To develop drugs for respiratory and cardiovascular diseases, GlaxoSmithKline (GSK) has entered into a worldwide exclusive agreement worth $425 million with Amira Pharmaceuticals.
The new agreement would help GSK to develop, manufacture and commercialise Amira's FLAP (5-Lipoxygenase Activating Protein) inhibitors, including AM103 and other compounds within the current development programme, for the treatment of respiratory and cardiovascular disease.
In the event that all potential development and regulatory milestones are successfully achieved, Amira could receive up to US$425 million in upfront and milestone payments. In addition, Amira will be entitled to receive tiered royalty payments based on worldwide net sales and commercial sales milestones.
Initial development activities will focus on candidate compound AM103, for the treatment of asthma. Positive data, from a phase I study completed in November 2007, show AM103 has the potential as a once-daily, oral, non-steroidal asthma treatment. In this study the compound was also well-tolerated.
The prevalence of asthma is increasing globally and despite the success of inhaled beta-agonist and corticosteroid therapy there is still a significant need for alternative therapies. Although other therapies are available that target the leukotriene pathway, a FLAP inhibitor has the potential to inhibit a broad spectrum of leukotrienes. FLAP inhibitors are also being investigated for use in other respiratory indications, including rhinitis, as well as having potential for the treatment of other inflammatory and cardiovascular diseases.
The global non-steroidal market for the treatment of asthma and rhinitis is currently worth in excess of US$ 4 billion; prescriptions for the treatment of rhinitis contribute 15 per cent to total worldwide sales of non-steroidals. A FLAP inhibitor with improved efficacy and equal or improved safety and tolerability to existing leukotriene receptor antagonists, in both asthma and rhinitis, would likely capture a significant portion of this market.
Commenting on the agreement, Dave Allen, SVP, Respiratory Centre of Excellence in Drug Discovery, GlaxoSmithKline said: "The role of anti-leukotriene agents has been well validated in the treatment of respiratory diseases. We are very excited at entering into this global agreement with Amira to deliver novel therapies to patients based on this mechanism".
FLAP (5-lipoxygenase activating protein)is a key component early in the leukotriene pathway, a complex signaling process that exerts control over biological processes, such as inflammation and immunity. Excessive production of leukotrienes exacerbates inflammatory diseases, such as asthma; the FLAP gene has also been linked to a significant increase in the risk of myocardial infarction and stroke. AM103 binds to FLAP, inhibiting the synthesis of leukotrienes that cause inflammation.
A FLAP inhibitor is active at a point higher in the leukotriene pathway than a CysLT1 receptor antagonist, enabling it potentially to inhibit the production of all leukotrienes. Leukotrienes, prostaglandins and other arachidonic acid-derived lipids make up the eicosanoid family of inflammatory mediators.
Peppi Prasit, chief scientific officer and co-founder, Amira, said, "To have identified such a positive drug candidate and progressed to the completion of phase I clinical trials just two years after the company was founded is a tremendous achievement for the team at Amira. We are delighted that GlaxoSmithKline will be taking this asset into full development. With their experience and expertise in this area we hope that AM103 will become the first FLAP inhibitor available to patients worldwide to treat symptoms of asthma and possibly other inflammatory diseases."