Bococizumab – What does it mean for FH patients?

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What Does News of Pfizer’s Discontinuation of PCSK9 Inhibitor Program Mean for FH Patients?

With the news that Pfizer, Inc has discontinued development of its PCSK9 inhibitor, bococizumab, the FH Foundation reached out to our Chief Scientific Advisor, Dan Rader, MD, Seymour Gray Professor of Molecular Medicine at the Perelman School of Medicine, University of Pennsylvania to help us understand what this decision is about and what it says about the two PCSK9 inhibitors, Amgen’s evolocumab (Repatha) and Sanofi/Regeneron’s alirocumab (Praluent), already approved by the FDA and available to patients.

“Bococizimab is a “humanized” antibody whereas alirocumab and evolocumab are “fully human” antibodies. While these sound similar, the process of ‘humanization’ (in contrast to creating ‘fully human’ antibodies) leaves some residual mouse [genetic] sequence that can be immunogenic in some cases. Alirocumab and evolocumab both only contain fully human [genetic] sequences. This difference may have accounted for the increased immunogenicity, generation of anti-drug antibodies, site-reactions, and attenuation of LDL-lowering over time with bococizumab. This does not necessarily have implications for the “fully human” antibodies on the market, where these effects have not been seen.”

Dr. Dan Soffer, Clinical Associate Professor of Medicine, University of Pennsylvania, adds: “The available PCSK9 inhibitors were approved by the FDA based upon safety and LDLc-lowering effectiveness data, contingent upon completion of studies to address cardiovascular benefit (ongoing, stay tuned). Loss of efficacy over time has not been seen with the two approved drugs, evolocumab (Repatha) and alirocumab (Praluent) when observed for more than 18 months.”

The FH Foundation is committed to encouraging early diagnosis and proactive treatment for everyone with Familial Hypercholesterolemia so more families have the chance to prevent early heart disease. The road to finding safe and effective treatments is a long and hard one, with many disappointments along the way, as Pfizer’s decision reflects. Even after treatments have been approved, accessing those treatments can be challenging for patients – we need to find ways to address those challenges in the interest of optimizing FH care for those who are out of options and with no time to waste.

CASCADE FH™ Registry data show that many FH patients, even on statin therapy, still have LDL cholesterol levels that are too high, leaving them at increased risk for early heart disease. We are grateful for the FH treatment options we have – statins, ezetimibe, bile acid sequestrants, niacin, PCSK9 inhibitors, LDL apheresis, and lomitapide, and mipomersen for Homozygous FH – and for potential new treatments in development. Most of all, we are grateful to all of the patients who have participated in clinical trials to help make safe and effective options possible for fellow patients and their families.

Thank you.

Link to Pfizer’s statement:
http://www.pfizer.com/news/press-release/press-release-detail/pfizer_discontinues_global_development_of_bococizumab_its_investigational_pcsk9_inhibitor

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