Praluent (Alirocumab) Global Regulatory Status: FDA Approval, EMA Authorization, and Label Updates
Praluent is the brand name for alirocumab, a monoclonal antibody that inhibits PCSK9 (proprotein convertase subtilisin/kexin type 9) and is given as a subcutaneous injection. It is co-marketed by Regeneron Pharmaceuticals and Sanofi and should not be confused with evolocumab (Repatha), the other approved PCSK9-inhibitor antibody, or with inclisiran (Leqvio), a PCSK9-targeting siRNA that works through a different mechanism and dosing schedule.
The direct answer: the FDA approved alirocumab on July 24, 2015 (BLA 125559) for LDL-C lowering in adults with heterozygous familial hypercholesterolemia (HeFH) or established atherosclerotic cardiovascular disease already on maximally tolerated statin therapy. The FDA added a cardiovascular risk-reduction indication in April 2019, based on the ODYSSEY OUTCOMES trial in patients with a recent acute coronary syndrome, and the European Medicines Agency authorized the same original indication in September 2015 with a parallel cardiovascular label update in 2019. Current FDA labeling carries no boxed warning and no REMS requirement (per the FDA's 2019 label revision).
This page focuses on what the FDA, EMA, and their published documents actually say, and separates that from claims that require verification against the primary trial papers before a clinician or patient should treat them as settled.
What the FDA approved, and when
The FDA approved alirocumab on July 24, 2015, making it the first PCSK9 inhibitor cleared for U.S. marketing, ahead of evolocumab by about a month. The original label covered adults with HeFH or clinical ASCVD who needed additional LDL-C lowering on top of diet and maximally tolerated statin therapy. The original prescribing information specified 75 mg and 150 mg doses given subcutaneously every two weeks, with a titration strategy: start at 75 mg and move to 150 mg if the LDL-C response after 4 to 8 weeks was insufficient (source: 2015 FDA label, https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/125559Orig1s000lbl.pdf).
Approval was supported by a program of Phase 3 ODYSSEY trials. Published descriptions of this program report LDL-C reductions in the 40-60% range relative to placebo or ezetimibe across different trials in the series. The exact per-trial magnitude (for example, the specific percentage reported in ODYSSEY COMBO II) should be verified against the original journal article rather than taken from a secondary summary, since trial-specific numbers are easy to misattribute across the multiple ODYSSEY studies.
In April 2019, the FDA approved a supplemental BLA adding a second indication: reducing the risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with established cardiovascular disease. The current label therefore carries two indications rather than one (per the FDA's 2019 label revision). A third dosing option, 300 mg every four weeks, was added to give patients who prefer monthly dosing an alternative to the every-two-week schedule.
What the ODYSSEY OUTCOMES trial actually supports
ODYSSEY OUTCOMES was a large, randomized, placebo-controlled cardiovascular outcomes trial in patients who had an acute coronary syndrome event 1 to 12 months before enrollment and were already on high-intensity or maximum-tolerated statin therapy. It is the trial that supports the 2019 cardiovascular indication. Published reports describe a 15% relative reduction in the composite primary endpoint (cardiovascular death, nonfatal MI, ischemic stroke, or unstable angina requiring hospitalization), with the effect appearing larger in patients whose baseline LDL-C was 100 mg/dL or higher.
An exploratory, non-multiplicity-adjusted analysis of all-cause mortality has also been reported for this trial. Because this analysis was exploratory rather than a pre-specified, hierarchically tested endpoint, it should be read as a nominal finding that generated a hypothesis rather than as confirmed evidence of a mortality benefit. Readers who need the exact hazard ratios, confidence intervals, and statistical testing hierarchy for either the primary MACE endpoint or the mortality analysis should verify these against the original New England Journal of Medicine publication rather than rely on any single secondary summary, including this one; specific figures circulating online for this trial have not been independently re-verified for this draft.
A previous version of this page attributed a direct quotation to one of the trial's investigators. That quotation could not be independently verified against a citable source and has been removed rather than repeated.
EMA authorization and other regulators
The European Commission granted marketing authorization for Praluent on September 23, 2015, following a positive opinion from the Committee for Medicinal Products for Human Use. The approved European indication matched the original U.S. indication: hypercholesterolemia or mixed dyslipidemia, used with a statin or other lipid-lowering therapy in patients who cannot reach LDL-C goals on maximally tolerated statin, or alone in statin-intolerant patients or those for whom a statin is contraindicated. The EMA's European Public Assessment Report (EPAR) is the authoritative source for the exact wording and history of this authorization, including the 2019 cardiovascular label update (https://www.ema.europa.eu/en/medicines/human/EPAR/praluent).
