Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are among the most potent LDL cholesterol-lowering therapies available. Four FDA-approved products now compete in this space: two monoclonal antibodies (Repatha and Praluent), one small interfering RNA therapy (Leqvio), and a recently approved third-generation PCSK9-binding protein (Lerochol). The class generated $3.7 billion in combined global revenue in 2024, with growth accelerating as expanded indications and new entrants broaden the treatable population.
This landscape guide is for prescribers, access teams, pharmacists, and payer professionals who need a cross-PCSK9 view of coverage, prior authorization, step therapy, and cost trends.
FDA-approved PCSK9-targeting therapies at a glance
| Parameter | Repatha | Praluent | Leqvio | Lerochol |
|---|---|---|---|---|
| Generic name | Evolocumab | Alirocumab | Inclisiran | Lerodalcibep-liga |
| Manufacturer | Amgen | Regeneron/Sanofi | Novartis | LIB Therapeutics |
| Mechanism | mAb (binds PCSK9) | mAb (binds PCSK9) | siRNA (degrades PCSK9 mRNA) | Adnectin (binds PCSK9) |
| FDA approval | Aug 2015 | Jul 2015 | Dec 2021 | Dec 2025 |
| Route | SC injection | SC injection | SC injection (HCP-administered) | SC injection (self-administered) |
| Dosing frequency | Every 2 weeks or monthly | Every 2 weeks | Day 1, Day 90, then every 6 months | Monthly |
| Room-temp stability | Limited | Limited | Requires refrigeration | Up to 3 months |
| CV outcomes trial | FOURIER | ODYSSEY OUTCOMES | ORION-4 (ongoing) | Not yet completed |
FDA-approved indications
| Indication | Repatha | Praluent | Leqvio | Lerochol |
|---|---|---|---|---|
| Primary hyperlipidemia (adults) | Yes | Yes | Yes | Yes |
| Heterozygous FH (adults) | Yes | Yes | Yes | Yes |
| Heterozygous FH (pediatric ≥10 y) | Yes | No | No | No |
| Homozygous FH | Yes | No | No | No |
| CV risk reduction (established CVD) | Yes | Yes | No | No |
| CV risk reduction (at-risk, no prior CVD) | Yes (Aug 2025) | No | No | No |
In August 2025, the FDA broadened Repatha's indication to include adults at increased risk for major adverse cardiovascular events (MACE) due to uncontrolled LDL-C, even without a prior cardiovascular disease diagnosis. This expansion into primary prevention significantly broadened the eligible population. Leqvio received its own label expansion in July 2025, enabling first-line monotherapy use (without a required statin background) for adults with hypercholesterolemia, including HeFH.
Lerochol (lerodalcibep-liga), approved December 15, 2025, is the newest entrant. It is a third-generation PCSK9 inhibitor self-administered once monthly with extended room-temperature stability. It launched commercially in the US on May 11, 2026, with a direct-to-patient cash-pay option priced at $199 per month.
Pricing and cost
| Drug | Approximate annual WAC | List-price reduction | Notes |
|---|---|---|---|
| Repatha | $5,850 (reduced NDC) | 60% reduction from original $14,100 | Lower-priced NDC available since 2019; older NDCs may still be dispensed |
| Praluent | $5,850 (reduced NDC) | 60% reduction from original $14,600 | Lower-priced NDC available; requires pharmacy awareness |
| Leqvio | ~$6,500 | N/A | HCP-administered; buy-and-bill model common |
| Lerochol | ~$2,388 ($199/month cash-pay) | N/A | Launched May 11, 2026; direct-to-patient cash-pay option; prefilled syringe available |
Both Amgen (Repatha) and Regeneron/Sanofi (Praluent) reduced list prices by approximately 60% in 2018-2019. The Family Heart Foundation has reported that not all patients receive the lower-priced NDC, with some still facing higher out-of-pocket costs when pharmacies dispense under the older codes.
Repatha generated $2.2 billion in global revenue in 2024, making it the dominant PCSK9 agent. Leqvio reached $754 million in 2024 revenue and is on track to become the first blockbuster RNAi drug.
