Maja Bujas-Bobanovic

Efficacy and safety of alirocumab in insulin‐treated individuals with type 1 or type 2 diabetes and high cardiovascular risk: The ODYSSEY DM‐INSULIN randomized trial

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Lipid-Lowering Efficacy and Safety of Alirocumab in Patients with or without Diabetes: A Sub-Analysis of ODYSSEY COMBO II.

This sub‐analysis of the ODYSSEY COMBO II study compared the effects of alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, in high cardiovascular risk patients with or without diabetes mellitus (DM) receiving maximally tolerated statin therapy.

Alirocumab versus usual lipid-lowering care as add-on to statin therapy in individuals with type 2 diabetes and mixed dyslipidaemia: The ODYSSEY DM-DYSLIPIDEMIA randomized trial

To compare alirocumab, a proprotein convertase subtilisin‐kexin type 9 inhibitor, with usual care (UC) in individuals with type 2 diabetes (T2DM) and mixed dyslipidaemia not optimally managed by maximally tolerated statins in the ODYSSEY DM‐DYSLIPIDEMIA trial (NCT02642159).

Patient and Physician Perspectives on Mode of Administration of the PCSK9 Monoclonal Antibody Alirocumab, an Injectable Medication to Lower LDL-C Levels

PURPOSE Clinical trials of the PCSK9 inhibitor alirocumab, an every 2 week injectable monoclonal antibody, have shown significant reductions in LDL-cholesterol. However, many patients requiring lipid-lowering therapy are not experienced with self-injected medication. This study assessed patient and physician perceptions of 2 alirocumab delivery devices. METHODS 400 participants (200 physicians, 200 patients) were included from 6 countries. Physicians (99 primary care physicians [PCPs]; 101 specialists) had mean practice experience of 17.8 years and an average of 797 hypercholesterolemic patients. Participating patients had LDL-C levels above their goal and at least one of the following: familial hypercholesterolemia, statin intolerance, high cardiovascular risk, and/or diabetes. Mean patient age was 58.5 years, 51% were female, and 25.5% had injectable medication experience. Following device instruction and demonstration, participants tested either a pre-filled pen or pre-filled syringe, using both 75 and 150 mg doses of single-blinded placebo into a prosthetic pad. Data were collected by self-administered questionnaire. FINDINGS Participant acceptance of both devices was positive, with 83-100% agreeing with ease-of-use statements. After testing, physicians estimated that 66% (pen) and 58% (syringe) of their patients would be willing to self-inject using the device (relative increases from pre-testing of 22% and 16%, respectively; both P<0.05). Specialist estimates were higher than PCP estimates: for the pen, 60% versus 47% (pre-testing), respectively, and 72% versus 61% (post-testing); for the syringe, 57% versus 43% (pre-testing), 63% versus 54% (post-testing; all P<0.05, specialist vs PCP). After testing, 72% (pen) and 63% (syringe) of patient-participants were very willing to self-inject (relative increases from pre-testing of 26% [P<0.05] and 11%, respectively); 96% (pen) and 93% (syringe) were either very willing or somewhat willing to self-inject. The proportion of patients aged <60 years who were very willing to self-inject with either device was numerically (but not statistically) higher compared with those ≥60 years. Initially, patients with injectable medication experience were generally more willing to use the pen than injection-naive patients; after testing there was no difference between groups. No significant differences were observed in responses to the 2 different doses. IMPLICATIONS Responses from physicians and patients to pre-filled pen and syringe devices were positive. Devices were considered easy to operate, with most patients willing to use and accept self-injection. Patient willingness to self-inject increased after demonstration and testing. Results suggest that, in clinical practice, alirocumab administration by either pre-filled pen or syringe would not deter most physicians from prescribing or most patients from self-administering.

Efficacy and safety of alirocumab in insulin-treated patients with type 1 or type 2 diabetes and high cardiovascular risk: Rationale and design of the ODYSSEY DM–INSULIN trial

AIMS The coadministration of alirocumab, a PCSK9 inhibitor for treatment of hypercholesterolaemia, and insulin in diabetes mellitus (DM) requires further study. Described here is the rationale behind a phase-IIIb study designed to characterize the efficacy and safety of alirocumab in insulin-treated patients with type 1 (T1) or type 2 (T2) DM with hypercholesterolaemia and high cardiovascular (CV) risk. METHODS ODYSSEY DM-INSULIN (NCT02585778) is a randomized, double-blind, placebo-controlled, multicentre study that planned to enrol around 400 T2 and up to 100 T1 insulin-treated DM patients. Participants had low-density lipoprotein cholesterol (LDL-C) levels at screening≥70mg/dL (1.81mmol/L) with stable maximum tolerated statin therapy or were statin-intolerant, and taking (or not) other lipid-lowering therapy; they also had established CV disease or at least one additional CV risk factor. Eligible patients were randomized 2:1 to 24weeks of alirocumab 75mg every 2weeks (Q2W) or a placebo. Alirocumab-treated patients with LDL-C≥70mg/dL at week 8 underwent a blinded dose increase to 150mg Q2W at week 12. Primary endpoints were the difference between treatment arms in percentage change of calculated LDL-C from baseline to week 24, and alirocumab safety. RESULTS This is an ongoing clinical trial, with 76 T1 and 441 T2 DM patients enrolled; results are expected in mid-2017. CONCLUSION The ODYSSEY DM-INSULIN study will provide information on the efficacy and safety of alirocumab in insulin-treated individuals with T1 or T2 DM who are at high CV risk and have hypercholesterolaemia not adequately controlled by the maximum tolerated statin therapy.

Effect of alirocumab on lipids and lipoproteins in individuals with metabolic syndrome without diabetes: Pooled data from 10 phase 3 trials

This analysis assessed the efficacy and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, in patients with or without metabolic syndrome (MetS) using pooled data from 10 phase 3 ODYSSEY trials.

Efficacy and safety of alirocumab among individuals with diabetes mellitus and atherosclerotic cardiovascular disease in the ODYSSEY phase 3 trials

Individuals with both diabetes mellitus (DM) and atherosclerotic cardiovascular disease (ASCVD) are at very high risk of cardiovascular events. This post‐hoc analysis evaluated efficacy and safety of the PCSK9 inhibitor alirocumab among 984 individuals with DM and ASCVD pooled from 9 ODYSSEY Phase 3 trials.