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Data increase confidence in the Horizon development programme
London, UK | February 4, 2009 | GlaxoSmithKline (GSK) and Theravance, Inc. (NASDAQ: THRX) today announced positive results from three, separate phase 2b studies assessing efficacy and safety of GSK’s inhaled corticosteroid (ICS) fluticasone furoate (FF or GW685698) across a range of eight doses (25 – 800 mcg) in over 1,800 patients with mild, moderate and severe asthma. Once-daily FF produced statistically significant improvements in patients’ lung function (trough FEV1) compared to placebo (p<0.05) in each of the three study populations and at all doses, with the exception of the very lowest dose tested. In all studies numerically greater improvements in lung function were observed with a lower total daily dose of FF compared to fluticasone proprionate (FP).
“The strong results from these three studies demonstrate that fluticasone furoate shows promise as an efficacious, once-daily ICS. Additionally, the consistent responses seen demonstrate the robust nature of these data,” commented Darrell Baker, SVP GSK Respiratory Medicines Development Centre. “These outcomes, combined with the positive findings from the recent studies of the long-acting beta agonist (LABA) ‘444, bring us a step closer to selecting the appropriate doses of FF and ‘444 for future studies and increase the potential of this combination to be a significant, once-daily treatment for asthma and COPD. This is, of course, particularly important for those patients where compliance and asthma control are difficult.”
“We are delighted by the outcomes of these studies,” said Rick E Winningham, CEO, Theravance. “The compelling results give us continuing confidence in the Horizon clinical development programme and improve our understanding of the efficacy and safety of FF. We are moving closer to achieving our objective of delivering effective, once-a-day inhaled medicines to patients with asthma and COPD.”
The three dose-ranging studies fully characterised FF’s dose response curve, with only the lowest dose (25 mcg) showing no statistically significant difference from placebo on the primary efficacy endpoint (trough FEV1) and with only the highest dose (800 mcg) associated with a statistically significant reduction in urinary cortisol levels (a known side effect of inhaled corticosteroids). FF was well tolerated throughout the course of the eight-week treatment period across the three studies. Adverse events occurred at a similar or lower frequency than FP in each study, with the most common adverse event being headache. A low frequency of serious adverse events occurred on all treatments, including placebo, FP and FF, and for FF were not dose dependant.
Study design
Patient populations with varying severities of asthma were randomised in three separate double-blind, double-dummy, placebo-controlled studies. In each study, patients aged 12 years and older received one of four doses of FF once daily, placebo or FP twice daily. FF was administered via a novel single step activation inhaler and FP was administered via DISKUS®. All patients were permitted to use a short-acting beta-agonist (albuterol) as rescue medication to relieve symptoms of asthma as needed.
The dosing regimen for each study was as follows:
Mild asthmatic population: 601 patients with persistent asthma, symptomatic on short-acting beta-agonist asthma therapy with no use of inhaled corticosteroid were randomised to receive 25, 50, 100 or 200 mcg once daily, FP 100 mcg twice daily or placebo.
Moderate asthmatic population: 622 patients with persistent asthma, symptomatic on low-dose ICS were randomised to receive 100, 200, 300 or 400 mcg once daily, FP 250 mcg twice daily or placebo.
Severe asthmatic population: 627 patients with persistent asthma, symptomatic on moderate-dose ICS were randomised to receive 200, 400, 600 or 800 mcg once daily, FP 500 mcg twice daily or placebo.
The primary endpoint to assess efficacy was mean change from baseline to the end of the eight week treatment period in trough (measured 24 hours after the last dose) forced expiratory volume (FEV1).
The Horizon programme
Overall the Horizon programme has enrolled in excess of 3,000 asthma and COPD patients globally. Positive data from two phase 2b studies with the LABA ‘444 in asthma and COPD were reported at the end of 2008. Enabling studies involving '444 and FF given in combination are ongoing.
GlaxoSmithKline – one of the world’s leading research-based pharmaceutical and healthcare companies – is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For further information please visit www.gsk.com.
Theravance – is a biopharmaceutical company with a pipeline of internally discovered product candidates. Theravance is focused on the discovery, development and commercialization of small molecule medicines across a number of therapeutic areas including respiratory disease, bacterial infections and gastrointestinal motility dysfunction. The company’s key programs include: telavancin for the treatment of serious Gram-positive bacterial infections with Astellas Pharma Inc., the Horizon program and Bifunctional Muscarinic Antagonist-Beta2 Agonist (MABA) program with GlaxoSmithKline plc, and the Gastrointestinal Motility Dysfunction program. By leveraging its proprietary insight of multivalency toward drug discovery focused primarily on validated targets, Theravance is pursuing a next generation strategy designed to discover superior medicines in areas of significant unmet medical need. For more information, please visit the company's web site at www.theravance.com. THERAVANCE®, the Theravance logo, and MEDICINES THAT MAKE A DIFFERENCE® are registered trademarks of Theravance, Inc.
SOURCE: GlaxoSmithKline |
