Date: 2013-11-20
Type of information: Licensing agreement
Compound: migalastat HCl
Company: GSK (UK) Amicus Therapeutics (USA - NJ)
Therapeutic area: Rare diseases - Genetic diseases
Type agreement: licensing
development
commercialisation
Action mechanism: Migalastat hydrochloride is a pharmacological chaperone. It is intended to bind to abnormal alpha-galactosidase A (alpha-Gal A) and recover native protein folding, allowing correct transportation to the lysosome and restoring protein activity. This would provide an alternative to enzyme replacement therapy for the treatment of Fabry disease. In phase III clinical trials, migalastat hydrochloride is administered orally at 150mg once every other day.
Disease: Fabry disease
Details: * On July 17, 2012, GSK and Amicus Therapeutics 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%.
The global Fabry collaboration combines Amicus’ U.S. 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:
• Migalastat HCl monotherapy in Phase III: 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 FDA. If approved, Amicus will be responsible for the US commercial launch.
• Migalastat HCl co-administered with ERT in Phase II: 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.
• Migalastat HCl co-formulated with a proprietary preclinical ERT: 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.
Financial terms: GSK will make an $18.6 million equity investment in Amicus, bringing GSK’s total ownership stake in Amicus to 19.9%. GSK will purchase 2,949,581 shares of common stock at $6.30 per share, a 7% 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.
Latest news: * On November 20, 2013, GSK and Amicus Therapeutics have announced that Amicus has obtained global rights to develop and commercialise migalastat HCl as a monotherapy and in combination with enzyme replacement therapy (ERT) for Fabry disease. Amicus will have sole rights to the global drug development, regulatory and commercial activities for the next-generation Fabry ERT (migalastat HCl co-formulated with ERT) as well as migalastat HCl monotherapy. GSK will be eligible for future regulatory and commercial milestone payments, as well as royalty payments. GSK will further invest $3 million in Amicus through an equity investment in a concurrent private placement in public equity transaction
Under the terms of the revised agreement, there is no upfront payment from Amicus to GSK. For the next-generation Fabry ERT GSK is eligible to receive single-digit royalties on net sales in eight major markets outside the U.S. For migalastat HCl monotherapy, GSK is eligible to receive post-approval and sales-based milestones as well as tiered royalties in the mid-teens in eight major markets outside the U.S. The terms of the revised agreement replace the prior agreement in its entirety. Under the prior agreement entered into in July 2012, Amicus and GSK were co-developing migalastat HCl globally and GSK had rights to commercialise migalastat HCl outside the United States.
