Jan. 9 Quick Takes: Arrowhead falls on unexpected high placebo response in AAT study

Arrowhead Pharmaceuticals Inc. (NASDAQ:ARWR) lost about $750 million in value on Monday after the biotech and its partner Takeda Pharmaceutical Co. Ltd. (Tokyo:4502; NYSE:TAK) reported top-line data from the Phase II SEQUOIA study of fazirsiran (TAK-999/ARO-AAT) for liver disease associated with alpha-1 antitrypsin deficiency (AATD-LD). While treatment of 16 AATD patients with the RNAi therapy showed an impressive median reduction of 94% of liver Z-AAT expression, there was an unexpectedly high number of placebo responders on the fibrosis endpoint. In the study, seven (50%) of 14 treated patients showed an improvement of fibrosis of at least one point by METAVIR stage, while 38% (3/8 patients) showed fibrosis improvement on placebo. The partners said Takeda plans to start a Phase III study this month of fazirsiran in 160 AAT patients. Shares of Arrowhead were off $7.10 (19%) to $30.28 on Monday. 

With three years of follow up from the Phase III GENEr8-1 study, factor VIII levels in severe hemophilia A patients who received in vivo gene therapy valoctocogene roxaparvovec from BioMarin Pharmaceuticals Inc. (NASDAQ:BMRN) remained above the threshold for moderate disease, but activity continued to decline over time. BioMarin reported that the gene therapy led to median FVIII activity of 8.4 IU/dL in year three in the 134-patient study, and 7.4 IU/dL among the 17 patients with four years of follow-up, off from 11.8 IU/dL at two years. Though annualized bleeding rates requiring treatment remained relatively consistent at a mean of 1.0, annualized FVIII utilization more than doubled to 8.4 from two to three years in the study. Valoctocogene roxaparvovec has a March 31 PDUFA date, but the company previously said the Phase III data report requested by FDA may represent a major amendment that pushes the date back by three months...