PARI Pharma's Nebulized DSCG Shows Results Similar to Inhaled Steroids in Asthma Studies Presented at ATS
Published: May 21, 2009
Positive Results Based on New DSCG Formulation & eFlow Technology Delivery
MUNICH and MONTEREY, Calif., May 20 /PRNewswire/ -- This week, Swiss researchers presented positive data from an ongoing Phase II clinical study at the American Thoracic Society (ATS) International Conference that compared PARI Pharma's inhaled IsoCrom, an isotonic 1% disodium cromoglycate (DSCG) solution, to inhaled corticosteroids (ICS) in 28 children with atopic asthma. Results showed decreases in mean asthma symptom scores without a change in lung function for both groups. These results were achieved with IsoCrom administered via a customized small droplet Investigational eFlow Nebulizer System designed to deliver drugs to the deep lungs. One of the benefits of DSCG is the long track record as an extremely safe drug.
Given the preliminary results of the ongoing Phase II trial, treatment with IsoCrom inhaled via a small droplet (MMAD ~ 3.3 microns) Investigational eFlow Nebulizer System has similar effects on asthma control, symptoms, lung function, and FeNO levels as compared to ICS in children with allergic asthma.
"IsoCrom was well tolerated in all children when administered via the Investigational eFlow Nebulizer System," said Prof. Johannes Wildhaber, principal investigator of the study sponsored by the Swiss Pediatric Society.
"These encouraging data may be due to the hygroscopic nature [the ability to attract water molecules] of DSCG, and its tendency to grow in size upon inhalation when administered via a dry powder or metered dose inhaler (DPI or MDI). This assumption is supported by in-vitro study results previously published by PARI Pharma and other studies demonstrating that chymase-positive mast cells primarily located in the distal lungs play a crucial role in asthma. This requires delivery of DSCG via small droplets to the target site in the lungs and can be best achieved by a highly efficient nebulizer, such as the customized small droplet generating eFlow electronic nebulizer," stated Dr. Alexander Moeller, head of the Research Division, Respiratory Medicine at the University Children's Hospital Zurich, Switzerland.
Previous DSCG therapies were only moderately effective, since the interaction of the very hygroscopic properties of DSCG with the drug delivery system were not understood.
"We believe our novel, higher concentrated, low volume DSCG formulation delivered via an optimized Investigational eFlow Nebulizer System opens new treatment avenues and perspectives for patients and physicians. This expectation is further supported by newly published data on a potential antiviral efficacy of DSCG that may be particularly important in the treatment of pediatric asthma," added Dr. Manfred Keller, chief scientific officer and executive vice president of PARI Pharma.
At ATS, PARI Pharma also presented in-vitro data comparing IsoCrom (1%) with a novel, higher concentrated (6%), low volume DSCG formulation that requires significantly less nebulization time than IsoCrom. The results of this in-vitro study using 45mg/0.75ml may allow the option for twice-daily administration in less than 2.5 minutes.
IsoCrom & ICS Comparative Study Results
Data from a randomized, open-label, Phase II, six-month study comparing efficacy and safety of an IsoCrom solution versus inhaled steroids was presented by researchers from the pediatric department of the University Hospital Zurich, Switzerland. Twenty eight children (11.9 +/- 2.8 years) with stable atopic asthma were randomized to inhale either IsoCrom, delivered at a dose of 60 mg per day administered in three inhalations of 2ml using a customized small droplet Investigational eFlow Nebulizer System, or inhaled corticosteroids (ICS) without dose adjustments administered in two inhalations using a metered dose Inhaler (MDI) via a holding chamber.
