PCSK9

Alirocumab versus Usual Care in Diabetes with Mixed Dyslipidemia – ODYSSEY DM-

DYSLIPIDEMIA Study

Robert R. Henry, MD University of California San Diego School of Medicine, and Center for Metabolic Research, Veterans Affairs, San Diego Healthcare System,

San Diego, California, USA

On behalf of the ODYSSEY DM Steering Committee

Lawrence A Leiter (Chair; Toronto, Canada), Bertrand Cariou (Nantes, France); Helen M Colhoun (Edinburgh, Scotland, UK), Dirk Müller-Wieland (Aachen, Germany), Robert R Henry (San Diego,

CA, USA), Kausik K Ray (London, UK), Stefano Del Prato (Pisa, Italy), Francisco J Tinahones(Malaga, Spain)

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PAGE TITLEDisclosures

• Dr. Robert H. Henry– Research funding from AstaMed, Eli Lilly and

Company, Hitachi, Lexicon, Novo Nordisk, and Viacyte;

– Consultant for and/or advisory panel member of Alere, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Elcelyx, Intarcia, Ionis, Janssen/Johnson & Johnson, Merck and Sanofi-Aventis

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PAGE TITLEPurpose / Objective: ODYSSEY DM-insulin study• CV a significant cause of morbidity and mortality in persons with

T2DM. Mixed dyslipidemia is commonly present in these patients and further increases their cardiovascular risk.

• Management of mixed dyslipidemia is a persistent challenge in clinical practice

• Objective: to show superiority of alirocumab versus usual care in individuals with T2 diabetes with “bad” lipid profile (mixed dyslipidemia) that is not adequately controlled with the maximum tolerated statin therapy

4CV : cardiovascular,

PAGE TITLEMethods• Open Label, RCT (2:1, alirocumab, usual care)

– open label period 24 weeks, safety follow up period 8 weeks

• Population: T2DM, with ASCVD/other additional CV risk factor(s), non-HDL ≥ 100 mg/dL, TG (≥150 - <500 mg/dL), not adequately controlled by MTD statins– 413 T2DM (276 received alirocumab, 137 received usual care)

• Primary endpoint : – % change (baseline to Week 24 in non-HDL-C)– Non-HDL-C : better predictor of CV risk than LDL-C, in

individuals with DM patients and mixed dyslipidemia)

5RCT : randomized clinical trial, ASCVD : atherosclerotic cardiovascular disease, MTD: maximum tolerated dose

PAGE TITLEPrimary efficacy endpoint : Alirocumab is superior to usual care in % of change from baseline to W24, non-HDL-C

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Alirocumab improved other lipid parameters vs usual care

Secondary efficacy endpoints

Primary efficacy endpoints

PAGE TITLEMajority of patients reaching non-HDL-C <100 and LDL <70 mg/dLwith alirocumab 75 mg and Alirocumab is safe vs usual care

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Alirocumab did not affect glucose control

Safety endpoint

Similar incidence of adverse events between alirocumaband usual care

Secondary efficacy endpoints

DM endpoints: absolute change A1c, FPG

PAGE TITLEKey Takeaways • First dedicated study: PCSK9i in individuals at high CV risk with T2DM and

mixed dyslipidemia, Head to Head study (alirocumab vs lipid-lowering usual care)

• Alirocumab;– Superior versus usual care in reducing non-HDL-C after 24 weeks– improved many other lipid parameters better vs usual care – Majority reaching non-HDL<100 , LDL < 70 mg/dL with alirocumab 75 mg– Non-HDL-C : better predictor of CV risk than LDL-C, in DM +mixed

dyslipidemia– Generally safe and well tolerated, did not affect diabetes endpoints

• Findings from ODYSSEY-DYSLIPIDEMIA will inform clinical decision-making beyond MTD statins answering important clinical question

• Next steps: additional results to be presented at future congresses (i.e : efficacy of alirocumab vs fenofibrates, detailed analysis of secondary endpoints to better understand effect of alirocumab on atherogenic mixed dyslipidemia and its mechanism of action)

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