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Safety Factor

How Pfizer aims to compete in the Factor XIa space

Although the advent of Factor Xa inhibitors improved quality of life for many thrombosis patients, the compounds' bleeding risk prevents use in patient populations with certain co-morbidities, and has prompted a handful of companies to explore Factor XI inhibition in parallel. Now, Pfizer Inc. is joining the hunt with a preclinical mAb that has efficacy in rabbits comparable to Bayer AG's Factor Xa inhibitor Xarelto rivaroxaban, with substantially less bleeding.

Despite the fact there are three products targeting Factor XI in clinical development, Pfizer thinks its mAb may provide an even greater safety benefit than the compounds it trails by selectively targeting the enzyme's active site, and because the company has already made a tailored reversal agent.

Factor Xa and Factor XIa are the activated forms of Factor X and Factor XI - proteases in the coagulation cascade that contribute to clot formation. But whereas Factor XI is part of the intrinsic pathway, which is activated inside the bloodstream to wall-off bacteria or other foreign substances, Factor X is on the common pathway downstream of both the intrinsic and extrinsic coagulation pathways, the latter being typically set off by a breach in blood vessel walls .

According to Thomas Mikita, senior principal scientist at Pfizer's San Francisco-based Center for Therapeutic Innovation (CTI), drug companies initially targeted proteins in the extrinsic or common pathways because of their clear requirement in hemostasis - the ability to retain blood following vessel injury.

"It was

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