Altair Therapeutics, Inc., a privately-held, biopharmaceutical company developing novel therapeutics for respiratory diseases, today announced 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-4Rα 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 dosing 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.”
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