug in cystic fibrosis patients demonstrated statistically significant improvements in lung function for patients being treated with Bronchitol. Pharmaxis is conducting an additional phase II trial aimed at determining the optimal Bronchitol dose for cystic fibrosis and is planning to commence the final international phase III clinical trials in 2006.

Source: Datamonitor Newswire

November 14, 2005
Press Release
PARI Issued US Patent for eFlow; Device Innovations Lead to Greater Efficiency in Drug Delivery

MONTEREY, Calif., Nov. 14 /PRNewswire/ -- PARI has been granted US Patent 6,962,151 relating to technological advances in the eFlow electronic nebulizer that result in significant improvements in aerosol medication delivery. This technology aerosolizes medication more efficiently, so patients experience dramatically shorter treatment times while receiving complete therapies. This has the potential to improve therapies for diseases such as asthma, cystic fibrosis, and COPD.

The new "mixing chamber" patent covers an aerosol chamber, inhalation and exhalation valves, a liquid storage container, and an aerosol generator based on a vibrating membrane technology. These components improve delivery of medication by two- to three-fold compared to other available nebulizers. Other nebulizers operating with a continuous output mode tend to waste up to half of the aerosolized medication when patients exhale during treatment. PARI's eFlow suspends an aerosol cloud in a "mixing chamber" until the patient inhales in their normal, spontaneous manner, thereby reducing the amount of medication needed to deliver a therapeutically effective dose.

"While there are currently two other vibrating mesh nebulizers on the market (the Omron MicroAir and the Aeroneb Go), only eFlow has the aerosol chamber. PARI will retain exclusivity on this feature for 20 years from the priority issuance date of 1999," summarizes Dr. Roland Stangl, responsible for Technology Development and device IP at the PARI Aerosol Research Institute, Germany.

"This patent is a significant milestone for the eFlow product platform because eFlow's unique technology allows it to achieve a 65% - 75% delivered dose when other nebulizers may, at best, achieve a 30% - 40% delivered dose," said Geoff A. Hunziker, Senior Vice-President for the PARI Aerosol Research Institute, USA. The delivered dose is the inhaled mass or amount of aerosolized drug that comes out of the nebulizer and is inhaled by the patient.

In May 2005, Dr. David Geller, a leading Pediatric Pulmonologist at Nemours Children's Hospital in Orlando, Florida, published the findings mentioned by Mr. Hunziker and presented the study at the American Thoracic Society Meeting in San Diego.

"In addition to eFlow's efficiency, it was also designed as a customizable platform for new drug formulations. This allows the drug to be optimized to the device and the device to be optimized to the drug on a variety of features, including droplet size, speed of delivery, volume of the medication reservoir, size and design of the aerosol chamber depending on the mode of administration, and the patient interface," stated Dr. Martin Knoch, Managing Director of PARI GmbH. "With these advancements, we have the potential to significantly improve patient compliance and change the paradigm in how aerosol treatments are taken in the future. This is the improvement in quality of life that patients and physicians are always looking for."

PARI has also been granted Patents 5152456, 5261601, and 5518179 with several others pending related to eFlow and its technologies. Over 80 studies have been presented or published on the eFlow and advanced aerosol delivery solutions.

About eFlow

eFlow, an electronic, portable nebulizer, enables extremely efficient aerosolization of liquid medications via a vibrating, perforated membrane. Compared to other nebulizer systems, eFlow can produce aerosols with a very high density of active drug, a precisely defined droplet size, and a high proportion of respirable droplets delivered in the shortest possible amount of time. Combined with its silent mode of operation, small size (it fits in the palm of your hand), light weight, and battery use, eFlow helps reduce the burden of taking daily inhaled treatments.

About PARI

PARI is a leading worldwide developer and manufacturer of fast and efficient aerosol delivery systems for patients with asthma, chronic lung disease, and cystic fibrosis. PARI's primary focus is to provide patients with innovative products and services that help control disease. PARI is headquartered in Starnberg, Germany with a major presence in the United States and offices in Japan, United Kingdom, and China.

