Shire is reporting positive results from two Phase III studies with its Gaucher’s disease drug candidate and that it has completed its NDA. Last month the FDA accepted the treatment protocol, allowing this enzyme replacement therapy, velaglucerase alfa, to be administered to certain patients under specific guidelines before final approval.
The decision to sanction the treatment protocol came after Shire revealed that its first Phase III trial had succeeded. In July the agency asked Shire and Protalix to submit treatment protocols for their respective Gaucher’s therapies in the wake of Genzyme’s approved drug being in short supply. In June Genzyme had to shutter one of its plants due to viral contamination, thus bringing the supply of Cerezyme, which was produced at that facility, under threat. Protalix’ treatment protocol has also been approved by the FDA.
Shire is on-track to submit a European filing for velaglucerase alfa by the end of 2009, says Sylvie Gregoire, president of Shire Human Genetic Therapies. The velaglucerase alfa program included over 100 patients at 24 sites in 10 countries.
Velaglucerase alfa is made using Shire's technology in a human cell line. The enzyme produced has the exact human amino acid sequence and has a human glycosylation pattern, according to Shire.
All three Phase III studies of velaglucerase alfa in type 1 Gaucher’s patients showed that it was generally well tolerated in both treatment-naïve and previously treated Gaucher’s patients. The three studies included: Study 032, which studied velaglucerase alfa in naïve patients; Study 039, which was a head-to-head study of velaglucerase alfa and Cerezyme; and Study 034, which was a switch study from imiglucerase to velaglucerase alfa.
As reported on August 3, Study 032 in naïve patients met its primary endpoint, which evaluated change in hemoglobin concentrations from baseline. Study 039 was a nine-month, randomized, double-blind efficacy study in 34 treatment-naïve patients aged two years and older.
The primary endpoint was the comparison of increases in hemoglobin concentrations between the velaglucerase alfa and imiglucerase groups. Secondary endpoints were comparisons of increases in platelet counts, decreases in organ volumes, and surrogate markers of Gaucher’s disease. Velaglucerase alfa demonstrated robust clinical efficacy that was comparable to imiglucerase in all endpoints, according to Shire.
Study 034 was a 12-month trial in 40 clinically stable patients aged two years and older who had been receiving treatment with imiglucerase at doses ranging between 15 U/kg and 60 U/kg every other week for a minimum of 30 consecutive months. In this evaluation, hemoglobin concentrations, platelet counts, and organ volumes were sustained through 12 months of velaglucerase alfa treatment and the therapy was generally well tolerated, Shire notes.