Pfizer Ends Development Of Its PCSK9 Inhibitor

–Immune issues and diminishing efficacy doomed the new drug.

Pfizer announced on Tuesday that it was discontinuing development of bococizumab, its cholesterol-lowering PCSK9 inhibitor under development.

“The totality of clinical information now available for bococizumab, taken together with the evolving treatment and market landscape for lipid-lowering agents, indicates that bococizumab is not likely to provide value to patients, physicians, or shareholders,” the company explained.

Pfizer said that it would halt two very large ongoing cardiovascular outcome studies with bococizumab, the 17,000 patient SPIRE 1 trial and the 10,000 patient SPIRE 2 trial. The trials were fully enrolled.

Pfizer told me that the decision to discontinue development “was not based on a recommendation by the independent Data Monitoring Committee DMC)   to stop the program.”

Online speculation about the reasons for Pfizer’s withdrawal focused on the weak sales of the first generation of PCSK9 inhibitors from Amgen (Repatha, evolocumab) and Sanofi/Regeneron (Praluent, alirocumab). But the Pfizer announcement suggests reasons more specific to the individual drug, including immune reactions and lessening efficacy over time.

“With the completion of six bococizumab lipid-lowering studies” the company said it had “observed an emerging clinical profile that includes an unanticipated attenuation of low-density lipoprotein cholesterol (LDL-C) lowering over time.” This attenuation of effect has not been much discussed previously, since the results of the lipid-lowering trials have not yet been presented or published, though the company has stated that all the trials reached their primary endpoint. Approximately 4,000 patients were randomized in the lipid-lowering trials.

The company also cited “a higher level of immunogenicity and higher rate of injection-site reactions with bococizumab than shown with the other agents in this class.” One source speculated that this may reflect the fact that the Pfizer antibody was a humanized antibody and not a fully human antibody like the existing drugs on the market.

It seems then fair to assume that Pfizer chose to discontinue bococizumab because it would have been third to market with a problematic drug, though the weak market for the current drugs likely provided strong headwinds.

Paul Ridker (Brigham & Women’s Hospital) was the Co-chair of the Executive Committee The press release included a statement from Ridker, who vowed to present the available data from the trials: “To honor the altruism of trial participants, and to maximize the clinical and scientific knowledge derived from the halted trials, Pfizer has committed to ensuring that the data will be made available to study leaders for independent analysis and prompt public presentation. We believe the available data will allow us to test the core scientific questions posed by the overall program which is in the best interest of patients who volunteered in these clinical trials, and for patients worldwide who suffer from heart disease.”

Ridker told me that he had “nothing to add that isn’t in the press release; we are working to pull the core data together as quickly as possible.” Pfizer said that there had been no interim analyses by the DMC of the CVOTs.