Aridol™ for asthma and COPD
Bronchitol™ for bronchiectasis, cystic fibrosis and COPD
Aridol has been accepted for evaluation in a major US asthma management study run by the U.S. Asthma Clinical Research Network (ACRN), involving 360 subjects. The study received an investigator-initiated IND from the FDA and is running in parallel with a National Institute of Health (NIH) funded trial to determine the best therapy adjustment strategy for asthma patients over the long term. The ARCN study’s aims are to evaluate Aridol’s ability to characterize asthma phenotypes, predict asthma control and exacerbations, and predict responses to interventions. It is being run in 10 of the largest asthma clinical research centres in the U.S. and will examine whether Aridol can be used to improve outcomes in asthmatic patients by guiding therapy.
Korea is the first Asian country in which Pharmaxis has filed a New Drug Application, and was chosen because of the high patient numbers and acceptance of bronchial provocation tests in diagnosing and managing respiratory disease.The Korean regulatory approval process is expected to complete in Q1 2008, after which Pharmaxis would seek reimbursement approval through the national health scheme.
Korea has an estimated 2.5 million asthma sufferers with 7 — 15% of asthma patients currently being referred for a bronchial challenge test and represents an important base from which to launch Aridol into the Asian market.
Aridol supplied to US pharmaceutical marketA U.S. pharmaceutical company has placed an order to purchase Aridol™ test kits for a series of asthma trials evaluating its new asthma therapeutic. The phase II trials will be conducted in North America and are expected to commence later this year. Since Pharmaxis expanded its GMP-approved facility and made available a new clinical trial kit, the number of studies has risen to more than 60 worldwide, most initiated by key opinion leaders in respiratory medicine. Aridol can be supplied to companies wishing to conduct clinical trials by referencing the IND granted by the U.S. FDA in 2005.
In June 2007, 13 European countries involved in the Mutual Recognition Procedure issued a marketing authorization for Aridol. The registration marks the successful culmination of a significant drug registration process by Pharmaxis and follows Sweden’s acceptance of Aridol late in 2006. Aridol is the first lung challenge test to be approved Europe-wide.
The 13 approving countries include Germany, France, the United Kingdom, Italy, the Netherlands, Belgium, Denmark, Greece, Spain, Finland, Ireland, Norway and Portugal. Aridol is already being marketed in Sweden and Australia. Distribution partners have been established for most major markets, with furtherdistributors pending. Pharmaxis distributes Aridol directly to physicians in the UK and Australia.
Aridol endorsed in global guidelines
Aridol has been included in two influential guidelines: the GINA Report on Global Strategy for Asthma Management and Prevention, and the Australian Asthma Management Handbook. Aridol is recommended in both guidelines as a lung function test that physicians can undertake to diagnose asthma in patients. The Global Initiative for Asthma (GINA) is a network of individuals, organisations and public health officials who disseminate information about the optimal care of patients with asthma, incorporating the latest research and best clinical practice. The report responds to recent international studies highlighting that asthma control remains poor, and promotes an approach to asthma management based on asthma control, rather than asthma severity.
Published as the National Asthma Council Australia’s Asthma Management Handbook, the guidelines are the gold standard of practice for asthma management in Australia. They are updated regularly to accommodate changes in asthma management, based on the latest medical evidence and new treatments that become available, as well as reflecting current areas of consumer concern.
Aridol registered by the Australian TGA
On March 23 2006, the Australian regulatory body, the Therapeutic Goods Authority (TGA) registered Aridol to identify bronchial hyperresponsiveness to assist in the diagnosis of asthma. This represents the culmination of over 10 years work by a large number of people—from the scientists at the Royal Prince Alfred Hospital, Sydney, to the preclinical, clinical and regulatory teams — the registration of Aridol is a significant outcome for all involved.
The TGA re-issued the existing GMP (Good Manufacturing Practice) licence to manufacture. Aridol is now manufactured for commercial sale in Australia and other parts of the world.
