Sanofi and Regeneron’s investigational drug alirocumab is more effective at reducing cholesterol levels than Merck & Co’s Zetia in patients who are intolerant to statins, according to a new study.
The ODYSSEY ALTERNATIVE trial – reported at the American Heart Association (AHA) meeting in Chicago this week – suggests the PCSK9 inhibitor could be an alternative to Zetia (ezetimibe), which is commonly used in this hard-to-treat patient population.
Lead investigator Patrick Moriarty of the University of Kansas Medical Centre told the AHA that alirocumab was very effective at reducing LDL-cholesterol in this patient group, cutting it by 45% while Zetia managed only a 15% reduction over the 24-week trial.
“Statin intolerance is one of the most common causes of an inability to reach goals in patients who need lipid lowering therapy,” said Moriarty, adding that intolerance affects up to 25% of all statin-treated patients.
The trial compared alirocumab given by injection every two weeks to a daily dose of Zetia as well as a 20mg atorvastatin group to see whether patients deemed to be statin-intolerant could benefit from a low dose of the drug.
Patients had very high LDL-cholesterol levels at enrolment of around 190mg/dL. Moriarty said patients were motivated to reduce their cardiovascular risk and so were happy to put up with injectable versus oral therapy.
Interestingly, 75% of those labelled as statin-intolerant could actually tolerate the low dose of atorvastatin over the 24-week study period, which could raise question about the size of the patient population targeted by statin alternatives.
Alirocumab was also well tolerated with fewer side effects than the atorvastatin arm, although trial discussant Karol Watson of UCLA noted that discontinuation rates due to skeletal side effects were actually similar between the two groups.
Other unknowns in the trial included whether alirocumab will prove safe in longer-term studies, said Watson.
On the latter point, rival PCSK9 inhibitor developer Amgen reported pooled results from phase II and III studies suggesting that its evolocumab candidate maintained efficacy and safety over 52 weeks.
Evolocumab was shown to be equally effective when given every two or four weeks, according to Amgen, and also significantly reduced not only LDL-cholesterol but also lipoprotein a (LpA), thought to be a positive risk factor for cardiovascular disease.
Cardiologists are now waiting to see whether the impressive effects of the PCSK9 inhibitors on LDL-cholesterol and other surrogate markers will be backed up in outcome studies, particularly as the results of the IMPROVE-IT trial have now shown the benefit of boosting LDL-cholesterol reductions by adding Zetia to statins.
“There is a clear need for a large-scale, longer duration trials with hard cardiovascular outcomes,” commented Watson.
Amgen and Sanofi/Regeneron are in a head-to-head race to bring the first PCSK9 inhibitor to market as a treatment for elevated cholesterol, with Amgen now in the lead after it filed for approval of evolocumab a few weeks ago in the US.
Sanofi and Regeneron have not yet filed for approval of their alirocumab candidate but closed the gap on Amgen after paying $67.5m to buy a priority review voucher awarded to BioMarin by the FDA.
Amgen has also filed a lawsuit accusing Sanofi and Regeneron of infringing its patents on PCSK9 inhibition.