The narrative of the oligonucleotide field is no longer limited to the chapter on "technological breakthroughs."

 

Following the global oligonucleotide new drug market reaching US7.122billionin2025,withthreedrugsjoiningthe"blockbuster"ranks,thecommercializationofthesedrugscontinuedtoaccelerateinthefirstquarterof2026.CombinedrevenuesfrommarketedoligonucleotidedrugsexceededUS7.122billionin2025,withthreedrugsjoiningthe"blockbuster"ranks,thecommercializationofthesedrugscontinuedtoaccelerateinthefirstquarterof2026.CombinedrevenuesfrommarketedoligonucleotidedrugsexceededUS2.2 billion, representing approximately 45% year-over-year growth.

 

Alnylam entered the "US$1 billion quarterly revenue club" in a single quarter. Novartis's Leqvio saw a 76% year-over-year surge, driven by uptake in China's national医保 (medical insurance) system. Arrowhead's Plozasiran filled its first commercial prescriptions. GSK's Bepirovirsen for hepatitis B received FDA Priority Review.

 

These drugs not only demonstrate strong commercial momentum but also collectively outline a key trend: oligonucleotide drugs are no longer confined to rare diseases. Instead, they are targeting major indications, chronic diseases, and common conditions, offering long-acting advantages and rewriting the standard of care for these diseases.

 

A clear signal has emerged: the oligonucleotide track is mass-producing the next generation of blockbuster drugs.

 

TONACEA 01: Accelerating Uptake of Star Products

 

Currently, more than 20 oligonucleotide drugs have been approved globally, including ASOs, siRNAs, and aptamers, covering rare diseases, cardiovascular conditions, infectious diseases, and other areas.

 

Led by international companies, the R&D and commercialization of global oligonucleotide drugs have entered a comprehensive harvest period after years of accumulation.

 

Building on its profitability in 2025, in Q1 2026, driven by four self-commercialized siRNA drugs, Alnylam achieved product revenues of US1.036billion(1211.036billion(1211 billion quarterly revenue club."

 

Among these, global net product revenues for Amvuttra and Onpattro were US890millionandUS890millionandUS20 million, respectively, with combined TTR product net revenues of US910million,a153910million,a15374 million and US51million,respectively,withcombinedrarediseasenetproductrevenuesofUS51million,respectively,withcombinedrarediseasenetproductrevenuesofUS126 million, a 15% increase from Q1 2025.

 

Novartis's blockbuster oligonucleotide drug Leqvio® (inclisiran) achieved accelerated growth outside the United States, reaching blockbuster status in 2025. In Q1 2026, sales reached US$452 million, a massive 76% year-over-year increase.

 

Leqvio is a prescription injectable drug indicated for adult patients with hypercholesterolemia (including heterozygous familial hypercholesterolemia) as an adjunct to diet and exercise to reduce LDL-C levels.

 

In July 2025, Novartis announced that the FDA proactively proposed updating Leqvio's label. Based on the strong lipid-lowering data for PCSK9-targeting therapies, Leqvio could be used alone, without requiring concomitant statin therapy. The label's "primary hyperlipidemia" was revised to the more precise "hypercholesterolemia" to highlight its core role in LDL-C reduction.

 

This marks Leqvio's most groundbreaking label expansion since its approval, signaling a shift from being a "statin adjunct" to an "independent backbone" therapy, offering new treatment options for a broader patient population.

 

Leqvio is registered in over 107 countries and launched in 87. With its twice-yearly dosing regimen, Leqvio has unique advantages in improving patient adherence and achieving long-term lipid management.

 

Notably, Novartis noted in its earnings report that Leqvio's Q1 sales growth was driven by robust performance in China.

 

In the Chinese market, Leqvio was first approved in August 2023 for use in combination with statins or, in statin-intolerant patients, alone or with other non-statin therapies, for adults with primary hypercholesterolemia (heterozygous familial and non-familial) or mixed dyslipidemia.

 

During the 2025 National医保 (medical insurance) negotiations, Leqvio's indication was successfully included in the national reimbursement list, effective January 1, 2026. The price per injection was reduced from 9,988 RMB to below 3,000 RMB, a reduction of over 70%. After insurance reimbursement, out-of-pocket costs for patients fell to less than 300 RMB per injection.

 

In January 2026, Leqvio received NMPA approval for a new indication: as an adjunct to diet, as monotherapy for adults with primary hypercholesterolemia (non-familial) or mixed dyslipidemia to lower LDL-C.

