Pfizer has announced that it is no longer developing bococizumab, a PCSK9 inhibitor; the drug had been in Phase III for treating hypercholesterolemia. In Pfizer’s press release, the company reported that “an emerging clinical profile that includes an unanticipated attenuation of low-density lipoprotein cholesterol (LDL-C) lowering over time, as well as a higher level of immunogenicity and higher rate of injection-site reactions with bococizumab than shown with the other agents in this class.” Consequently, Pfizer believes that “bococizumab is not likely to provide value to patients, physicians, or shareholders.” It would seem that it was only in the large cardiovascular outcomes trial that these findings have come to light. This will come as a major blow to Pfizer, especially as thought leaders had considered bococizumab essentially equivalent to the PCSK9 inhibitors on the market: Amgen’s Repatha (evolocumab) and Sanofi/Regeneron Pharmaceuticals’ Praluent (alirocumab). However, the administration reactions, reduced treatment effect, and concerns over antibody production, would have made it difficult for bococizumab to gain traction against its established rivals.
This is the first major setback for the novel PCSK9 inhibitor class, which is currently considered a major advance in the treatment of hypercholesterolemia, and these drugs were all expected to deliver significant reductions in the risk of CV events. Now, regulatory authorities will be even more interested in the data that will come with completion of the cardiovascular outcomes trials for Repatha and Praluent, which are first expected in Q1 2017 and Q1 2018, respectively. The good news for patients, physicians, and the developers of the currently available PCSK9 inhibitors is that the reasons behind the discontinuation appear to be drug- rather than class-specific; with more patient-years already racked up for Repatha and Praluent than for bococizumab, it is unlikely the former drugs will demonstrate the same issues that have arisen with the latter. There could even be a silver lining for Amgen and Sanofi/Regeneron as Repatha and Praluent will face no further competition for a longer time. With Eli Lilly’s LY-3015014 seemingly stalled in Phase II development, we are now looking to The Medicines Company’s PCSK9si drug. This drug has demonstrated positive Phase II data from the ORION-1 trial and has the potential for biannual administration, according to an October 18 press release, adding to its appeal, but it is still years from the market.
As a result, it might be that two other drugs may also benefit from the demise of bococizumab: Esperion Therapeutic’s bempedoic acid (ETC-1002), which is being developed as a monotherapy and in combination with ezetimibe (Merck’s Zetia/Ezetrol), and Merck’s anacetrapib, the most advanced of the much maligned CETP inhibitor class. Both agents are once-daily, orally administered therapies that lower LDL-cholesterol and this could appeal to patients and physicians, and see them fill the potential void left by bococizumab before The Medicines Company’s drug enters the market. At this stage, it appears that the broad dynamics of the dyslipidemia market will not be substantially affected; although one promising agent has fallen at the final hurdle, new and emerging therapies will leap at the chance to fill the void.