Have you ever had that holiday experience, when you thought you were going to receive an amazing gift, but when the big day arrived you got socks? Practical and nice to receive anything of course, but not what you were hoping for. Similarly, for the dyslipidemia drug market, 2016 didn’t deliver quite what many expected. The PCSK9 inhibitors did not take off (and one crashed), the ‘good cholesterol’ might not be quite so good as was thought, and significant outcomes data does not impress everyone.
The PCSK9 inhibitors were supposed to take the market by storm according to some analysts, but as the DRG team suspected, the lack of cardiovascular outcomes data and the extremely high cost of these injectable drugs resulted in limited prescribing and plenty of restrictions from payers and regulators in the major markets. There is no doubting the LDL-cholesterol efficacy of Amgen’s Repatha and Sanofi/Regeneron’s Praluent but until reduction in mortality and morbidity are demonstrated, use of these agents will be limited. In another blow to the class, Pfizer’s PCSK9 inhibitor candidate was discontinued as the company felt that the data thus far suggested it would not match its rivals already on the market.
LDL-cholesterol is the ‘bad’ cholesterol with a huge amount of evidence linking high levels to CV risk and similar amounts of evidence showing that reducing LDL-cholesterol reduces CV risk. On the other hand was HDL-cholesterol, the ‘good cholesterol’. Epidemiology studies had shown that low levels were associated with increased CV risk. The supporters of the HDL hypothesis had placed high hopes on CETP inhibitors which could dramatically increase HDL-cholesterol as well as moderately decrease LDL-cholesterol suggesting a potentially powerful approach for treating dyslipidemia. However, 2016 saw the presentation of data from Eli Lilly’s evacetrapib negative CV outcomes trial – evacetrapib was the third drug in the class to fail – plus an observational study demonstrating a U-curve for HDL-cholesterol levels and all-cause mortality in patients with kidney disease.
Even positive outcomes data may not be persuasive. In late 2014, the first solid evidence of CV benefit from Merck’s Zetia/Vytorin emerged as the results of the IMPROVE-IT trial were presented at the AHA meeting. It was widely expected that this would lead to a label expansion highlighting this benefit. The EMA agreed, but in February 2016 Merck announced that the company had received a complete response letter from the FDA regarding the company’s application for wider use. With patent expiry looming for Zetia, any pre-generic competition bonus for the company in the lucrative U.S. market seems to be slipping away.
All in all, the dyslipidemia market provided no major surprises: the statins continue to dominate management and there is limited evidence that other drugs really help. Let’s hope that in 2017, new drugs can deliver meaningful CV benefits – yes, I’m looking at you Repatha and Praluent.