The FDA has granted priority review status to Roche’s hemophilia A candidate emicizumab, setting up the Swiss drugmaker to learn its fate by Feb. 23. Roche enters the review process armed with impressive efficacy data that risks being undermined by safety concerns and a spat with Shire.
Genentech, Roche’s U.S. group, secured the priority review nod on the back of the breakthrough therapy designation it picked up from the FDA in 2015. Since then, clinical trial data have clarified the potential of emicizumab to treat hemophilia A patients that develop inhibitors to factor VIII—and dialed up the risk that safety problems will stop Roche from realizing its blockbuster dreams.
Boarding the regulatory review fast track means Roche will only have to wait 6 months, rather than the usual 10, to learn what the FDA makes of the risk-benefit profile of its bispecific antibody.
The data set presented to the FDA links emicizumab to an 87% drop in the bleed rate of patients with FVIII inhibitors. That positive headline finding is mitigated somewhat by the big differences in outcomes between responders and non-responders—although two-thirds of patients experienced no bleeds, the rest suffered about eight a year—and potentially more ruinously by safety data.
A small number of patients taking emicizumab suffered thromboembolic events or developed thrombotic microangiopathy (TMA) during the clinical development program. One patient died after suffering a serious rectal hemorrhage followed by TMA.
The investigator analyzing the patient death concluded emicizumab was blameless. For its part, Roche has consistently framed the blood clotting adverse events as a result of high, repeated doses of the on-demand bypassing agents Feiba and NovoSeven.
Shire, the manufacturer of Feiba, reacted badly to being fingered as the cause of the adverse events and responded by obtaining a preliminary injunction to stop Roche spreading what it sees as “inaccurate and misleading” statements.
The dispute is part of a wider tussle for the hemophilia market, which Roche is trying to muscle in on. Shire made a big bet on hemophilia by acquiring Baxalta. The returns it squeezes out of that investment will depend, in part, on the label emicizumab gets and, by extension, how quickly it starts realizing its blockbuster sales projections.