Source: PARI

November 13, 2005
Genes involved in biofilms of Staphylococcus aureus

The biologist Alejandro Toledo Arana has identified two new genes that operate as regulators in the formation process of the biofilm of Staphylococcus aureus, one of the bacteria most frequently involved in infections following medical implants, and has explained the functioning of a structural protein involved in this process. His research was the subject of a PhD thesis recently defended at the Institute of Agribiotechnology, a joint CSIC and Public University of Navarra centre, and is an advance in the race to identify action targets for the development of pharmaceutical drugs to combat these infections.

The PhD, entitled Identification and characterisation of new factors involved in the processes of formation of biofilm from Gram-positive bacteria.

Chronic infections

Biofilms are communities of microorganisms in a matrix that joins them together and to living or inert substrates, points out Alejandro Toledo. Although they are widely found in nature, and in many cases have beneficial effects, their study has been boosted on discovering their relation to chronic infections associated to medical implants such as those tissues involving infections of the middle ear, of the prostate gland, pneumonia in patients with cystic fibrosis, osteomyelitis, etc.

In the interior of the biofilm, bacteria present greater resistance to antibiotics, to the opsonisation by antibodies and to phagocytosis, which explains the chronic character of these infections, states the author of the PhD.

The aim of the PhD was the characterisation of the process of formation of the Staphylococcus aureus biofilm.

Regulating mechanisms unknown to date

The starting point for the research was the Bap protein (Biofilm associated protein). Bap, according to the thesis, presents a structural organisation similar to other surface proteins of unknown function in a number of species of bacteria such as: Esp de Enterococcus faecalis, mus20 of Pseudomonas putida, and sty2875 of Salmonella typhi.

Thus, taking into account the structural homology between Bap and Esp, it was decided to analyse for a possiblerelationship between the presence of the esp gene and the ability to produce biofilm by E. faecalis. The results showed that the presence of the esp gene was involved in the formation processes of these biofilms.

Two new genes

The results obtained to date intuitively suggest the existence of various mechanisms for forming biofilm as a function of the origin of the bacteria strains, as a consequence of which it was decided to widen the scope of the research, using a strain of Staphylococcus aureus from otitis media.

For the identification of the genes involved in the formation of the biofilm of this strain, two different strategies were followed. The first, following the usual methods, involved identifying mutants that had lost the capacity to form biofilm, thus enabling identification of the essential genes and positive regulators of the process. The results showed that a positive regulator known as Pnp (Polynucleotide phosphorylase) exists and which regulates the accumulation of the main exopolysaccharide involved in the formation of the biofilm for this bacteria.

Moreover, the second strategy arose during the development of a medium chemically defined in order to study how environmental signals affect the process of formation of the biofilm. Unexpectedly, most of the clinical strains of Staphylococcus aureus were unable to form biofilm in the synthetic medium, which suggested to us that the process was, perhaps, repressed in this medium.

Source: Garazi Andonegi, Elhuyar Fundazioa

October 17, 2005
Breath test offers hope for early detection of lung-bacteria growth in cystic fibrosis

Cystic fibrosis patients found to have elevated sulfur content in exhaled breath

Irvine, Calif. -- Breath-analysis testing may prove to be an effective, non-invasive method for detecting the damaging lung-bacteria growth seen in cystic fibrosis, which would allow for early stage treatments that can extend the health of people with this disease, UC Irvine researchers have found.

By using a chemical analysis method developed for air-pollution testing, UCI chemists and pediatricians have found that people with cystic fibrosis exhale higher concentrations of sulfur compounds from their lungs than do people who don't have the disease.

These sulfur compounds, called sulfides, are known to be produced by bacteria, and lung disease in cystic fibrosis is accompanied by bacterial infections that cause chronic damage. The researchers found that the worse the pulmonary function in the cystic fibrosis patient, the higher the sulfide concentration in the breath sample, suggesting an increased amount of bacterial growth in the lungs.

"Early detection and antibiotic therapy has been promoted as a means to delay chronic bacterial lung growth and prolong life, and breath analysis may be an effective first step toward treatment," said Dr. Dan Cooper, a pediatric pulmonologist at UCI Medical Center, who led the study with F. Sherwood Rowland, the Donald Bren Research Professor of Chemistry, and fellow chemistry professor Donald Blake. "In the long term, these findings on sulfide levels also might help uncover some of the underlying mechanisms of the disease."

Study results appear this week in the early online version of the Proceedings of the National Academy of Sciences.

