Shire has surprised observers by pulling its file in the USA to get approval for its Fabry disease drug Replagal.
The Ireland-headquartered firm has withdrawn its Biologics License Application for Replagal (agalsidase alfa) with the US Food and Drug Administration. Shire says that recent interactions with the latter “have led the company to believe that the agency will require additional controlled trials for approval”.
Such studies “would cause a significant delay, and an approval of Replagal for US patients would only be possible in the distant future”, the company added. It noted that no concerns over the safety profile of the product, which has been approved in Europe for over ten years, were raised by the FDA.
Shire is pretty miffed by the stance taken by the FDA given that in 2009, and again in 2011, the agency actually encouraged the firm to submit an application for Replagal. The company has been in ongoing dialogue with the agency since the supply shortage caused by manufacturing problems of Genzyme Corp’s Fabrazyme (agalsidase beta), the only US-approved treatment for Fabry disease which surfaced in 2009.
The information in the BLA included “relevant updates such as manufacturing and open long-term clinical trial data”, Shire says, adding that it expected “a quick review process and eventual approval” after providing US patients with Replagal on an emergency basis, “a therapy they desperately needed at the time”.
Sylvie Gregoire, president of Shire HGT (the firm’s business unit focused on genetic diseases), noted that the company “has had a close partnership with the global Fabry patient community for over 10 years, and we are extremely disappointed that we feel compelled to make this decision”.
Just last month, European regulators gave the green light to one of Shire’s US manufacturing facilities to produce the Gaucher disease treatment Vpriv (velaglucerase alfa) which was described as “a critical first step in releasing further capacity” for the manufacturing of Replagal at another US facility. However, earlier this month, Genzyme (now owned by Sanofi) began US deliveries of Fabrazyme from a newly-approved plant in Framingham, Massachusetts and expects a return to normal supply levels soon.
