Potential Once-weekly Asthma Treatment Found Safe, Well-Tolerated in Study
SAN DIEGO and VIENNA, Austria—September 14,
2009—Altair Therapeutics, Inc., a privately-held,
biopharmaceutical company developing novel therapeutics for
respiratory diseases, today an nounced positive results from a
phase I multiple dose safety and pharmacokinetic study of its lead
product,once-weekly inhaled AIR645 in healthy adults and mild
asthmatics. The results were presented today by Dr. Michael Hodges,
M.D., Chief Medical Officer for Altair Therapeutics at the European
Respiratory Society Annual Congress in Vienna.
AIR645 is a non-steroidal dual inhibitor of cellular responses to interleukin (IL)-4 and IL-13. These pro-inflammatory cytokines orchestrate the adaptive immune response to inhaled allergens and viruses and the development of chronic inflammation in asthma, rhinitis and other respiratory disorders. The randomized, placebo-controlled trial evaluated the safety, tolerability, bioavailability and pharmacodynamic activity of nebulized AIR645 at multiple dose levels in 32 healthy adult subjects (0.3, three, 10, and 20 mg/dose) and eight mild asthma subjects (20mg/dose). Subjects were sequentially randomized (six active: two placebo) and received six doses on study days one, three , five, eight, 15 and 22.
AIR645 was safe and well tolerated. No dose-limiting toxicities or safety signals were detected in this clinical study. Adverse effects were mostly mild and none were considered severe, significant, or serious and no subjects were discontinued due to adverse events. AIR645 exposure in sputum was found to be dose-dependent, and no accumulation of drug was evident. AIR645 half-life in sputum was calculated to be approximately 5 days. AIR645 concentration was >1000-fold higher in sputum than in plasma, indicating very low systemic bioavailability of the drug. Following repeated inhalation of AIR645 evidence of anti-inflammatory biomarker activity was seen in subjects with mild asthma (those that had baseline elevations of biomarkers), including reductions in serum total IgE, sputum eosinophils or level of 15-HETE in sputum.
"The AIR645 pharmacokinetics and distribution profile demonstrated in this study are consistent with preclinical findings and support effective once-weekly or once-daily administration of this 2'-O-methoxyethyl modified oligonucleotide in humans," commented Susan Gregory, Ph.D., Chief Scientific Officer for Altair Therapeutics. "We believe that IL-4RÎ± inhibition can prevent and retard asthma pathogenesis and will prove to be a valuable therapeutic approach to asthma, chronic obstructive pulmonary disease and other respiratory disorders."
"The safety and PK data from this study underscore the potential of AIR645 as a new, safe and effective non-steroidal anti-inflammatory control medication for asthma," said Dr. Hodges. "The dosi ng flexibility afforded by the projected long tissue half-life of this drug opens the door to improved patient compliance using a once-daily inhaler or using once-weekly nebulized formulations."
"AIR645 is based upon a proprietary anti-sense molecular design – termed ‘MOE gapmer’ – that greatly improves potency, stability, safety and tolerability in vivo," said Joel F. Martin, Ph.D., President and CEO of Altair Therapeutics. "AIR645 is the first such MOE gapmer oligonucleotide to be administered by inhalation in man and has now demonstrated favorable safety and pharmacokinetic profiles. The results are particularly remarkable because AIR645, a low cost-of-goods drug, inhibits a target that, to date, has been approachable only by expensive biologics."
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-4RÎ±). IL-4RÎ± 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.
About Altair Therapeutics
Based in San Diego, Altair Therapeutics, Inc. is a privately-held biopharmaceutical company developing novel therapeutics to treat human respiratory diseases. Altair Therapeutics’ lead product is AIR645, the first in a new class of inhaled drugs that incorporate proprietary, second-generation antisense chemistry.
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Posted: September 2009