GlaxoSmithKline and Myogen sign two-part hypertension partnership

A two-part Pulmonary Arterial Hypertension (PAH) collaboration between GlaxoSmithKline (GSK) (London, UK) and Myogen (Westminster, Colorado, US) has seen GSK take possession of the commercialisation rights for Myogen's ambrisentan in all territories outside the US, and Myogen take responsibility for the marketing and distribution of GSK's Flolan (epoprostenol sodium) in the US.

The ambrisentan deal pockets Myogen an upfront payment of $20m, as well as potential milestone payments amounting to $80m and stepped royalties on product sales (the estimated average royalty will be in the "mid-20% range") to reflect "the late stage development status and market potential" of ambrisentan. Myogen will remain responsible for clinical development while GSK will take on all regulatory and commercial expenses in its licensed territories.

The Flolan agreement is a three-year distribution deal that will require Myogen to build a commercial support team and field sales organisation, commencing the second-quarter of 2006, dedicated to marketing and distribution in the US. The agreement has an option for renewal upon mutual consent.

Ambrisentan is an investigational drug under development as a once-daily oral therapy for patients with PAH. Currently in Phase III development, it has been granted orphan drug designation for the treatment of PAH in both the US and EU while filing for marketing approval in both areas expected in the fourth-quarter of 2006.

It works by inhibiting endothelin, a small peptide hormone that plays a critical role in the control of blood flow and, at elevated levels, is associated with several cardiovascular disease conditions. Trial results have shown improvement in exercise capacity, time to clinical worsening, apparent survival benefit; effectiveness with once-daily dosing; potential for dose flexibility; low incidence/severity of liver function test abnormalities at all doses and no apparent drug-drug interactions with warfarin-type anticoagulants. Top-line results the ARIES-1 trial are expected in April 2006.

Flolan, approved by the FDA in 1995, is indicated for the long-term intravenous treatment of primary pulmonary hypertension and pulmonary hypertension associated with the scleroderma spectrum of disease in NYHA Class III and Class IV patients who do not respond adequately to conventional therapy. It is contraindicated for use in patients with congestive heart failure due to severe left ventricular systolic dysfunction, and in patients with known hypersensitivity to the drug or structurally-related compounds.

Both companies have said that they believe ambrisentan, "which is being developed for less severely ill PAH patients, would be complementary to Flolan, which is usually used in later stages of PAH disease".

Andrew Witty, president, Pharma Europe GSK, described the deal as "a continuation of our corporate pipeline expansion..giving GSK access to a product candidate in an indication we know very well."

J William Freytag, president and ceo, Myogen, called GSK "the ideal ex-US partner for ambrisentan", and said that he expects the Flolan agreement to "underwrite the development of our own commercial organisation, marketing and field selling expertise in PAH, well in advance of the potential launch of ambrisentan."