Formulary placement and prior authorization
Commercial insurance
PCSK9 inhibitors are uniformly placed on specialty tiers and require prior authorization. Step therapy through statins and ezetimibe is standard.
| Payer | Preferred agent | Step therapy requirements | Notes |
|---|---|---|---|
| UnitedHealthcare | Repatha (primary), Praluent (after Repatha failure) | Max tolerated statin x12 wk + ezetimibe | Not combined with Leqvio or other PCSK9i |
| Prime/HCSC | Repatha preferred | Statin failure + ezetimibe | Praluent non-preferred; requires Repatha failure |
| Cigna | Repatha preferred | Statin + ezetimibe | LDL thresholds: ≥70 mg/dL (ASCVD) or ≥100 mg/dL (non-ASCVD) |
| Mass General Brigham | Repatha preferred | Statin trial x12 wk; LDL threshold | Praluent requires Repatha failure first (effective Jan 2026) |
| CarelonRx | Repatha or Praluent | Statin + ezetimibe | LDL thresholds vary by ASCVD status |
| BCBS Michigan | Repatha or Praluent | Max tolerated statin + ezetimibe | Leqvio addressed separately |
Typical prior authorization criteria
For primary hyperlipidemia and HeFH, commercial payers generally require:
- Diagnosis of hyperlipidemia or HeFH confirmed by clinical criteria or genetic testing
- Trial and failure of maximally tolerated statin therapy for at least 12 weeks, OR intolerance to at least two statins, OR contraindication to all statins
- Trial and failure of ezetimibe for at least 12 weeks (or documented intolerance)
- Baseline LDL-C above threshold while on statin therapy (commonly ≥70 mg/dL with ASCVD, ≥100 mg/dL without ASCVD)
- Not used in combination with another PCSK9 inhibitor or Leqvio
- Authorization typically granted for 12 months; continuation requires demonstrated LDL reduction
For ASCVD/cvd risk reduction:
- Documented history of ACS, MI, stable/unstable angina, coronary revascularization, TIA, stroke, or peripheral arterial disease
- On maximally tolerated statin therapy (or documented statin intolerance)
- LDL-C remains above threshold (commonly ≥70 mg/dL)
For homozygous FH (Repatha only):
- Diagnosis confirmed by genetic testing (bi-allelic pathogenic variants) or clinical criteria (untreated LDL-C >400 mg/dL with xanthomas before age 10 or evidence of HeFH in both parents)
- Currently receiving other lipid-lowering therapy
- Age 10 years or older
Medicare Part D
PCSK9 inhibitors are covered under Medicare Part D. Some Medicare plans have shifted formulary positioning:
- BCBSM Medicare removed Repatha from its 2026 formulary, substituting Praluent as the covered PCSK9 inhibitor with prior authorizations pre-loaded for patients transitioning from Repatha
- The IRA negotiated-price program does not currently include any PCSK9 inhibitor, but the class's high Part D spending makes future selection possible
New entrant: Lerochol
Lerochol (lerodalcibep-liga) received FDA approval on December 15, 2025. Key differentiators:
- Once-monthly self-administration via prefilled syringe (autoinjector pen expected later in 2026)
- Room-temperature stability for up to 3 months, addressing a key storage barrier for Repatha and Praluent
- Adnectin-based mechanism: a recombinant fusion protein that binds PCSK9, distinct from the monoclonal antibody mechanism of Repatha and Praluent
- Phase 3 data: sustained LDL-C reductions of 50% or more in HeFH patients; 58.6% placebo-adjusted LDL-C reduction in the LIBerate-HeFH trial
- Indication: adjunct to diet and exercise for LDL-C reduction in adults with hypercholesterolemia, including HeFH. No CV outcomes data yet.
- Pricing and access: Launched May 11, 2026 with a direct-to-patient cash-pay option at $199 per month, substantially below other PCSK9 inhibitor cash prices
Payer coverage criteria for Lerochol are still being established but will likely follow the same statin-first step therapy pattern as existing PCSK9 inhibitors. The drug's room-temperature stability, monthly dosing, and competitive cash pricing may support formulary preference.
Patient assistance and copay support
| Drug | Copay assistance program | Notes |
|---|---|---|
| Repatha | Repatha Ready | Commercial patients may pay as low as $0/month; income-based PAP for uninsured |
| Praluent | Praluent Copay Card | Commercial patients; maximum benefit limits apply |
| Leqvio | Novartis patient support | HCP-administered; assistance with benefit investigation |
| Lerochol | Direct-to-patient cash-pay ($199/month) | Commercially available since May 2026; insurance coverage criteria pending |
What to monitor
Repatha primary-prevention expansion. The August 2025 label expansion to include adults at increased CV risk without prior CVD dramatically broadens the eligible population. Payer adoption of this broader indication will determine real-world access.
