Subcutaneous Cinryze: Phase IIb discontinued

ViroPharma discontinued a double-blind, crossover, international Phase IIb trial evaluating subcutaneous Cinryze in combination with Halozyme's recombinant human PH20 hyaluronidase ( rHuPH20) due to "an unexpected incidence and titer of non-neutralizing anti-rHuPH20 antibodies." ViroPharma said the antibodies have not been associated with any adverse clinical effects and are of unknown clinical significance. The trial, which completed enrollment of 41 adolescent and adult patients, was evaluating 1,000 units subcutaneous Cinryze plus 24,000 units rHuPH20 twice weekly and 2,000 units Cinryze plus 48,000 units rHuPH20 twice weekly. ViroPharma said all patients completed >=1 dosing arm and 20 completed both dosing arms. ViroPharma said it has developed a low-volume subcutaneous formulation of Cinryze and expects to conduct a Phase III trial next year with the alternative formulation within the same time frame previously anticipated for the rHuPH20 combination product.

In September, FDA lifted a clinical hold for subcutaneous Cinryze in combination rHuPH20 for HAE. FDA placed the clinical hold after raising concerns in a complete response letter for a BLA for subcutaneous HyQ from Halozyme's partner Baxter International Inc. (NYSE:BAX, Deerfield, Ill.) to treat primary immunodeficiency disorder (PID). FDA had concerns about non-neutralizing antibodies generated against rHuPH20, which is a component in HyQ along with IV Gammagard, an IgG antibodies plasma-based therapy (see BioCentury, Aug. 6, 2012 & Sept. 24, 2012). ViroPharma restarted the trial in December. Halozyme said the discontinuation does not affect Baxter's plan to resubmit the BLA for HyQ, now known as HyQvia in the U.S., by the end of the year. The company also said 9 trials in 8 programs for subcutaneous rHuPH20 have been completed with no antibody findings other than those for Cinryze and HyQ. ...