The study compared various lung function parameters, such as forced expiratory volume in 1 sec (FEV1), forced vital capacity (FVC), mean expiratory flow (MEF 50% pred), inflammatory markers, such as serum percent Eosinophils and expired nitric oxide (FeNo), asthma symptom scores, required beta agonist use, and cortisol levels. The mean asthma symptom score decreased significantly in both treatment groups over the 6 month treatment period from 5.2 +/- 2.5 to 3.07 +/- 2.2 (p=0.021) for the ICS cohort and from 5.6 +/- 1.5 to 3.2 +/- 1.9 (p <0.001) for the IsoCrom group, respectively. No significant change in lung function was observed during the six-month treatment with either inhaled corticosteroids or IsoCrom.
PARI's Comparative in-vitro assessment of IsoCrom & a novel 6% DSCG formulation
Sophisticated aerodynamic droplet and particle size assessments in a cascade impactor operated at different humidity levels revealed how delivery and deposition performance of aerosols can be affected. In-vitro breath simulation tests mimicking breathing patterns of 3 and 10 year old children demonstrated drug delivery performance is nearly unaffected when electronic eFlow Technology nebulizers were used for inhalation. The novel 6% DSCG solution may also offer new therapeutic perspectives due to the combined anti-asthmatic and antiviral potency of DSCG.
"Since the relevance of mast cells in lung vascular remodeling and the development of pulmonary hypertension was also demonstrated in an ATS paper by researchers from Canada, Finland and Germany, nebulized DSCG may also be explored as a new therapeutic for the treatment of pulmonary hypertension," stated Dr. Wolfgang M. Kuebler, professor of vascular physiology and pathophysiology at the Charite University Hospital, Berlin, Germany and associate professor at the Department of Surgery of the University of Toronto, Canada.
About PARI Pharma's novel 6% DSCG Formulation
PARI's high concentrated isotonic DSCG formulation is an investigational proprietary aqueous solution of 6% DSCG with excipients already approved for inhalation. It is designed to be delivered via an optimized, small-droplet Investigational eFlow Nebulizer System or via PARI's paranasal drug delivery system, VibrENT. This provides the potential for the treatment of lower and upper respiratory diseases, such as asthma or sinusitis.
About the Investigational eFlow Nebulizer System and eFlow Technology
The Investigational eFlow Nebulizer System uses eFlow Technology to enable highly efficient aerosolization of liquid medications via a vibrating, perforated membrane that includes thousands of small holes that produce the aerosol mist. Compared to other nebulization technologies, eFlow Technology produces 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 period of time. Combined with its silent mode of operation, small size (it fits in the palm of your hand), light weight, and battery use, products incorporating eFlow Technology reduce the burden of taking daily, inhaled treatments. The Investigational eFlow Nebulizer System and eFlow Technology are proprietary to PARI Pharma.
About PARI Pharma
PARI Pharma focuses on the development of aerosol delivery devices, drug formulations, and inhaled drug therapies. Based on PARI's 100-year history working with aerosols, PARI Pharma develops treatments for pulmonary and nasal administration optimized with advanced delivery technologies, such as eFlow Technology. PARI Pharma partners with pharmaceutical companies to develop new or improved therapies with eFlow Technology and other advanced delivery platforms. Investigational eFlow Nebulizer Systems are optimized and customized per investigational drug product and are currently in clinical trials for cystic fibrosis, asthma, COPD, respiratory syncytial virus (RSV) infection, and treatments for lung transplant patients among other indications.
PARI Pharma provides comprehensive inhalation drug development, including nebulizer formulation development and optimization, analytics, aerosol characterization, clinical protocol development, and regulatory guidance, all in compliance with CMC/GCP guidelines. PARI Pharma has several clinical development programs ongoing, either partnered or on its own. PARI Pharma, a PARI Medical Holding company, is located in Munich, Germany with a major presence in the United States. Online at www.paripharma.com
CONTACT: Additional information on eFlow Technology and pharmaceutical
development is available by contacting Kirsten Ayars, +1-805-452-7909, or
Geoff A. Hunziker, +1-831-372-3580, or Dr. Robert Phelps, +49 89 742846-69
Web site: http://www.paripharma.com/