Reports describing approval by Japan's PMDA in 2016 and by Health Canada in the same period are consistent with the drug's known international rollout, but a reader who needs the exact approval dates and indication wording for those jurisdictions should confirm them against the respective national regulator, since this draft does not have a verified primary source for those specific dates.
Post-market safety: what has and has not changed since approval
Since 2015, neither the FDA nor the EMA has added a boxed warning or mandated a Risk Evaluation and Mitigation Strategy (REMS) for alirocumab. The FDA Adverse Event Reporting System (FAERS) public dashboard is the primary source for checking whether new safety signals have emerged since approval (https://www.fda.gov/drugs/questions-and-answers-fdas-adverse-event-reporting-system-faers/fda-adverse-event-reporting-system-faers-public-dashboard). At the time this draft was prepared, no FDA-communicated safety signal beyond the adverse events already described in the original label (injection-site reactions, hypersensitivity reactions, upper respiratory tract infection) had been identified in that dashboard; this status should be rechecked at the FAERS dashboard directly, since it updates over time and any statement about "no new signal" is time-bound.
A prospective neurocognitive substudy conducted within the ODYSSEY OUTCOMES trial has been reported as finding no significant difference in neurocognitive adverse events between alirocumab and placebo, including among patients who reached very low LDL-C levels. This is a specific, testable claim; a clinician relying on it for a patient concerned about cognitive effects at very low LDL-C should confirm the finding against the substudy's own publication rather than this summary.
Alirocumab versus evolocumab: what is a genuine regulatory difference and what is not
Evolocumab (Repatha) received FDA approval about a month after alirocumab, in August 2015, and its cardiovascular indication (based on the FOURIER trial) was approved in December 2017, ahead of alirocumab's 2019 cardiovascular indication. Evolocumab also carries an FDA indication for homozygous familial hypercholesterolemia (HoFH) in patients 10 and older; alirocumab does not hold this indication. These are real, checkable regulatory differences (evolocumab BLA history: https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=125522).
What is not established is that one drug is clinically superior to the other for cardiovascular risk reduction. FOURIER and ODYSSEY OUTCOMES enrolled different populations (stable ASCVD versus recent acute coronary syndrome) and used different composite endpoints (FOURIER included coronary revascularization; ODYSSEY OUTCOMES did not). The two trials have never been compared head-to-head, so a reported similar relative risk reduction in both trials does not mean the drugs have equivalent cardiovascular benefit in the same population. Any claim that alirocumab has a "mortality advantage" over evolocumab based on comparing an exploratory, non-adjusted analysis in one trial against a null result in a different trial with a different design is not a valid inference and should not be presented as settled evidence.
Cost, access, and biosimilar status
Regeneron and Sanofi reduced Praluent's U.S. list price by roughly 60% in a 2018 announcement, from an initial list price near $14,000 per year to approximately $5,850 per year. List price is not the same as what a given patient or plan actually pays after rebates, and this figure should be treated as a 2018 manufacturer statement rather than a current price; a reader needing an up-to-date price should check a current pharmacy benefit source rather than this figure.
The Institute for Clinical and Economic Review (ICER) has published cost-effectiveness assessments of the PCSK9 inhibitor class, initially judging the drugs cost-ineffective at launch pricing and revising that assessment after the price reduction and the publication of cardiovascular outcomes data. The specific dollar-per-QALY thresholds ICER used should be read directly from that assessment rather than restated as a fixed number, since ICER updates its models over time.
Most commercial and Medicare Part D plans still require prior authorization, typically documenting an ASCVD or HeFH diagnosis, an LDL-C level above a plan-specific threshold, maximally tolerated statin use, and a documented trial of ezetimibe. CMS has issued guidance to Part D sponsors on PCSK9 inhibitor utilization management (https://www.cms.gov), but exact criteria vary by plan and should be confirmed with the specific payer rather than assumed from a general summary.
Alirocumab was approved under the Public Health Service Act as a biologic, which places it under the Biologics Price Competition and Innovation Act (BPCIA) rather than the small-molecule generic pathway. Its 12-year biologics exclusivity, counted from the July 2015 approval, means the earliest a biosimilar could plausibly be approved is around 2027. As of this review (May 2026), no biosimilar alirocumab application has been publicly disclosed, and the 2023 Supreme Court decision in Amgen Inc. v. Sanofi (which upheld invalidation of certain broad Amgen PCSK9 antibody patents on enablement grounds) removed one intellectual-property obstacle without guaranteeing a biosimilar timeline. This exclusivity date and disclosure status are volatile facts that should be rechecked closer to 2027.
