Pfizer has suspended the global development of its pipeline proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, bococizumab, due to a lack of predicted value.
Pfizer has suspended the global development of bococizumab due to issues with the drug’s clinical profile and the currently challenging market landscape for PCSK9 inhibitors (Pfizer press release, 2016). While bococizumab’s discontinuation has delayed competition for Praluent (alirocumab; Sanofi/Regeneron) and Repatha (evolocumab; Amgen/Astellas), they still face a potential threat from PCSK9si (ALN-PCSsc; The Medicines Company/Alnylam), a first-in-class RNA interference therapeutic in Phase II trials.
The decision to discontinue the development of bococizumab was based on a number of clinical issues which emerged during the drug’s Phase III trial program. Bococizumab was found to cause higher levels of immunogenicity and injection site reactions in comparison to Praluent and Repatha, contraindicating its use as a long-term effective treatment (Pfizer press release, 2016). The cause of these clinical issues is currently unknown, but could be due to the fact that bococizumab is a humanized monoclonal antibody as opposed to a fully human candidate like its marketed competitors. Furthermore, bococizumab treatment was shown to cause an attenuation of low-density lipoprotein-cholesterol lowering over a 52-week period, which Pfizer postulated could be due to the presence of anti-drug antibodies (Pfizer press release, 2016; Scrip, 2016).
The challenging market landscape for PCSK9 inhibitors is likely to have played a part in Pfizer’s decision to discontinue the development of bococizumab. Pfizer’s offering would have been the third PCSK9 inhibitor to enter the dyslipidemia market, and current products have failed to live up to sales expectations (Biomedtracker, 2016). At around $14,000 per patient per year, and without the availability of outcomes data, physicians and decision makers have been reluctant to prescribe the costly PCSK9 inhibitors outside of very high-risk patient populations. The relatively small market for current PCSK9 inhibitors, along with bococizumab’s expected inferior clinical profile and third-to-market status, would likely have impacted Pfizer’s decision to discontinue the development of the drug.
While bococizumab’s discontinuation has delayed competition for Praluent and Repatha in the PCSK9 inhibitor space, the drugs will still face competition at a later date from The Medicines Company’s PCSK9si. Following bococizumab’s discontinuation, the Phase II PCSK9 synthesis inhibitor, PCSK9si, is expected to be the next drug to enter the PCSK9 inhibitor market. This therapy could seriously threaten Praluent and Repatha in the dyslipidemia space due to its proposed twice yearly dosing schedule. However, the drug will still have to overcome the same market and clinical challenges that bococizumab faced in order to gain approval and uptake for dyslipidemia.