Cystic fibrosis is a genetic disease marked by an abnormally thick, sticky mucus that clogs the lungs and leads to life-threatening lung infections. Although many lung bacteria are prevalent with the disease, in teens and adults, the Pseudomonas aeruginosa bacteria appears as the most prevalent cystic fibrosis pathogen and is strongly associated with respiratory deterioration and mortality. Over time, the bacteria transforms into treatment-resistant variants, and early detection is seen as key for aggressive antibiotic treatments to delay its growth.

In the study, graduate student Michael Kambourse, working with Blake and Rowland, examined exhaled breath from people with and without cystic fibrosis using laboratory methods developed for their atmospheric chemistry work. In that work, they measure the levels of trace gases in excess of the parts-per-billion range that contribute to local and regional air pollution. Their research group is one of the few in the world recognized for its ability to measure accurately at such small amounts.

In analyzing the breath samples, the researchers monitored levels of three sulfides in the cystic fibrosis patients -- carbonyl sulfide, dimethylsulfide and carbon disulfide. Significantly, they found that cystic fibrosis patients exhaled carbonyl sulfide (OCS) at rates up to 2½ times higher than people who don't have the disease, making it an attractive target for future breath analysis.

The study determined that the regular air the test subjects breathed in had about 600 parts-per-trillion volume (pptv) of OCS. The non-cystic fibrosis subjects exhaled a mean average of 350 pptv of OCS, meaning that about 250 pptv of OCS was removed from the inhaled air. The cystic fibrosis subjects exhaled a mean average 490 pptv of OCS, and the three individuals with the weakest pulmonary function exhaled as much as 800 pptv, producing an excess of OCS. This suggests a substantial OCS source, probably bacterial, exists in their lungs, in addition to poorer processing of inhaled gas.

The researchers are continuing their breath-analysis work in areas of autism, diabetes and oral glucose tolerance testing. Most relevant are ongoing studies in which they are testing the profile of gases produced by bacteria, like P. aeruginosa.

"The ultra-trace gas breath analysis techniques used in this study not only show potential for cystic fibrosis treatment but possess wide-ranging clinical possibilities," Blake said.

The National Institutes of Health, the Cystic Fibrosis Foundation and the Joan Irvine Smith and Athalie R. Clarke Foundation supported the study.

About Cystic Fibrosis:

Cystic fibrosis is a genetic disease affecting approximately 30,000 children and adults in the United States. A defective gene causes the body to produce an abnormally thick, sticky mucus that clogs the lungs and leads to life-threatening lung infections. These thick secretions also obstruct the pancreas, preventing digestive enzymes from reaching the intestines to help break down and absorb food. The mucus also can block the bile duct in the liver, eventually causing permanent liver damage in approximately six percent of people with the disease. Because of improvements in antibiotics, exercise and diet, people with cystic fibrosis on average live into their 30s. (Source: Cystic Fibrosis Foundation)

About the University of California, Irvine: Celebrating 40 years of innovation, the University of California, Irvine is a top-ranked university dedicated to research, scholarship and community service. Founded in 1965, UCI is among the fastest-growing University of California campuses, with more than 24,000 undergraduate and graduate students and about 1,400 faculty members. The second-largest employer in dynamic Orange County, UCI contributes an annual economic impact of $3 billion. For more UCI news, visit www.today.uci.edu.

Television: UCI has a broadcast studio available for live or taped interviews. For more information, visit http://today.uci.edu/broadcast.

News Radio: UCI maintains on campus an ISDN for conducting interviews with its faculty and experts. The use of this line is available free-of-charge to radio news programs/stations who wish to interview UCI faculty and experts. Use of ISDN line limited by availability and approval by the university.

UCI maintains an online directory of faculty available as experts to the media. To access, visit www.today.uci.edu/experts.

Source University of California - Irvine

October 3, 2005
Special Issue on Cystic Fibrosis in the Journal of Pediatrics

Description

The Journal of Pediatrics has published a special supplement on current experience in treating cystic fibrosis and the benefit of newborn screening for cystic fibrosis. The supplement consists of 23 commentaries, reviews, and original research papers.

