Amicus Therapeutics' shares surged as much as 40 percent Wednesday after the company announced positive results from a Phase III trial testing its oral Fabry disease drug candidate migalastat against Sanofi's Fabrazyme (agalsidase beta) and Shire's Replagal (agalsidase alfa), the current standard-of-care enzyme replacement therapies (ERTs), both of which require bi-weekly infusions. The company indicated that it now plans to submit migalastat for European approval early next year, and will meet with FDA officials to determine whether results from Study 012, as well as those from the late-stage Study 011, for which it reported positive 12- and 24-month results in April, are sufficient for approval.
Study 012 involved 60 Fabry disease patients with amenable mutations who were treated for at least 12 months with Fabrazyme or Replagal prior to enrollment. Participants were randomised to receive migalastat monotherapy or remain on ERT for 18 months, after which patients in the ERT arm were eligible for treatment with migalastat for an additional 12 months. The co-primary endpoints were mean annualised changes in estimated glomerular filtration rate (eGFR) and measured GFR (mGFR) assessed by descriptive comparisons of migalastat and ERT over 18 months.
Study results illustrated that migalastat efficacy was comparable to ERT as measured by the change in eGFR and mGFR, and was also"generally safe and well-tolerated." Amicus noted that levels of plasma lyso-Gb3, a biomarker of Fabry disease, remained low and stable in patients who were switched from ERT to migalastat. Further, the company said that among 48 patients who completed the study, 45 remain on migalastat as their only treatment for Fabry disease.
Study leader Raphael Schiffmann said the data "show a positive treatment effect of migalastat in Fabry patients with amenable mutations," adding that "when combined with the favourable safety profile, the totality of the data from Study 012 and Study 011 indicate that migalastat should become an important new oral treatment option for Fabry patients." With regard to the potential size of the market, CEO John Crowley cited the company's assessments of over 550 known Fabry mutations, saying "we have good evidence to support that at least 30 percent of Fabry patients have amenable mutations." Further, data from newborn screening studies "[suggest] that up to 50 percent of the overall Fabry population could be amenable to migalastat monotherapy," he added.
Commenting on the news, Janney Montgomery Scott analyst Kimberly Lee said the data from Study 012 significantly increases migalastat's chances of approval and also makes Amicus a potential takeover target, including by Sanofi and Shire, with bids at a 30- to 40-percent premium. Cowen and Co. analyst Ritu Baral predicted a European launch for migalastat in 2016, with the US following suit the year after. Meanwhile, Lee estimated the drug would be priced at $200 000 per patient annually if approved, generating peak sales of $400 million worldwide.
In 2012, Amicus and GlaxoSmithKline reported six-month Study 011 results showing that migalastat had failed to significantly improve the proportion of patients achieving at least a 50-percent reduction in kidney interstitial capillary globotriaosylceramide levels. Amicus later said it would delay an FDA filing while it awaited "all of the Phase III datasets" for the drug. GlaxoSmithKline has since returned the rights to migalastat, as well as a next-generation Fabry disease ERT, back to Amicus.
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