Lerochol launch and pricing. Launched May 11, 2026 at $199/month cash-pay. Payer coverage criteria, formulary positioning, and early utilization data will shape the competitive dynamics of the class. Autoinjector pen approval expected later in 2026.
ORION-4 CV outcomes trial (Leqvio). Expected completion in 2026. Positive results could support a CV risk reduction indication for Leqvio, transforming its payer positioning from LDL-lowering adjunct to outcomes therapy.
BCBSM Medicare formulary exclusion of Repatha. If other Medicare plans follow BCBSM's move to exclude Repatha in favor of Praluent, this could meaningfully shift market share and patient access patterns.
PCSK9 inhibitor IRA selection. The class is a candidate for future IRA negotiation rounds given its high Part D spending. Inclusion in a future negotiated-price cohort would significantly alter the pricing landscape.
Sources
- Amgen. "Repatha (evolocumab) Prescribing Information." 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/125522s032lbl.pdf
- Amgen. "Repatha Now Indicated for Adults at Increased Risk for Major Adverse Cardiovascular Events." August 25, 2025. https://www.amgen.com/newsroom/press-releases/2025/08/repatha-now-indicated-for-adults-at-increased-risk-for-major-adverse-cardiovascular-events-due-to-uncontrolled-ldl-c
- UnitedHealthcare. "Praluent Prior Authorization/Medical Necessity." Program 2025 P 2062-21. https://www.uhcprovider.com/content/dam/provider/docs/public/prior-auth/drugs-pharmacy/commercial/h-p/PA-Med-Nec-Praluent.pdf
- Prime Therapeutics. "PCSK9 Inhibitors Prior Authorization with Quantity Limit." HCSC Commercial, effective May 15, 2026. https://www.myprime.com/content/dam/prime/memberportal/forms/AuthorForms/HCSC/Program_Summaries/HCSC_PCSK9_Inhibitors_ProgSum.pdf
- Mass General Brigham Health Plan. "PCSK9 Inhibitors: Repatha and Praluent." Effective January 1, 2026. https://resources.massgeneralbrighamhealthplan.org/pharmacy/PharmacyPolicies/CommercialPolicies/PCSK9_PA_ComExch_Rx_1.1.2026.pdf
- CarelonRx. "PCSK9 Inhibitor Clinical Criteria." CC-0010, publish date October 1, 2025. https://www.carelonrx.com/ms/pharmacyinformation/PCSK9Inhibitor.pdf
- BCBS Michigan. "Medical Policy: PCSK9 Inhibitors." 2157725. https://www.bcbsm.com/amslibs/content/dam/public/mpr/mprsearch/pdf/2157725.pdf
- FDA. "Leqvio (inclisiran) Prescribing Information." Revised July 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/214012s016lbl.pdf
- LIB Therapeutics. "FDA Approves LEROCHOL (lerodalcibep-liga)." December 15, 2025. https://libtherapeutics.com/news-and-events/us-food-and-drug-administration-approves-lib-therapeutics-lerochol-for-adults-with-elevated-ldl-cholesterol.html
- LIB Therapeutics. "LIB Therapeutics Launches LEROCHOL in the United States with a Patient-First Approach to Access and Affordability." May 11, 2026. https://libtherapeutics.com/news-and-events/lib-therapeutics-launches-lerochol-in-the-united-states-with-a-patient-first-approach-to-access-and-affordability.html
- AJMC. "FDA Approves Once-Monthly PCSK9 Injection for LDL-C Reduction." December 2025. https://www.ajmc.com/view/fda-approves-once-monthly-pcsk9-injection-for-ldl-c-reduction
- Family Heart Foundation. "Action Alert: Getting the Lower List Price for PCSK9 Inhibitors." https://familyheart.org/lower-price-pcsk9i
- Cigna. "PCSK9 Inhibitors — Repatha Prior Authorization Policy." 2025. https://static.cigna.com/assets/chcp/pdf/coveragePolicies/cnf/cnf_605_coveragepositioncriteria_proprotein_convertase_subtilisin_kexin_type_9_inhibitors_repatha_pa.pdf