Newswise — Cystic fibrosis is a common, fatal genetic disease in which a gene causes the body to produce abnormally thick, sticky mucus. This affects mainly the lungs, causing severe breathing problems, and the digestive system, causing inadequate digestion and absorption of nutrients. In the United States, approximately 30,000 people have cystic fibrosis and roughly one child of every 3,500 is born with it. The Journal of Pediatrics has published a special supplement on current experience in treating cystic fibrosis and the benefit of newborn screening for cystic fibrosis. The supplement consists of 23 commentaries, reviews, and original research papers derived from a workshop held in Atlanta, Georgia, November 20-21, 2003, co-sponsored by the Centers for Disease Control and Prevention and the Cystic Fibrosis Foundation. In addition, the regular issue of The Journal includes 11 articles on cystic fibrosis that cover such topics as a reduction in birth rates since the onset of genetic testing, decreased birth weights and increased risk of preterm birth, an alternative strategy for screening newborns at reduced cost, and projects intended to improve life expectancy and quality of life through consistent, high-quality care.

Reduction in birth rates

A paper from Canada comments on a reduction in cystic fibrosis birth rates that has been observed since the onset of genetic testing. The paper, from Anne Dupuis and colleagues at the Hospital for Sick Children, Toronto, and Dalhousie University, Nova Scotia, shows that the overall cystic fibrosis birth rate was stable from 1971-1987 and, beginning in 1988, one year after identification of the cystic fibrosis transmembrane conductance regulator gene, birth rates started a linear decline to an estimated rate of 1 in 3,608. Cystic fibrosis birth rates appear to have stabilized in the last few years, but the authors speculate that further decline may occur with implementation of carrier screening in the general population. The title of the article is “Cystic fibrosis birth rates in Canada: A decreasing trend since the onset of genetic testing.”

Gestational and neonatal characteristics

A group of authors led by Filippo Festini report the gestational and neonatal characteristics of children with cystic fibrosis. This was a retrospective cohort study of all children with cystic fibrosis born in Tuscany, Italy, from 1991 to 2002 that compared them to the entire population of non-affected children born in the same period. There were 70 children with cystic fibrosis and 290,059 non-affected children. The mean birth weight of the newborns with cystic fibrosis was 246g lower than the mean birth weight of the non-affected population. The children with cystic fibrosis also had a higher risk of being preterm with a relative risk of 2.62 associated with a lower birth weight and an increased risk of being small for gestational age. The reduced birth weight was present even in the absence of prematurity and the full-term newborns with cystic fibrosis were lighter than the full term non-affected babies. The reduced birth weight in newborns with cystic fibrosis has been reported before, but the greater risk of being preterm is a new observation. The title of the article is “Gestational and neonatal characteristics of children with cystic fibrosis: A cohort study.”

Screening newborns

An alternative strategy for screening newborns for cystic fibrosis has been studied in France. Sarles and colleagues from several centers report on the strategy of combining pancreatitis-associated protein (PAP) with immunoreactive trypsinogen (IRT) assays on newborn blood screening cards. The screening strategy was testing in all newborns from 5 French regions with 204,749 births. Results showed that combining the results of IRT with PAP and recalling patients for sweat testing when the IRT was greater than 100 ng/mL and PAP greater than 1.0 ng/mL would have a similar performance to the IRT/CFTR mutation strategy with reduced cost and without the genetic issue of identification of carrier through mutation analysis. The title of the article is “Combining immunoreactive trypsinogen and pancreatitis-association protein assays, a method of newborn screening for cystic fibrosis that avoids DNA analysis.”

Improving outcomes

In North America, considerable effort is going into improving outcomes in cystic fibrosis by improving the consistency and quality of care. It has been estimated that more than a 10-year increase in average life expectancy could be achieved using current approaches if they were applied consistently according to best practice. A leader in this effort, Michael Schechter from Brown University, was invited to write a commentary in which he describes developing optimal approaches to care and uses cystic fibrosis as an example of what can be achieved. Schechter presents several quality improvements that are in progress in cystic fibrosis such as the “Learning and Leadership” collaborative funded by the Cystic Fibrosis Foundation. Schechter’s article is the subject of an accompanying editorial by James Acton; he reinforces the concept that unwarranted variation in care leads to adverse outcomes in healthcare and that it is possible to improve results through system-based changes that support evidence-based, patient-centered care. The title of the article is “Improving subspecialty healthcare: Lessons from cystic fibrosis.” The title of the editorial is “Improvements in healthcare: How can we change the outcome?”

