Inclisiran (Leqvio): PCSK9 Landscape and Competitors

Inclisiran, sold by Novartis as Leqvio, is a twice-yearly injection that lowers LDL cholesterol and is growing quickly. Novartis reported Leqvio sales of $506 million in the third quarter of 2026, up 64% from $308 million a year earlier. Its next test is outcomes data: as of November 4, 2026, no inclisiran trial has reported whether it reduces heart attacks and strokes.

Mechanism at a glance

Inclisiran is a small interfering RNA (siRNA) given by a health care provider: an initial dose, a second at three months, then every six months (Novartis). In the ORION-10 and ORION-11 trials, LDL cholesterol fell 52.3% and 49.9% versus placebo at day 510; injection-site reactions were more frequent with inclisiran (2.6% vs 0.9% and 4.7% vs 0.5%) but generally mild (Europe PMC). In ORION-9, in 482 adults with heterozygous familial hypercholesterolemia, the figures were a 39.7% fall versus an 8.2% rise on placebo (Europe PMC).

Why it matters

Two US label changes widened its use. On July 31, 2025, the FDA approved Leqvio as monotherapy alongside diet and exercise, removing the need to use it with a statin; Novartis said the FDA requested the update (Novartis). Novartis announced on August 19, 2026 that the label was updated to recognize that lowering LDL-C reduces the risk of major adverse cardiovascular events in adults at increased risk. Novartis said this draws on evidence from statins and PCSK9 antibodies, not on inclisiran outcome data (Novartis).

Competitive pressure points

• Antibodies with outcomes data: in VESALIUS-CV (12,257 patients without a prior heart attack or stroke), evolocumab reduced 3-point MACE (hazard ratio 0.75) and 4-point MACE (0.81) over a median 4.6 years (NEJM via Europe PMC). Alirocumab had a primary-composite hazard ratio of 0.85 after acute coronary syndrome in ODYSSEY OUTCOMES (Europe PMC).
• Oral PCSK9: Merck’s enlicitide (Lipfendra) was approved by the FDA on July 16, 2026 as a once-daily 20 mg tablet; CORALreef Lipids showed a 55.8% adjusted LDL-C difference versus placebo, and its outcomes trial (more than 14,500 enrolled) has no results yet (TCTMD). AstraZeneca’s AZD0780 is in the Phase 3 AZURE-Outcomes trial, with an estimated 15,100 participants and an estimated primary completion in October 2029 (ClinicalTrials.gov).
• Monthly dosing: lerodalcibep (Lerochol) was announced as FDA-approved on December 15, 2025 as a once-monthly self-injection (TCTMD).
• A different mechanism: obicetrapib won EU authorization in September 2026; see our obicetrapib landscape.

What to watch

• Inclisiran outcomes: Novartis expects the secondary-prevention trials ORION-4 and VICTORION-2-PREVENT to read out in 2027. ClinicalTrials.gov lists 16,124 patients in ORION-4 and 17,004 in VICTORION-2 PREVENT; registry dates are estimates (see our guide to registry records).
• VICTORION-1 PREVENT, the primary-prevention trial (14,012 patients), has an estimated primary completion of April 2029.
• The effect of oral enlicitide on injectable uptake, and of Leqvio patent litigation: Novartis reports US ANDA litigation with a generic manufacturer.

Recent developments

Updated November 4, 2026. Items are drawn from company announcements, regulators and trade press; links go to the sources.

• Oct 27, 2026: Novartis reported Q3 Leqvio sales of $506 million (up 64% in US dollars, 63% at constant currency) and nine-month sales of $1,438 million, citing growth across all regions and continued China uptake after its January national reimbursement listing. (Novartis 6-K)
• Aug 19, 2026: Novartis announced that the FDA updated the Leqvio label to recognize MACE risk reduction from LDL-C lowering. (Novartis)
• Jul 16, 2026: FDA approved enlicitide (Lipfendra). (TCTMD)
• Nov 8, 2025: VESALIUS-CV was published online in the New England Journal of Medicine. (Europe PMC)
• Jul 31, 2025: FDA approved the Leqvio monotherapy label. (Novartis)

Upcoming catalysts

• 2027: Novartis-guided readouts of ORION-4 and VICTORION-2-PREVENT; Novartis’s pipeline table lists a first submission for secondary prevention in 2027 (Novartis 6-K).
• April 2029 (estimated): VICTORION-1 PREVENT primary completion.

Bottom line

Leqvio is growing quickly on the strength of LDL lowering and convenient dosing, but its rivals already hold outcomes data or oral dosing. The 2027 readouts will show whether inclisiran can close that gap.

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This article is for informational and competitive-intelligence purposes only and is not medical advice. Approvals, labels and trial results change; verify details against current prescribing information and primary sources.