For the registered Product Information and other details, please see www.Aridol.info
In December 2005, the first patient enrolled in a US-based Phase III trial required for registration of Aridol in the USA. In August 2006, the last patient for the trial was recruited, and the results were released in November 2006.The FDA approved the protocol for the trial which was conducted at 30 U.S. centres.It enrolled more than 500 patients who were suspected of having asthma but who did not have a firm diagnosis. Based on this study and the earlier Australian Phase III trial that was the basis of the marketing approval in Sweden and Australia, Pharmaxis plans to file a New Drug Application (NDA) with the U.S. Food and Drug Administration (FDA) in the second quarter of 2007.
Within the group of patients with predominantly very mild symptoms, Aridol was able to identify exercise induced bronchoconstriction in 58% of cases (sensitivity).In comparison methacholine, an approved lung function test in the U.S., identified 54% of cases.The difference between the two tests was not statistically significant.Aridol also had similar specificity to methacholine, (66% versus 70% respectively) in subjects without exercise induced bronchoconstriction.In addition Aridol was proven to have an acceptable safety profile.The result underscores that there is no gold standard with which to compare Aridol and confirms that it performed as well, or better, than an existing FDA approved test.
Aridol Phase III study in Australia successful In late 2004, we completed the largest clinical trial undertaken by an Australian company. In the trial, Aridol™ correlated well with patients diagnosed as asthmatic by an expert physician. Importantly, preliminary analysis of the Aridol™ test results also suggests that 25 per cent of the asthmatic patients studied should have their medication increased or changed to improve control of their disease, and up to 17 per cent could have their medication decreased without adverse effects.The Phase III, open label, blinded, randomised cross-over trial commenced in January 2004, and studied 646 sthmatic and non-asthmatic patients aged from 6 to 83 years, at 12 hospitals across Australia. This successful completion of the study allows a marketing application to be submitted in Australia and Europe.
Refer to the Guide to Clinical Trials, Regulation and Approvals process for an overview.
Clinical trial data to date supports the accuracy of Aridol™ in diagnosing asthma with high sensitivity and specificity for active asthma, with a dose response curve that allows assessment of disease severity. Based on available results, doctors will be able to perform this test on first visit from a patient with symptoms suggestive of asthma, and produce a diagnosis normally without the need for further tests. The patient will get immediate feedback on their condition and whether they have mild, moderate or severe disease.
In addition, preliminary data indicates the possibility of Aridol™ being a useful tool for:
Worldwide medical interest in Aridol™ is growing, with doctors in the UK, US, Canada and Switzerland preparing to undertake further patient testing of Aridol™.
Clinical trials involving Aridol™
Bronchitol for cystic fibrosis completes FDA Special Protocol Assessment
Bronchitol completes SPA for cystic fibrosis
Pharmaxis and the U.S. Food and Drug Administration (FDA) have reached agreement under the Special Protocol Assessment process (SPA) on the design of a pivotal Phase 3 trial of the mucus clearing agent, Bronchitol, in patients with cystic fibrosis.The SPA process provides an agreement that the study design, including trial size, clinical endpoints and/or data analyses are acceptable to the FDA.When complete, positive results will form the primary basis of an efficacy claim in support of a New Drug Application.The randomized, double-blind Phase III clinical trial treats approximately 250 adults and children for 26 weeks, and assesses improvements in pulmonary function, infectious episodes and quality of life.
Phase III trial finds Bronchitol effectiveThe Phase III study of Bronchitol for bronchiectasis (B301), has met its two primary efficacy endpoints: quality of life and mucus clearance. Data from the 362 subject study demonstrated a highly significant improvement in quality of life after 12 weeks of treatment with Bronchitol as assessed by the St George Respiratory Questionnaire, (p-value less than 0.005) and a significant improvement in quality of life compared to placebo (p-value less than 0.05). Additionally, there was a highly significant difference in mucus clearance at 12 weeks for patients receiving Bronchitol versus those patients receiving placebo (p-value less than 0.001).There were no serious adverse events attributable to treatment and the incidence of adverse events did not significantly differ between the placebo and the Bronchitol groups. The trial was conducted at 22 hospitals across Australia, New Zealand and the United Kingdom.