 

With the label update and the implementation of the national reimbursement listing, Leqvio's commercialization achieved further acceleration. Novartis continues to promote the drug, and the significant growth acceleration for Leqvio in 2026 is expected to further boost global enthusiasm for oligonucleotide industry development.

 

TONACEA 02: Potential Blockbuster Drugs on the Horizon

 

While commercialized products are advancing strongly, several oligonucleotide drugs in development have also achieved breakthrough progress.

 

On April 28, Ionis Pharmaceuticals, in collaboration with GSK, announced that the FDA has accepted a New Drug Application (NDA) for Bepirovirsen (GSK3228836/GSK836) and granted it Priority Review. Bepirovirsen is an investigational antisense oligonucleotide (ASO) for the treatment of chronic hepatitis B (CHB) in adults. The FDA has granted Bepirovirsen Breakthrough Therapy designation and has set a Prescription Drug User Fee Act (PDUFA) target action date of October 26, 2026.

 

As the first oligonucleotide drug for CHB to complete Phase III studies, Bepirovirsen has now submitted marketing applications in major global markets, including the US, EU, Japan, and China.

 

CHB is a major public health challenge, affecting over 250 million people globally, including an estimated 75 million in China. Current standard-of-care treatments are typically nucleos(t)ide analogs requiring lifelong therapy, with low functional cure rates, generally around 1%. In China, approximately 450,000 people die annually from CHB.

 

Ionis CEO Brett P. Monia stated that as the first drug capable of achieving a clinically meaningful functional cure rate, Bepirovirsen has unique advantages in effectively treating CHB, with its potential to suppress HBV replication, suppress hepatitis B surface antigen, and stimulate the immune system.

 

In the cardiovascular field, on March 28, Arrowhead Pharmaceuticals announced long-term efficacy and safety data from an open-label extension (OLE) study of Plozasiran. The data support its potential as a therapeutic solution for a range of patients with hypertriglyceridemia (HTG).

 

In November 2025, Plozasiran was approved by the FDA for the treatment of familial chylomicronemia syndrome (FCS), offering a new targeted treatment option for patients with severe hypertriglyceridemia (sHTG) at risk of recurrent acute pancreatitis (AP). The drug requires only once-every-three-months subcutaneous injections for durable and stable disease management.

 

Subsequently, on January 6, Sanofi announced that Plozasiran received NMPA approval for FCS, filling a critical treatment gap in China.

 

In 2026, Arrowhead is in a pivotal transition period from R&D to commercialization. Plozasiran is being commercialized under a "uniform price" model of approximately US$60,000 per year. First commercial sales were achieved in Q1 2026, though Arrowhead did not disclose specific sales figures.

 

Arrowhead plans to complete the SHASTA-3, SHASTA-4, and MUIR-3 Phase III studies (designed to support regulatory submissions for Plozasiran in sHTG) by mid-2026, and to submit a supplemental NDA to the FDA by the end of 2026. Its commercialization pathway – moving from a rare to a common disease – is clearly defined.

 

Beyond hepatitis B and cardiovascular disease, oligonucleotides are also opening new possibilities in obesity.

 

On March 26, Wave Life Sciences updated Phase I INLIGHT trial data for its INHBE GalNAc-siRNA, WVE-007. The 240 mg group showed a 14.3% reduction in visceral fat at six months, while the 400 mg group showed a 5.0% reduction at three months.

 

WVE-007 is a GalNAc-conjugated siRNA targeting INHBE mRNA, designed to achieve "fat loss without muscle loss" by silencing the INHBE gene. Although the 400 mg high-dose group did not show a significant efficacy improvement compared to the data released in December 2025 – causing notable stock price volatility for Wave – its precision fat-loss mechanism still holds potential.

 

The FDA has accepted the multi-dose portion of the Phase IIa trial for WVE-007, which remains on track to begin in Q2 2026, targeting individuals with a BMI of 35-50 kg/m², with or without type 2 diabetes. Data from the Phase IIa study will inform further development of WVE-007 in obesity, as well as in MASH, type 2 diabetes, and cardiovascular disease.

 

In addition to initiating the Phase IIa multi-dose monotherapy study, Wave clearly stated in its latest strategic update that it will also initiate new clinical trials in 2026 evaluating WVE-007 as an add-on to incretin therapies and as a maintenance therapy following incretin withdrawal.

 

From functional cures for hepatitis B, to long-acting solutions for lipid management, to precision interventions for fat loss without muscle loss – these next-generation oligonucleotide drugs, still in development but already showing promise, are writing richer chapters in the era of blockbuster drugs.

