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Nov 12, 2012
 |  BioCentury  |  Product Development

Piecing together PCSK9

Cholesterol data from Amgen sheds light on race between anti-PCSK9 mAbs

Last week's Phase II data for anti-PCSK9 mAbs from Amgen Inc. and Pfizer Inc. revealed no surprises and kept intact the hypothesis that hitting the target is a new modality for lowering cholesterol with or without statin background therapy. The data do allow for a rough comparison between Amgen's molecule and the most advanced member of the class - twice monthly REGN727 from Regeneron Pharmaceuticals Inc. and Sanofi - and show no clear winner.

While Pfizer is keeping mum on how it hopes to differentiate its RN316 (PF-04950615) from the pack, Amgen thinks it could come down to dosing. Indeed, the biotech bellwether hopes to counter REGN727's six to nine month head start in the clinic by offering a monthly dosing option for AMG 145.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an enzyme that plays a role in cholesterol homeostasis by inducing degradation of the LDL receptors that would otherwise clear LDL-C from the bloodstream.

The first Phase II data for an anti-PCSK antibody were reported last year by Regeneron and Sanofi (see BioCentury, Nov. 21, 2011).

In three Phase II trials, twice-monthly subcutaneous REGN727 (SAR236553) significantly reduced LDL-C after 12 weeks in patients who had baseline levels of at least 100 mg/dL despite already being on lipid-lowering therapy. One trial (1003) enrolled patients with heterozygous familial hypercholesterolemia (heFH), while the other two (11565 and 11566) were in primary (non-familial) hypercholesterolemia.

At this month's American Heart Association meeting in Los Angeles, Amgen and Pfizer unveiled Phase II POC data for their mAbs. Amgen reported results from four studies while Pfizer announced findings from a Phase IIa trial.

The closest apples to apples comparison is between the RUTHERFORD study of AMG 145 and Study 1003 of REGN727.

In RUTHERFORD, 350 and 420 mg doses of AMG 145 given every four weeks each met the primary endpoint of reducing LDL-C from baseline to week 12 (43%...

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