Bronchitol Phase III trial in bronchiectasis closesThe last of 362 subjects completed the efficacy phase of its global Phase III clinical trial of Bronchitol in bronchiectasis in May, 2007. Participants received either Bronchitol or placebo for three months, at which point the effect of treatment was assessed. An extension of the trial allows participants access to Bronchitol for a total of twelve months to determine the safety of long term Bronchitol treatment. This second component of the trial is fully recruited and will complete in 2008.
The outcome from the trial will be available in Q3, 2007, after the individual patient data has been checked, the study unblinded and the statistical analysis completed. A positive outcome from the study will enable Pharmaxis to seek approval to market Bronchitol.
Bronchitol Phase III trial in cystic fibrosis beginsThe first patient in an international Phase III clinical trial evaluating Bronchitol in cystic fibrosis sufferers was randomized in April, 2007. The trial is being conducted in up to 40 hospitals across Australia, the UK and Ireland, and is the final clinical step before Pharmaxis seeks approval to market Bronchitol for cystic fibrosis in the European Union, Australia and elsewhere.
The trial design has been constructed following consultation with the European and Australian regulatory agencies and will assess the effectiveness and safety of Bronchitol in treating cystic fibrosis. The Phase III clinical trial includes a 26-week efficacy treatment period, followed by a 26-week safety extension period. The efficacy component of the trial is a randomized, double-blind investigation of Bronchitol twice daily in approximately 250 patients with cystic fibrosis. The trial is enrolling cystic fibrosis patients aged six years and above. Participants will be assessed for improvements in lung function, infectious episodes and quality of life.
Bronchitol in cystic fibrosis trial in children closes enrollmentA Phase II clinical trial of Bronchitol in children with cystic fibrosis has closed its enrollment phase. The study is an independent investigator-initiated study being conducted at two sites in the United Kingdom, has enrolled 25 subjects. The original target of 42 set by the investigator was revised downwards following a review of the trial and because of a shortage of volunteers at the two UK sites. The trial is not on the regulatory approval path, but is an important study for children with cystic fibrosis. Children enrolled in the trial are completing three months’ treatment with each of three different therapies — Bronchitol alone, both Bronchitol and rhDNase together and rhDNase alone.(rhDNase is marketed as Pulmozyme, which is a trade mark of Genentech.) The trial will measure changes in lung function, airway inflammation, infections and quality of life, and is expected to conclude in 2008.
II Trial in COPD/Bronchiectasis completedA 60 patient Phase II clinical trial has been completed in Australia and New Zealand in volunteers with bronchiectasis, with the results released in September 2004. The trial was very successful and demonstrated that Bronchitol™ had a major impact on improving the quality of life for people suffering with bronchiectasis.
This is the first time anywhere in the world that a new drug has shown to be of benefit for people with this disease. Most encouraging was the unsolicited feedback from people who had participated in the trial. Many of the participants have asked us to accelerate the development program and ensure this important product is brought to market as quickly as possible. We are responding to this request and expect to start the final pre-registration trials in the first half of next year.
The results from this study are being prepared for publication and position Bronchitol in a unique class.We are now working with key international respiratory physicians and eagerly await the commencement of the new study.
This multi-centre Phase II study across Australia and New Zealand in patients with cystic fibrosis has reached its recruitment target. The primary objective of the study is to improve quality of life and the lung function of patients following two weeks of treatment. The study is expected to report during mid 2005.Refer to the Guide to the Clinical Trial, Regulation & Approvals Process for an overview of the process.
PXS25/64 was under development for the treatment of immune diseases such as multiple sclerosis and rheumatoid arthritis. Our earlier pre-clinical work has shown that a modified version of PXS25, PXS64, has greatly improved oral absorption over the original compound. Recent results indicate that clinical proof-of-concept for PXS25 and PXS64 may be more readily evaluated in inflammatory diseases other than multiple sclerosis. We are exploring these avenues with further pre-clinical efficacy studies in models of asthma and other inflammatory lung conditions. In parallel, we are optimising the manufacturing process and are undertaking significant safety studies in preparation for human trials in healthy volunteers, which are now projected for 2008.
PXS2076 and PXS74
Both compounds have shown promising activities in models of arthritis and asthma, however, neither compound has the robust properties required for development as a pharmaceutical. We are currently working on identifying a therapeutic target for PXS2076 and on improved variants of PXS74.
This page last updated on 28 November 2007
