Altair Therapeutics Reports Successful Completion Of Phase I Study Of Inhaled AIR645

Main Category: Respiratory / Asthma
Also Included In: Allergy;  Clinical Trials / Drug Trials
Article Date: 22 May 2009 - 1:00 PDT

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Altair Therapeutics, Inc., a privately-held, biopharmaceutical company developing novel therapeutics for respiratory diseases, reported results from its phase I study evaluating the safety, tolerability and pharmacokinetics of its lead product, once-weekly inhaled AIR645, in healthy volunteers. AIR645 is a non-steroidal dual inhibitor of cellular responses to interleukin (IL)-4 and IL-13, cytokines that play a critical role in development and progression of asthma, rhinitis and other allergic disorders. Results presented today at the 2009 International Conference of the American Thoracic Society (ATS) within the Mini-Symposium "New Treatment Approaches for Asthma and Allergy" showed that inhaled AIR645 was safe, well tolerated and had dose-dependent exposure in the airways. These results demonstrate the potential of AIR645 as a convenient once-weekly treatment for asthma and other respiratory disorders. Later this year, Altair plans to initiate a phase II efficacy study in patients with asthma.

No serious or severe adverse events or dose-limiting toxicities were observed in healthy subjects exposed to single or repeated doses of AIR645. There were no changes in laboratory safety assessments, vital signs, electrocardiograms or spirometry attributed to study drug. Inhalation administration of AIR645 resulted in prolonged local exposure in the airways with a half-life in induced sputum of approximately five days and was independent of dose. Plasma AIR645 exposure was reproducibly detected only at the top doses administered (30 mg single dose arm; 20 mg multiple dose arm), suggesting very low systemic drug absorption.

"Demonstration of sustained pulmonary exposure and an excellent safety profile is an important milestone in the development of AIR645. Other drugs in this class have recently demonstrated significant efficacy following systemic administration in patients with dyslipidemia, prostate cancer and multiple sclerosis," said Michael Hodges, MD., Chief Medical Officer of Altair Therapeutics.

According to William Busse, MD, Professor and Chair, Department of Medicine, University of Wisconsin, "The cytokines IL-4 and IL-13 are key factors that may contribute to clinical aspects of asthma, including inflammation, the development of allergies, and airway hyper-responsiveness. These features make efforts to block the actions of these two cytokines an attractive target for long-term treatment of asthma. The newly released information that an inhaled antisense drug, that blocks the effects of IL-4 and IL-13, can be safely and effectively delivered to the lung is exciting and represents a significant advance in developing new treatments for asthma. Furthermore, the possibility that this product can be given once per week is also unique and affords an advantage of improving adherence and thus effectiveness."

"The AIR645 phase I safety and pharmacokinetic data and supporting preclinical pharmacology suggest that this drug may be a valuable therapeutic for asthma," said Joel Martin, Ph.D., President and CEO of Altair Therapeutics. "AIR645 utilizes the same chemical modifications and design as Mipomersen, licensed to Genzyme by Isis Pharmaceuticals and now in phase III trials for familial hypercholesterolemia."

About AIR645

AIR645 is a dual inhibitor of IL-4 and IL-13, pro-inflammatory cytokines which are implicated in the pathogenesis of asthma, allergic rhinitis and other inflammatory disorders. AIR645 is a 2'-O-methoxyethyl second-generation antisense drug targeting the mRNA that encodes the alpha subunit of the human IL-4 receptor (IL-4Rα). IL-4Rα is the signaling chain that is shared by the IL-4 and IL-13 receptors and is required for cellular responses to IL-4 and IL-13. AIR645 has the potential for less frequent administration with improved local and systemic safety. AIR645 was discovered by Isis Pharmaceuticals, Inc. (NASDAQ: ISIS) and licensed to Altair Therapeutics.

Source
Altair Therapeutics

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