The Journal of Pediatrics is a primary reference for the science and practice of pediatrics and its subspecialties. This authoritative resource of original, peer-reviewed articles oriented toward clinical practice helps physicians stay abreast of the latest and ever-changing developments in pediatric medicine. The Journal of Pediatrics ranks 3rd of 70 pediatric journals receiving the most citations (Science Citation Index). The Journal is published by Elsevier, a leading global publisher of scientific, technical, and medical journals, books, and reference works. It is a member of the Reed Elsevier plc group. URL: http://www.jpeds.com

Source: SUPPLEMENT TO THE JOURNAL OF PEDIATRICS,
September 2005, Volume 147, Number 3

September 3, 2005
Ginseng modulerer immunresponset via påvirkning af cytokinproduktionen - sekundærpublikation

SEKUNDÆRPUBLIKATION

Læge Zhijun Song, 1. reservelæge Claus Moser, læge Hong Wu, stud.med. Maria Waldorff Larsen, overlæge Helle Krogh Johansen, professor Viggo Faber, forskningsleder Arsalan Kharazmi & professor Niels Høiby H:S Rigshospitalet, Diagnostisk Center, Klinisk Mikrobiologisk Afdeling og Epidemiklinikken.

Resume

Ginseng er vist at være immunmodulerende, og vi har undersøgt ginsengs påvirkning af leukocytter hos mennesker og effekt på forløbet af kronisk Pseudomonas aeruginosa -lungeinfektion i en dyremodel. Ginseng inducerede interleukin-12-produktion, og behandling af inficerede mus og rotter førte til en bedret eliminering af bakterier, mildere lungepatologi, øget fagocytaktivering og et Th1-immunrespons. Ginseng havde ingen antibakteriel effekt. Vores studier har vist, at Ginseng forbedrer forløbet af kronisk P. aeruginosa -lungeinfektion ved dets immunmodulerende effekt.

Ginseng er en kinesisk urt, der har været brugt som traditionel medicin i Kina i flere tusinde år. Der er tradition for at bruge ginseng til at hjælpe ældre og svage mennesker, fordi ginseng synes at forbedre deres velvære [1]. I moderne medicinsk forskning har man opdaget, at ginseng kan modulere funktionen af nervesystemet, kredsløbssystemet, det endokrine system og immunsystemet [1]. Derfor bliver ginseng brugt til behandling af mange forskellige sygdomme i Kina. Dog har ginseng aldrig før været brugt til behandling af bakterielle infektioner, f.eks. lungebetændelse.

Pseudomonas aeruginosa er en gramnegativ stav, som kan forårsage opportunistiske infektioner. P. aeruginosa er især problematisk for patienter med cystisk fibrose (CF), en genetisk sygdom, der er forårsaget af mutation i genet kodende for CFTR-proteinet. CFTR er en transmembran kloridkanal, der findes i eksokrine kirtler, herunder i åndedrætssystemet og fordøjelsessystemet. CF-patienter er modtagelige for P. aeruginosa-lungeinfektion [2], og hvis de først får infektionen, er det næsten umulig at udrydde bakterien, fordi den vokser i biofilm og desuden let bliver resistent over for antibiotika [2]. Behandlingen af den kroniske P. aeruginosa -lungeinfektion hos CF-patienterne er derfor kompliceret, og nye behandlingsmuligheder er ønskelige.

Forløbet af bakterielle infektioner afhænger både af den pågældende mikroorganisme og af værtens immunforsvar. Immunmodulerende behandling er derfor et vigtigt område, hvor nye behandlingsmuligheder udforskes. Immunsystemet kan groft inddeles i T-hjælper-celle type 1 (Th1) og Th2. Th1-respons stimulerer cellulær immunitet og aktiverer makrofager og Th1-celler, som producerer interferon- γ (IFN- γ ), og Th2-respons er karakteriseret af interleukin-4 (IL-4) produktion og stimulering af antistofresponset [3]. CF-patienter med kronisk P. aeruginosa -lungeinfektion er vist at have et Th2-domineret respons, mens et Th1-domineret respons synes at være korreleret til mindsket pulmonær inflammation og dermed bedret prognose [4]. En del forskning har vist, at ginseng kan modulere immunfunktionerne [1], og derfor er ginsengs indflydelse på immunsystemet blevet yderligere undersøgt på vores afdeling.

