ODYSSEY MONO results add to excitement surrounding the PCSK9 class, but CV outcomes data will be key.
By Victoria Hudson, Senior Analyst
18 October 2013
I am the senior analyst for Datamonitor Healthcare’s cardiovascular and metabolic team, and cover everything from acut...
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On 16 October 2013, Sanofi and Regeneron announced promising top-line data for alirocumab in the ODYSSEY MONO trial. These are the first Phase III top-line data announced for a proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor in dyslipidemia. The promising top-line Phase III results are expected to add to the excitement surrounding the PCSK9 inhibitor class as a whole. However, alirocumab’s potential within the indication will also depend on the results of Phase III trials that are investigating the drug as an add-on to statin therapy and its impact on cardiovascular (CV) outcomes.
Alirocumab’s promising top-line efficacy data in the ODYSSEY MONO trial are expected to add to the anticipation surrounding the PCSK9 inhibitor class as a whole. With monotherapy alirocumab demonstrating superior efficacy to Zetia (ezetimibe; Merck & Co), the PCSK9 inhibitor has the potential to become a leading alternative therapy for statin-intolerant patients. Alirocumab demonstrated a mean low-density lipoprotein cholesterol (LDL-C) reduction from baseline over 24 weeks of 47.2% versus 15.6% with Zetia. The majority of patients received a 75mg dose of the drug.
While the first Phase III results for alirocumab clearly demonstrate the therapy’s potential as a monotherapy antidyslipidemic, the greatest potential for the drug and the class as a whole lies in lowering LDL-C on top of statin therapy. This is because the majority of patients are treated with widely genericized statin therapy in dyslipidemia. Earlier Phase II results for alirocumab showed that 150mg of the drug in addition to the statin Lipitor (atorvastatin; Pfizer) led to an average reduction of 65% in LDL-C from baseline. Alirocumab is undertaking two Phase III trials, ODYSSEY COMBO 1 and 2, involving patients on statin therapy, which are due to complete in 2014.
Another key trial for alirocumab is the ODYSSEY Outcomes trial evaluating CV outcomes. If treatment with alirocumab is shown to result in a significant reduction in CV outcomes, then the drug will have a significant clinical advantage within dyslipidemia. This will be particularly important given the ever-expanding list of therapies that have failed to demonstrate a benefit in CV outcomes. This list includes Niaspan (nicotinic acid; Merck & Co) in the AIM-HIGH trial, Tredaptive (nicotinic acid and laropiprant; Merck & Co) in the HPS2-THRIVE trials, and Zetia in the ENHANCE trial.
A potential disadvantage of the ODYSSEY Outcomes trial is that it does not measure the baseline benefit achieved by statin therapy. The trial may have been designed this way because of the failure of previous trials that included baseline statin therapy, but this means that it will not show if adding alirocumab to statin therapy provides a CV outcomes benefit. This is important because Amgen’s PCSK9 inhibitor AMG 145 is in a Phase III CV outcomes trial, FOURIER, which includes baseline atorvastatin therapy. With Amgen’s AMG 145 so closely following alirocumab in Phase III clinical development, the results from both the ODYSSEY Outcomes and FOURIER trials will be crucial to differentiating the anticipated first and second-to-market PCSK9 inhibitors within dyslipidemia. Datamonitor Healthcare forecasts alirocumab to reach sales of $238m in 2018 and AMG 145 to reach sales of $271m in 2018.
Posted in Metabolic.