CADTH CANADIAN DRUG EXPERT COMMITTEE FINAL RECOMMENDATION: Common Drug Review CDEC Meeting — June 15, 2016  Notice of Final Recommendation — July 20, 2016

Alirocumab
(Praluent – Sanofi-aventis Canada Inc.) Indication: Primary Hyperlipidemia

For Heterozygous Familial Hypercholesterolemia

Recommendation:
The Canadian Drug Expert Committee (CDEC) recommends that alirocumab be reimbursed as an adjunct to diet and maximally tolerated statin therapy in adult patients with heterozygous familial hypercholesterolemia (HeFH), who require additional lowering of low density lipoprotein cholesterol (LDL-C), if the following clinical criteria and condition are met.

Criteria:

1. Patient has a confirmed diagnosis of HeFH
2. Patient is unable to reach the target LDL-C level specified in current guidelines
3. Patient is currently receiving optimally tolerated standard of care (maximally tolerated statins(MTS) with or without ezetimibe)

Condition:

1. Reduced price

Reasons for the Recommendation:

1. Three double-blind randomized controlled trials (RCTs) of HeFH patients who had elevated LDL-C levels despite receiving optimized standard of care (FH1, FH2, and HIGH FH) and one mixed-population study of patients at high risk for CV events and/or who had elevated LDL-C levels (ODYSSEY LONG TERM) demonstrated that alirocumab(75 mg or 150 mg every two weeks) was statistically significantly superior to placebo for lowering LDL-C levels. In addition, a statistically significantly greater proportion of patients was able to achieve a prespecified LDL-C target level compared to placebo-treated patients.
2. CDEC considered alirocumab not to be cost effective at the submitted price of $279.36 per 75 mg/mL or 150 mg/mL pre-filled syringe. At this price a re-analyses of the manufacturer’s pharmacoeconomic model suggested that for a mixed population with elevated LDL-C levels that comprised HeFH patients and high-risk of CV events patients, alirocumab + MTS was associated with an incremental cost-utility ratio (ICUR) of $126,375 per quality-adjusted life year (QALY) when compared to MTS alone.For a population of HeFH patients with elevated LDL-C levels only, the ICUR was $143,401 per QALY.

For Clinical Atherosclerotic Cardiovascular Disease
Recommendation:
CDEC recommends that alirocumab be reimbursed as an adjunct to diet and maximally tolerated statin therapy in adult patients at high risk for cardiovascular (CV) events, who require additional lowering of LDL-C, if the following clinical criteria and condition are met.

Criteria:

1. Patient is unable to reach the target LDL-C level specified in current guidelines
2. Patient is currently receiving optimally tolerated standard of care (MTS with or withoutezetimibe)

Condition:

1. Reduced price

Reasons for the Recommendation:

1. Two double-blind RCTs of patients at high risk for CV events (COMBO1 and COMBO2) and one mixed-population study of patients at high risk for CV events and/or who had elevated LDL-C levels (ODYSSEY LONG TERM) demonstrated that alirocumab (75 mg or 150 mg every two weeks) was statistically significantly superior to placebo for lowering LDL-C levels. In addition, a statistically significantly greater proportion of patients was able to achieve a prespecified LDL-C target level compared to placebo-treated patients.
2. CDEC considered alirocumab not to be cost effective at the submitted price of $279.36 per 75 mg/mL or 150 mg/mL pre-filled syringe. At this price, a re-analyses of the manufacturer’s pharmacoeconomic model suggested that for a mixed population with elevated LDL-C levels that comprised HeFH patients and high-risk of CV event patients, alirocumab + MTS was associated with an ICUR of $126,375 per QALY when compared to MTS alone. For a population of patients with high-risk of CV events only, the ICUR was $124,664 per QALY.

Of Note:

1.Clinical trials of alirocumab were conducted using a target LDL-C level of 1.8 mml/L. Other trials of PCSK9 inhibitors have used other LDL-C targets. CDEC recommends that current published guidelines be consulted to determine the most appropriate LDL-C targets for individual clinical situations.

2.HeFH diagnosis should be confirmed by genotyping and/or using clinical criteria such as the Simon Broome criteria or World Health Organization/Dutch Lipid Network criteria.

3.CDEC noted that a price reduction of at least 57% would be required for alirocumab to be considered to be a cost-effective treatment option in a mixed population of HeFH patients and in patients with a high risk of CV events.

Background:

Alirocumab is a monoclonal antibody that binds and inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9). Alirocumab is approved by Health Canada as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with HeFH or clinical atherosclerotic cardiovascular disease (CVD) who require additional lowering of low density lipoprotein cholesterol (LDL-C). It is available as a subcutaneous injection. The recommended starting dose is 75 mg once every 2 weeks, which can be increased to 150 mg every two weeks if the LDL-C response is inadequate.

Full Recommendation Report on Alirocumab from CADTH

Common Drug Review CDEC Meeting — June 15, 2016  Notice of Final Recommendation — July 20, 2016 SR0469 © 2016 CADTH