Novartis has secured FDA approval for its cholesterol-lowering drug Leqvio (inclisiran), marking a significant milestone for the first-in-class small interfering RNA (siRNA) therapy that requires only two injections per year. The approval comes after a year-long delay and positions the drug to compete in the challenging PCSK9 inhibitor market.
Breakthrough Dosing Advantage
Leqvio represents a major advancement in cholesterol management, offering the same PCSK9 inhibition mechanism as existing antibody therapies but with dramatically reduced dosing frequency. While Amgen's Repatha (evolocumab) and Sanofi/Regeneron's Praluent (alirocumab) require monthly injections, Leqvio maintains efficacy with just two doses annually after an initial lead-in period.
The FDA approved Leqvio as an adjunct to maximum-dose statin drugs for people who need further LDL-cholesterol reduction to reach targets. The drug will launch in the US in January, according to Novartis.
Strong Clinical Performance
In the pivotal phase 3 ORION-9, ORION-10, and ORION-11 trials, adding Leqvio to statins achieved LDL-cholesterol reductions of up to 52% versus placebo in people with high cholesterol and atherosclerotic cardiovascular disease (ASCVD). This efficacy profile positions the drug competitively against existing PCSK9 inhibitors while offering superior convenience.
The clinical data addresses a substantial unmet need, with approximately 16 million people in the US with ASCVD who are taking statins to lower cholesterol – including those who have experienced a heart attack or stroke – not reaching their recommended LDL-cholesterol target.
Manufacturing Hurdle Overcome
The approval follows a challenging regulatory journey. The FDA initially issued Novartis a complete response letter (CRL) a year ago, citing "unresolved facility inspection-related conditions" at a third-party manufacturing site run by Corden Pharma near Milan, Italy. Novartis successfully addressed these concerns by transferring fill-and-finish production to its own facility in Schaftenau, Austria, and resubmitted the marketing application earlier this year.
Market Dynamics and Competition
Novartis faces a competitive landscape where existing PCSK9 inhibitors have struggled with uptake despite substantial price cuts. However, there are signs of momentum building, with Repatha seeing a 33% increase in sales to $272 million in the third quarter, finally approaching the blockbuster run rate predicted at its 2015 approval. Praluent, which also debuted in 2015, is performing less favorably with €59 million ($67 million) for Sanofi and $45 million for Regeneron in the same period.
The company added inclisiran to its pipeline through the $9.7 billion acquisition of The Medicines Company in 2019, which had licensed the drug from Alnylam. Early European sales of just $5 million in the third quarter reflect the typical lag between regulatory approval and reimbursement negotiations, though the UK's NICE agreed to an access deal in August.
Future Cardiovascular Outcomes Data
While Leqvio demonstrates strong LDL cholesterol reduction, Novartis is conducting additional studies to prove cardiovascular outcomes benefits – data that both Repatha and Praluent already possess. The company must await results from the ORION-4 study, due in 2026, before potentially matching the comprehensive labels of competing therapies.
The approval represents a critical step for Novartis in establishing a foothold in the cholesterol management market, with the convenience of twice-yearly dosing potentially driving adoption where previous PCSK9 inhibitors faced payer resistance.
