Global Oligonucleotide Therapeutics Sales Top 10 List for 2023 Released: Total Revenue Reaches $4.32 Billion

In 2023,RNAi Cholesterol-Lowering New Drug Leqvio (Inclisiran)Total sales reached $355 million, a year-on-year increase of 217% — becoming one of the key drivers of sales growth for Novartis. Novartis stated that Leqvio also achieved good results in the early days in China's self-pay market.

Leqvio was approved by the FDA in December 2021 for the treatment of adult patients with elevated low-density lipoprotein cholesterol (LDL-C) who are on maximum tolerated statin therapy. Leqvio was acquired by Novartis for $9.7 billion through the acquisition of The Medicines Company.AlnylamAs the original research enterprise of this drug, stillEntitled to 10% of its global net sales as a sales royaltyCurrently, Leqvio has been approved in 94 countries/regions worldwide. Novartis is further expanding its approval scope, enhancing patient enrollment, eliminating access barriers, and strengthening medical education to further boost Leqvio's sales potential.

Leqvio's rapid increase in usage within a short period is closely related to the unique advantages of small nucleic acid drugs.Compared with PCSK9 monoclonal antibodies, Leqvio, which also targets PCSK9, not onlyAchieved a lipid-lowering effect that was not much different., also greatlyReduced the frequency of administration(Only two injections per year), compared to PCSK9 monoclonal antibodies that require dosing once every two weeks or once a month,Better patient complianceThis is all thanks to chemical modifications and delivery systems represented by GalNAc, which have significantly improved the stability and delivery/uptake efficiency of small nucleic acid drugs, allowing for substantial optimization in dosing methods, frequency, and dosage.

Developed by AlnylamOnpattro isThe first commercially available RNAi therapeutic product to receive FDA approval, with sales of $355 million in 2023, a year-on-year decrease of 36.4%. This was mainly due to the sales decline caused by drug iteration, with the new generation of drugsAmvuttra has a long dosing interval.Patient'sBetter compliance, the patient quickly completed the dressing change,Onpattro Sales Decline, Amvuttra Rises Rapidly。

In order to prevent Onpattro from losing commercial value, Alnylam Pharmaceuticals once attempted to expand the indication label for Onpattro. In February last year, Alnylam submitted a supplemental New Drug Application (sNDA) to the FDA to extend the use of Onpattro for treating transthyretin amyloid cardiomyopathy (ATTR-CM). However, it was unfortunately rejected by the U.S. FDA due to "no significant clinical treatment effect."

Casimersen (Amondys 45), developed by Sarepta, achieved $270 million in sales in 2023, representing a 28% year-over-year increase, ranking sixth on the list.

Casimersen was approved by the FDA on February 25, 2021, for DMD patients with exon 45 skipping mutations. Amondys 45 has become the third ASO therapy for DMD gene mutations to be approved in the United States, following Exondys 51 and Vyondys 53. This is alsoFDA Approves First Targeted Therapy for Patients with This Mutation。

Givlaari, developed by Alnylam, generated $220 million in sales in 2023, a 27% year-over-year increase, ranking seventh.

In November 2019, the FDA approved givosiran for marketing to treat acute hepatic porphyria (AHP) in adults. By the end of 2023, more than 650 patients worldwide are receiving commercial Givlaari treatment.More than 430 patients are receiving commercialized Oxlumo treatment.

Golodirsen (Vyondys 53), developed by Sarepta, achieved $130 million in sales in 2023, representing an 11% year-over-year increase, ranking eighth.

Golodirsen is a Sarepta patented phosphorodiamidate morpholino oligomer compound designed to bind to exon 53 of the dystrophin pre-mRNA, thereby excluding or "skipping" this exon during mRNA splicing.

NS Pharma (Nippon Shinyaku)'s Viltepso (viltolarsen) official website released the sales forecast data for 2023. The actual sales from April to December 2023 were 13,225 million yen, with an estimated total sales of 18,300 million yen (approximately 130 million USD) for the entire year of 2023, ranking ninth.

Viltepso is an antisense oligonucleotide (ASO) drug that works by skipping exon 53, converting out-of-frame deletions in the DMD gene to in-frame deletions in some patients to alleviate symptoms. It can bind to the pre-mRNA at the position of exon 53 of the DMD gene and, after the formation of mature mRNA, remove the portion of exon 53, thereby partially restoring the mRNA reading frame. The method of administration is intravenous infusion.March 25, 2020Viltepso®Approved for Marketing in JapanIt was approved for marketing in the United States on August 19 of the same year, for the treatment of Duchenne muscular dystrophy (DMD) caused by exon 53 skipping mutations in the DMD gene.

Oxlumo (lumasiran), developed by Alnylam, generated $110 million in sales in 2023, representing a 57% year-over-year increase, ranking tenth. Oxlumo was approved by the U.S. FDA on November 23, 2020.The first FDA-approved drug for the treatment of Primary Hyperoxaluria Type 1 (PH1). Meanwhile, this is the third RNAi therapy approved from Alnylam Pharmaceuticals.

Oxlumo is an RNAi therapy targeting hydroxyacid oxidase 1 (HAO1) mRNA. HAO1 is involved in encoding glycolate oxidase (GO), an upstream enzyme that can lead to PH1 deficiency. Lumasiran reduces GO synthesis and inhibits oxalate production by degrading HAO1 mRNA.

The indications of marketed small nucleic acid drugs are mostly concentrated in the field of rare diseases, such as Duchenne muscular dystrophy, spinal muscular atrophy, etc., with a limited patient population. AndThe long-acting lipid-lowering drug Inclisiran (Leqvio) has pioneered the use of small nucleic acid drugs for chronic conditions.Major companies are leveraging existing pipelines to focus on key collaborations for cardiovascular and metabolic disease indications with large patient populations. It is expected that as breakthroughs in these indications continue, small nucleic acid drugs will reach a new turning point in development.