 

TONACEA 03: The Global Transaction Race Continues

 

A clear pattern emerges when examining the development of these new oligonucleotide drugs: the combination of biotech's technological moats and MNCs' commercialization capabilities has collectively enabled the creation of these blockbuster molecules. BD and partnerships have become a key chapter in the oligonucleotide industry's narrative.

 

Insight Database shows that nearly 100 BD collaborations have been established in the global oligonucleotide field over the past three years. Both the number and value of deals have increased annually, with more than 30 BD deals in 2025 alone, representing a total transaction value of nearly US$30 billion.

 

This trend has accelerated further from early 2026 to the present, with participants including Genentech, Madrigal, GSK, and others. Recently, two oligonucleotide deals exceeding US$1 billion each have pushed this trend to new heights.

 

On May 6, Shian Biotech licensed global rights (excluding Greater China) to SA030, an siRNA drug already in Phase I clinical trials, to GSK. Under the agreement, GSK will pay an upfront payment and milestones, with the total potential deal value reaching up to US$1.005 billion.

 

SA030 targets activin receptor-like kinase 7 (ALK7), an established therapeutic mechanism for cardiometabolic diseases. Cardiometabolic disease is the leading cause of death for approximately 50% of patients with chronic kidney disease and liver disease.

 

Targeting ALK7 reduces abdominal fat (visceral adipose tissue, VAT) while preserving lean mass, thereby improving insulin sensitivity, lipid profiles, and reducing adipocyte-driven inflammation. A growing body of evidence links VAT with cardiometabolic risk. Among patients with chronic inflammatory diseases, reducing this metric has a greater impact on patient survival than solely managing the underlying condition.

 

Preclinical studies indicate that SA030 possesses a differentiated long-acting profile, addressing underlying inflammation linked to cardiometabolic risk through adipocyte-targeted delivery and infrequent dosing regimens. SA030 has a complementary and distinct mechanism from GLP-1 agonists and SGLT2 inhibitors, supporting its potential use in future combination regimens to reduce residual cardiometabolic risk not fully addressed by current therapies.

 

This marks GSK's second major move in the oligonucleotide field this year, following a deal with Frontier Biotech exceeding US$1 billion in February.

 

A day earlier, on May 5, Madrigal Pharmaceuticals and Arrowhead entered into an exclusive global license agreement for ARO-PNPLA3. ARO-PNPLA3 is a clinical-stage siRNA targeting patatin-like phospholipase domain-containing protein 3 (PNPLA3), a key genetic driver of MASH.

 

Under the agreement, Arrowhead receives a US25millionupfrontpayment,iseligibleforuptoUS25millionupfrontpayment,iseligibleforuptoUS975 million in additional payments upon achieving specific milestones, as well as tiered royalties on net sales.

 

Madrigal is the first company globally to successfully launch a marketed MASH drug, Rezdiffra (resmetirom). In February, Madrigal entered into a license agreement with Ribo Life Sciences to co-develop six innovative siRNA therapies for MASH based on Ribo's liver-targeting RiboGalSTAR™ platform.

 

The ARO-PNPLA3 license adds to Madrigal's pipeline a precision medicine approach for high-risk MASH patients. PNPLA3 I148M is a well-established genetic factor in MASH progression, associated with increased liver fat, inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma.

 

As can be seen, when the global oligonucleotide industry achieves multi-dimensional breakthroughs, Chinese innovative drug companies are not absent; they are resonating with the global industry, demonstrating strong global competitiveness and accelerating their pace on multiple fronts, including technology and pipelines.

 

Furthermore, from the perspective of the therapeutic areas where these deals are focused, transactions are concentrated in chronic conditions such as metabolic diseases and MASH, which have large patient populations and clear commercialization pathways. This aligns well with China's advantages in clinical resources and development efficiency, making it easier to achieve differentiated competition.

 

References:

1. Novartis Q1 2026 Results, Investor presentation

2. Wave Life Sciences Reports First Quarter 2026 Financial Results and Provides Business Update

3. Frontiers in Cell and Gene Therapy, Q1 2026 Global Oligonucleotide Drug Revenues Top 13

4. TONACEA, The Upside of Oligonucleotide Drugs Is Opening Up

5. TONACEA, 2026: A Comprehensive "Breakout" for Oligonucleotides

6. Drug Times, Ruida® Approved in China, Nobel Prize Platform siRNA Successfully Enters Extremely High Triglyceride Disease Space First!