Ginsengeksperimenter in vitro

Humane leukocytter (1 × 10 7 celler/ml) blev dyrket med Gerimax ginseng solution (Dansk Droge, Ishøj, Danmark) (1-62 μ g/ml), interferon- γ og lipopolysakkarid (LPS) (2,5 μ g/ml) i forholdet 50 μ l:25 μ l:25 μ l:100 μ l [5]. Cellerne blev dyrket i 24 timer, hvorefter supernatanten blev høstet. IL-12- og IL-10-koncentrationen i supernatanterne blev undersøgt med ELISA- kits .

Resultaterne viste en signifikant forøgelse af IL-12, mens IL-10 var uforandret. IL-12 er et Th1-inducerende cytokin, mens IL-10 oftest henregnes til Th2-respons [5]. Disse resultater tyder på, at ginseng kan inducere Th1-immunrespons ved stimulering af IL-12-produktion.

Ginsengeksperimenter i dyremodeller

For at kunne etablere en kronisk lungeinfektion med P. aeruginosa i mus og rotter har det vist sig nødvendigt at indlejre bakterierne i en kunstig slim for at efterligne biofilminfektionen hos CF-patienterne. I vores laboratorium benytter vi tangalginat, som minder om bakteriernes eget alginat, som er eksopolysakkarid, der er den kvantitativt vigtigste ekstracellulære komponent i biofilmen. Syv uger gamle Lewis-hunrotter og 11 uger gamle hunmus blev brugt i eksperimenterne. Rotter og mus blev inficeret intratrakealt. Dyrene var delt op i en ginsengbehandlet gruppe og en placebobehandlet gruppe. Ginsengbehandling blev givet som subkutan injektion af 25 mg/kg til rotter eller 250 mg/kg til mus, en gang daglig i en uge (mus) eller to uger (rotter). Lungebakteriologi, lungepatologi, serumantistoffer, lunge- og miltcytokiner blev undersøgt efterfølgende.

1. Lungebakteriologi: Resultaterne viste, at ginsengbehandling signifikant bedrede dyrenes evne til at fjerne bakterierne fra lungerne i forhold til dyr, der ikke havde fået ginsengbehandling [6-8] ( Tabel 1 ).

2. Lungepatologi: Lungepatologien, vurderet ved tendens til abscesdannelse (Tabel 1) og histopatologiske tegn på akut inflammation (Tabel 1) var mindsket hos ginsengbehandlede dyr i forhold til ubehandlede dyr [6-9]. Ydermere var antallet af pulmonale mastceller signifikant lavere efter ginsengbehandling (Tabel 1) [6, 7]. Der sås mange mastceller rundt om betændelsesfokus. Mastceller er også en del af Th2-responset.

3. Serumantistofsvar: Højt antistofrespons er karakteristisk for den kroniske P. aeruginosa -lungeinfektion hos patienter med CF [2], ligesom det er karakteristisk for et Th2-domineret immunrespons. Efter ginsengbehandling blev serum-immunglobulin G (IgG) og IgG1 reduceret, mens IgG2a (et Th1-subklasse-IgG) øgedes i forhold til kontroldyrene ( Tabel 2 ) [9].

4. Aktiveringen af fagocytter: Ginsengbehandling aktiverede polymorfkernede leukocytter (PMN), monocytter og alveolemakrofager vurderet ved øget chemiluminescence og fagocytose af P. aeruginosa ( Tabel 2 ) [9, 10].

5. Lungecytokinresponset: IFN- γ , tumornekrosefaktor- α (TNF- α ), og IL-4-produktion fra muselunger og miltceller blev undersøgt hos mus, der havde P. aeruginosa -lungeinfektion med eller uden ginsengbehandling. Resultater viste et lokalt og systemisk Th1-svar (Tabel 2) [8] med højere IFN- γ , men lavere IL-4.

Sammendrag

Ginseng inducerer et Th1-respons både in vitro og in vivo, som vist ved øget IL-12-produktion fra menneskeleukocytter i celledyrkninger, øget IFN- γ , men reduceret IL-4 i dyrelunger, øget serum IgG2a, men reduceret IgG og IgG1 og et reduceret antal pulmonale mastceller sammenlignet med ubehandlede kontroldyr. Højere IFN- γ og TNF- α -produktion kan aktivere fagocytterne, hvilket fører til hurtigere fjernelse af bakterierne fra lungerne, hvilket resulterer i mildere lungepatologi. Konklusivt viser disse resultater, at ginseng kan mildne forløbet af CF-patienternes kroniske P. aeruginosa -lungeinfektion.

