Rankings / Metabolic Health

PCSK9 inhibitors (evolocumab / alirocumab / inclisiran)

Metabolic Health · Monoclonal antibody or siRNA

Tier S

Reviewed by Read Off Label · Last reviewed · How we grade

statinpcsk9rna-therapymonoclonal-antibodyprescription
8.7 / 10
Tier S
Ev 8 Bn 10 Sf 9

Bottom line

Read Off Label grades PCSK9 inhibitors (evolocumab / alirocumab / inclisiran) as S (8.7/10) based on strong evidence, very strong benefit magnitude, and a low-risk safety profile.

Reserved historically for familial hypercholesterolemia, statin intolerance, or high-risk secondary prevention with inadequate LDL on maximal statin.

Studied, labeled, or reported-use context: Evolocumab 140 mg subQ q2wk or 420 mg monthly; alirocumab 75-150 mg subQ q2wk; inclisiran 284 mg subQ… — Rx (expensive at list; list prices now lower — ~$500-600/month after 2018 price cuts); enlicitide (Lipfendra) adds an oral option, FDA-approved July 2026; not individualized guidance.

Citation correction in progress

1 PubMed link was found to be unrelated to this entry and removed from public output. The remaining sources are shown below, but this row's claims and score still need a full source-by-source revalidation.

What the evidence says

Reserved historically for familial hypercholesterolemia, statin intolerance, or high-risk secondary prevention with inadequate LDL on maximal statin. Cost has dropped substantially but remains high. Inclisiran's 2x/year dosing is attractive for adherence. Lerodalcibep (Lerochol), a small monthly anti-PCSK9 recombinant protein, has reached approval as a newer option in the class. The FDA approved Lipfendra (enlicitide decanoate) on July 16, 2026 as the first oral once-daily PCSK9 inhibitor, a 20 mg macrocyclic-peptide tablet. Phase 3 CORALreef Lipids/HeFH showed 55-60% LDL-C reductions, comparable to the injectable antibodies; the CORALreef AddOn head-to-head trial (JACC 2026) found enlicitide superior to bempedoic acid, ezetimibe, and the combination on LDL-C (-64.6% vs -6.3% / -27.8% / -36.5% at day 56, all p<0.001). Oral dosing removes the injection barrier that limited uptake of this class; cardiovascular-outcomes data are still pending.

Mechanism

Block PCSK9 (which degrades LDL receptors) — resulting LDL receptor recycling drives circulating LDL-C down 50-60% on top of statin; inclisiran is siRNA silencing PCSK9 mRNA, dosed every 6 months

Studied, labeled, or reported dose & route

Evolocumab 140 mg subQ q2wk or 420 mg monthly; alirocumab 75-150 mg subQ q2wk; inclisiran 284 mg subQ at 0, 3 mo, then every 6 mo; enlicitide (Lipfendra) 20 mg PO once daily

This records doses and routes described in studies, approved labeling, clinical practice, or documented use. It is not individualized guidance and does not establish safety; context changes with indication, formulation, health history, monitoring, and other medicines.

Citations

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Common questions

What does the evidence show about PCSK9 inhibitors (evolocumab / alirocumab / inclisiran)'s effects?
Read Off Label rates the evidence for PCSK9 inhibitors (evolocumab / alirocumab / inclisiran) as Strong and the benefit magnitude as very strong, producing an overall grade of S (8.7/10). Reserved historically for familial hypercholesterolemia, statin intolerance, or high-risk secondary prevention with inadequate LDL on maximal statin.
What safety findings are reported for PCSK9 inhibitors (evolocumab / alirocumab / inclisiran)?
PCSK9 inhibitors (evolocumab / alirocumab / inclisiran) has a low risk profile in the database. Low (injection site reactions; very clean systemic profile) Legal status: Rx (expensive at list; list prices now lower — ~$500-600/month after 2018 price cuts); enlicitide (Lipfendra) adds an oral option, FDA-approved July 2026.
What doses or routes are reported for PCSK9 inhibitors (evolocumab / alirocumab / inclisiran)?
Evolocumab 140 mg subQ q2wk or 420 mg monthly; alirocumab 75-150 mg subQ q2wk; inclisiran 284 mg subQ at 0, 3 mo, then every 6 mo; enlicitide (Lipfendra) 20 mg PO once daily This is context from studies, approved labeling, clinical practice, or documented use; it is not individualized guidance and does not establish safety.
How does PCSK9 inhibitors (evolocumab / alirocumab / inclisiran) work?
Block PCSK9 (which degrades LDL receptors) — resulting LDL receptor recycling drives circulating LDL-C down 50-60% on top of statin; inclisiran is siRNA silencing PCSK9 mRNA, dosed every 6 months

This is an independent synthesis of published research by a non-clinician. Scores are opinions supported by citations, not prescriptions. See the full disclaimer and methodology for how this score was produced and what it does and doesn't mean.