Pfizer will stop developing its cholesterol-lowering drug bococizumab, an antibody against proprotein convertase subtilisin kexin type 9 (PCSK9). The New York–based big pharma made the surprise announcement November 1, citing “an emerging clinical profile that includes an unanticipated attenuation of low-density lipoprotein cholesterol (LDL-C) lowering over time.” Pfizer also mentioned higher rates of immunogenicity and injection-site reactions with bococizumab than with the two anti-PCSK9 antibodies: Praluent (alirocumab), co-developed by Regeneron Pharmaceuticals of Tarrytown, New York, and Paris-based Sanofi, and Thousand Oaks, California–based Amgen's Repatha (evolocumab) (Nat. Biotechnol. 33, 785, 2015), both approved in 2015. Unlike the fully human Praluent and Repatha, bococizumab is a humanized antibody.
Pfizer was testing the drug's ability to lower lipid in six phase 3 studies and to reduce cardiovascular outcomes such as heart attack and stroke in two other large studies. Several observations suggest its inability to maintain long-term and durable cholesterol lowering is specific to the product and not a class effect. For example, injection site reactions, which were seen at a higher rate than in the placebo group in both phase 2 and phase 3 trials, may have contributed to a higher rate of treatment failures in phase 3 given the longer exposure in those trials, Leerink Swann analyst Geoffrey Porges said in a note to investors. “From a commercial standpoint, if these local reactions persisted or increased in the longer duration and expanded recruitment of the phase 3 trials, then this alone could have compromised the drug's commercial potential,” he said. In earlier trials, bococizumab was also associated with relatively high anti-drug antibodies, which had no impact on drug effectiveness during the six months when they were measured, but could have cast doubt on the drug's effectiveness in the longer term.
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