KIlde: Ugeskrift Læger 2005;167(33):3054-3056

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September 3, 2005
An Unexpected Reprieve

By Ben Whitford, Newsweek

Thanks to new treatments, people with cystic fibrosis now have adulthoods they could never have imagined.

When 6-month-old Tiffany was diagnosed with cystic fibrosis in 1972, her doctor warned her mother not to let her play with dolls. The girl would die before her 5th birthday, he said; why stir up maternal instincts she could not hope to fulfill? But by the time Tiffany reached 5, new treatments had arrived, and the doctors promised her a few years longer. It was to be the first of many reprieves as medical advances kept barely a step ahead of the growing girl. At 10, doctors said Tiffany would die in adolescence; at 18, she abandoned her dream of going to college because she did not expect to live to graduate. "I can't remember a time when I didn't know I was supposed to die," says Tiffany, now 33, who lives in Bradenton, Fla., with her husband, John Reid, and their three children. "But I'm still proving them wrong."

When cystic fibrosis was first diagnosed in the 1930s, 80 percent of its victims died before their 1st birthday as their bodies' mucus thickened, clogging their lungs and digestive tracts. But in the last two decades, new treatments have extended patients' life spans from months to years, and from years to decades. Cystic fibrosis is still the most lethal genetic disorder in America, affecting 30,000 people, but most sufferers now do not succumb until their mid-30s; a lucky few reach old age. With 40 percent of patients now older than 18, a new generation is living to face the challenges—both medical and emotional—of an adulthood nobody thought they would see.

The gift of life has come in installments. The extended life span of today's CF patients stems not from a single breakthrough but from a stream of minor innovations. Patients now stave off infection with a battery of different treatments: aerosols deliver increasingly potent antibiotics directly to their lungs; vibrating vests loosen their phlegm; fistfuls of enzyme supplements maintain their failing digestive tracts. "It's been an incredible success story, but we still have a lot of ground to cover," says Dr. Bruce Marshall, VP for clinical affairs at the Cystic Fibrosis Foundation. And despite new therapies targeting the deadly double-CF gene (carried in harmless single form by 10 million Americans), researchers say no decisive victory is imminent.

Doctors have sometimes been slow to realize the implications of their success. Until recently, patients in their 30s were still treated in pediatric wards, sitting in the same Winnie the Pooh chairs they had used as children. Dozens of adult centers have now opened, but the years in limbo left a mark, says Dr. Mike Knowles, codirector of the University of North Carolina's adult CF center. "Patients were sort of lost," he says. "They were not treated as if they were going to have a future, so they were not given the opportunity or responsibility to grow into mature young adults."

David Trester, a 32-year-old machine operator from Winona, Minn., blames cystic fibrosis for a youth spent drinking, fighting and racking up credit-card debt he never believed he would have to pay. "I was living in the fast lane," he says. "I didn't expect to live, so I figured, why not go out and enjoy every minute I can?" He reformed only when doctors told him potent new drugs meant he might live for decades—if his spiral into alcoholism and taste for Marlboros didn't kill him first. "As I got into my late 20s I realized, hey, I'm going to live," says Trester, who is now alcohol-free, married and expecting his first child. "I figured it was time to clean up my act."

As they embrace adult life, more and more CF patients are starting families, but the path to parenthood can be tough. Though few male CF patients can father children without expensive surgery, many young men were never told they were infertile. Female patients, in contrast, can conceive relatively easily, despite the predictions of some doctors that the disease would leave them sterile. There was initial confusion, too, over whether patients' children would inherit CF; doctors now know that transmission is impossible unless both partners carry a defective gene, and screening has become widely available only in the last decade.

And while genetic tests bring some peace of mind, prospective parents still face an agonizing dilemma. Despite medical advances, cystic fibrosis remains a fatal disease, and doctors often have to remind patients that they may not survive to raise their children. Pregnancy and sleepless nights strain patients' health, and exposure to schoolyard sniffles can trigger life-threatening infections in a parent's CF-ravaged lungs. "The easy part is getting pregnant," says Dr. Michael Boyle, director of the John Hopkins adult CF program. "Our job is to get patients to think more than nine months at a time."