Evidence boundary: what is established, plausible, and not established
Established, from FDA and EMA regulatory documents: the July 2015 FDA approval and its original indication; the April 2019 FDA cardiovascular indication addition; the September 2015 EMA authorization and its 2019 cardiovascular update; the absence of a boxed warning or REMS; the three FDA-approved dosing regimens; and alirocumab's status as a biologic under BPCIA with exclusivity dating from 2015.
Plausible but requiring verification against the primary trial papers before use in clinical decisions: the exact magnitude and confidence intervals of the ODYSSEY OUTCOMES primary endpoint reduction; the exploratory all-cause mortality signal from that trial; per-trial LDL-C reduction percentages across the individual ODYSSEY studies; and the neurocognitive substudy's precise findings.
Not established: that alirocumab is clinically superior or inferior to evolocumab on cardiovascular outcomes (the two pivotal trials were not head-to-head and used different endpoints and populations); a fixed, current-day list or net price; and a confirmed biosimilar approval timeline.
Decision framework: how a clinician or patient should read this regulatory history
The information provided here should not be construed as medical advice for any individual patient. Rather, it offers a structured approach to understanding the regulatory landscape surrounding alirocumab when questions about patient access or treatment arise.
| Situation | What the regulatory record actually supports | What it does not settle |
|---|---|---|
| Patient has HeFH or known ASCVD, LDL-C above goal on maximal statin | Alirocumab's original 2015 indication covers this population as an adjunct to statin therapy | Whether alirocumab or evolocumab is preferable here; both hold this general indication |
| Patient had an ACS event in the last year and remains on statin therapy | The 2019 cardiovascular indication was built specifically for this population (ODYSSEY OUTCOMES enrolled post-ACS patients) | The exact size of benefit for a given patient; verify trial-level hazard ratios in the primary paper before quoting a number to a patient |
| Patient is a child or adolescent with suspected homozygous FH | Alirocumab does not carry this indication | Evolocumab is the PCSK9 inhibitor with an FDA-approved pediatric HoFH indication; this is a real reason to prefer evolocumab in that specific population |
| Payer denies coverage or requires prior authorization | Standard PA criteria (ASCVD/HeFH documentation, LDL-C threshold, statin and ezetimibe trial) are well documented across Part D and commercial plans | The exact threshold and required documentation vary by plan; confirm with the specific payer rather than assuming a uniform national rule |
| Patient or clinician asks about long-term cognitive safety at very low LDL-C | A prospective substudy within ODYSSEY OUTCOMES reported no signal of increased neurocognitive events at low LDL-C | This is one substudy from one trial population; it should not be generalized to every possible LDL-C floor or every patient subgroup without checking the substudy's inclusion criteria |
| Patient asks when a cheaper biosimilar might be available | Biologics exclusivity runs to roughly 2027 at the earliest | No application has been publicly disclosed as of this review; an actual biosimilar launch could be later, and "earliest possible" is not "expected" |
The practical rule: use this table to decide what question to ask next (the payer, the specific trial paper, the current FAERS dashboard, or the current EPAR), not as a substitute for checking the underlying regulatory document when the answer will change what a patient is prescribed or billed.
When to involve a clinician directly
A patient experiencing a suspected hypersensitivity reaction, significant injection-site reaction, or new neurological or cognitive symptoms after starting alirocumab should contact the prescribing clinician rather than rely on general safety statements from this page. Anyone with signs of a severe allergic reaction (difficulty breathing, facial or throat swelling) needs urgent medical care.
References
- U.S. Food and Drug Administration. Praluent (alirocumab) original approval letter and prescribing information, 2015. https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/125559Orig1s000lbl.pdf
- European Medicines Agency. Praluent: European Public Assessment Report (EPAR). https://www.ema.europa.eu/en/medicines/human/EPAR/praluent
- U.S. Food and Drug Administration. BLA 125522: Repatha (evolocumab) approval and label history. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=125522
- U.S. Food and Drug Administration. FDA Adverse Event Reporting System (FAERS) public dashboard. https://www.fda.gov/drugs/questions-and-answers-fdas-adverse-event-reporting-system-faers/fda-adverse-event-reporting-system-faers-public-dashboard
- Centers for Medicare and Medicaid Services. https://www.cms.gov
Note for editorial and medical review: claims tied to specific PubMed identifiers in the prior draft of this page (ODYSSEY COMBO II results, ODYSSEY OUTCOMES hazard ratios, the FOURIER trial results, and the long-term extension study) have been described in general terms in this draft because the specific identifiers could not be independently re-verified against the correct paper. These should be checked against the primary literature and re-cited with confirmed links before publication. A quotation previously attributed to a named trial investigator has been removed because it could not be verified.