GlaxoSmithKline (GSK) and Amicus Therapeutics,  a biopharmaceutical company at the forefront of developing therapies for rare diseases, have expanded their collaboration to develop and commercialise the investigational pharmacological chaperone migalastat HCl for Fabry disease.

The expanded alliance comprises three components: Co-development of all current and future formulations of migalastat HCl for Fabry disease, including a co-formulation of migalastat HCl with GSK/JCR Pharmaceutical Co., Ltd’s investigational enzyme replacement therapy (ERT) for Fabry disease; Commercialisation arrangements for all future Fabry products. Amicus will have commercial rights to all Fabry products in the United States and GSK will commercialise all products in the rest of world; Increased GSK ownership in Amicus with an $18.6 million investment in common stock priced at $6.30 per share, bringing GSK’s total ownership stake in Amicus to 19.9 per cent.

“We have strengthened our relationship with Amicus through the expanded Fabry collaboration and additional equity investment in the Company,” said Marc Dunoyer, Global Head of GSK Rare Diseases and a member of the GSK Corporate Executive Team. “Amicus has a very successful track record as our development partner and long-standing relationships with the Fabry community and we look forward to their leadership in the US commercialisation of several potential new medicines for patients with Fabry disease. This is an important step in our strategic vision, allowing us to undertake and fund an enlarged scientific program with a view to turning molecules into medicines for rare diseases faster and more effectively than ever before.”

The global Fabry collaboration combines Amicus’ US presence, pharmacological chaperone development expertise, and established relationships in the rare and orphan disease community with GSK’s global rare disease unit and worldwide regulatory, commercial, and manufacturing capabilities. Amicus and GSK are now committed to the parallel development of three different uses of migalastat HCl for Fabry disease:

Phase III global registration studies (Study 011 and Study 012) are currently underway in patients with genetic mutations that are amenable to chaperone monotherapy. Results from Study 011 are anticipated in the third quarter of 2012 to support a New Drug Application (NDA) submission to the US Food and Drug Administration (FDA). If approved, Amicus will be responsible for the US commercial launch.

A phase II study of migalastat HCl co-administered with ERT for Fabry disease (Study 013) is currently ongoing. In January 2012, Amicus announced positive preliminary results from Study 013.

Amicus and GSK, in collaboration with Japan-based JCR, are developing migalastat HCl co-formulated with a proprietary recombinant human alpha-Gal A enzyme (JR-051). This ERT was developed by JCR and licensed to GSK for all markets outside Japan. Preclinical studies conducted by Amicus, GSK and JCR suggest that this co-formulated chaperone-ERT product may provide greater alpha-Gal A enzyme uptake into tissue and markedly reduced levels of GL-3 in Fabry disease-relevant tissues compared to recombinant enzyme alone. Amicus and GSK believe that this co-formulated chaperone-ERT product for Fabry disease has the potential to enter clinical studies in 2013.

John F Crowley, chairman and CEO of Amicus, said, “GSK has added significant value to the Fabry programme through its global scale and capabilities as well as the dedicated focus of GSK Rare Diseases. Through our expanded agreement, GSK is increasing its investment in the Fabry development programme and Amicus is transforming into a commercial-stage biopharmaceutical company within the US Amicus is leveraging its chaperone-ERT platform to advance migalastat HCl in multiple potential uses for patients with Fabry disease.”

Key Highlights of the collaboration:

Amicus will commercialise all formulations of migalastat HCl in the US, while GSK will commercialise in the rest of the world.

Amicus and GSK will continue to share research and development costs for all formulations of migalastat HCl, with Amicus funding 25 per cent and GSK funding 75 per cent of these costs for monotherapy and co-administration during the remainder of 2012. Amicus and GSK will be responsible for 40 per cent and 60 per cent of these costs, respectively, for co-formulation immediately and for all formulations in 2013 and beyond.

GSK will make an $18.6 million equity investment in Amicus, bringing GSK’s total ownership stake in Amicus to 19.9 per cent. GSK will purchase 2,949,581 shares of common stock at $6.30 per share, a seven per cent premium over the 15-day average closing sale price of Amicus’ common stock as reported by Nasdaq.

Amicus will receive a $3.5 million cash payment from GSK this quarter to reflect Amicus’ achievement of a clinical development milestone during the second quarter 2012.

GSK will be eligible to receive US regulatory approval and product launch milestones totaling $20 million for migalastat HCl monotherapy and chaperone-ERT co-administration.

GSK will be eligible to receive additional regulatory and time-based milestone payments totaling up to $35 million within seven years following the launch of a co-formulated chaperone-ERT product. Amicus will also be responsible for certain additional pass-through milestone payments and single-digit royalties on the net US sales of the co-formulated chaperone-ERT product that GSK must pay to a Third Party.

Fabry disease is an inherited lysosomal storage disease that is currently estimated to affect approximately 5,000 to 10,000 people worldwide. Fabry disease is caused by deficiency of an enzyme called alpha-galactosidase A (alpha-Gal A). The role of alpha-Gal A within the body is to break down a complex lipid called globotriaosylceramide (GL-3). Reduced or absent levels of alpha-Gal A activity leads to the accumulation of GL-3 in the affected tissues, including the central nervous system, heart, kidneys, and skin. This accumulation of GL-3 is believed to cause the various symptoms of Fabry disease, including pain, kidney failure, and increased risk of heart disorders and stroke.