For those who decide to have children, parenting can be both deeply fulfilling and bittersweet. Stacy Danko, a 40-year-old Baltimore mother of three, says she never regrets her decision; still, it's difficult watching her children, ages 14, 10 and 7, struggle to accept that their mother will die before her time. "I see their pain and it kills me," Danko says. "Your children are going to suffer as much as you do." And learning to live with that is the hardest thing of all.

See the full article at: : http://www.msnbc.msn.com/id/9193315/site/newsweek/

September 2, 2005
Scientists Determine Structure Of Enzyme That Disrupts Bacterial Virulence

The enzyme had already been shown in previous studies to significantly decrease soft rot in potato plants. The Brandeis and University of Texas team purified the enzyme and identified its structure using X-ray crystallography, an essential step toward developing drugs that may reduce the pathogenicity of bacteria involved in biowarfare threats such as glanders and diseases such as cystic fibrosis.

The enzyme works by disrupting the ability of certain bacteria to sense their own population growth -- the key to triggering genes that can increase virulence. In order to sense the size of their own populations, certain bacteria produce small molecules called N-acyl homoserine lactones. The concentrations of these lactones increase along with the growth of the bacterial population. After reaching a threshold concentration, the lactones can "turn on" a variety of genes, often increasing the virulence of the accumulating bacteria.

This population-sensing results in a type of bacterial "group think" because certain genes are not turned on until a minimum number of bacteria are present. Hence, this phenomenon is called quorum-sensing.

"Being able to disrupt quorum-sensing in these organisms could potentially augment our current treatments, and knowing the structure of this quorum-quenching enzyme will greatly help in developing more effective enzymes for this type of application," explained Walter Fast, assistant professor in the College of Pharmacy at the University of Texas at Austin.

In addition to treating plant pathogens, the hope is that these quorum-quenching enzymes may eventually be developed for use in treating human and animal pathogens that also rely on quorum-sensing for their virulence.

For example, bacterial pathogens such as Burkholderia mallei, which is responsible for the biowarfare threat glanders, and Pseudomonas aeruginosa, which often forms opportunistic infections on the lung surfaces of patients with cystic fibrosis, rely on their quorum-sensing systems to increase their pathogenicity and resistance to antibiotics.

Source: Brandeis University

August 31, 2005
Press Release
Patch investment scores resounding success with positive results from cystic fibrosis trials

Patch International Inc. (PTII: OTCBB) is extremely pleased to report that it has been informed by the management of its pharmaceutical investment, Pharmaxis (ASX: PXS, NASDAQ NM: PXSL), that excellent results from its Phase II trial, DPM-CF-201, in patients with cystic fibrosis have been received

The trial achieved its primary end point of improvement in lung function as measured by FEV(1). At the end of the two-week treatment periods, patients receiving Bronchitol had statistically significantly improved lung function compared to two weeks of placebo treatment. Spirometry was used to assess lung function.

David Stadnyk, President of PTII said, "Reaching this milestone represents a tremendous stamp of validation, and the company can look forward to the results from additional studies in the future. PTII plans to build upon this success with opportunities of greater magnitude in both the domestic and international oil and gas sectors and is looking forward to an active period of news and company development activities."

The study was a double blind, placebo controlled, radomised comparison of 420mg of Bronchitol to placebo in 49 patients with cystic fibrosis at 8 centers across Australia and New Zealand. Bronchitol or placebo was administered twice a day for 14 days in a crossover design.

Secondary endpoints of the study include quality of life measures. Significantly better respiratory symptoms were achieved among patients when taking Bronchitol compared to when on placebo. Additionally, Bronchitol had no deleterious effect on the microbiology of the sputum.

No serious adverse events were related to Bronchitol use.

Pharmaxis has received Orphan Drug status from the Food and Drug administration (FDA) for Bronchitol in cystic fibrosis.

Pharmaxis plans to present additional data from the study at the internationally important 19th Annual North American Cystic Fibrosis Conference to be held in Baltimore, MD in October.

For more information about Pharmaxis and the positive cystic fibrosis trial results, go to www.pharmaxis.com.au.

ABOUT PATCH INTERNATIONAL

PTII is a junior oil and gas producer that cur