The "Breakthrough Moment" for Small Nucleic Acid Drugs

Ask AI · Why has GalNAc technology become a key breakthrough in small nucleic acid delivery?

The hype around small nucleic acid drugs continues to soar. Since 2026, the global spotlight in the biopharmaceutical sector has once again turned to the small nucleic acid space, and a competitive race to reshape the industry landscape has already begun.

Sanofi’s lipid-lowering siRNA drug, Pluslciran sodium injection, has been approved in China; RiboBio has listed on the Hong Kong Stock Exchange to raise over HK$1.8 billion; YaoJing Biotech has released the world’s first heart-targeted delivery platform; and China Biopharmaceutical has acquired Hejia Biotech for RMB 1.2 billion…

After decades of technical iteration and accumulation, small nucleic acid technologies are now in the peak, high-heat stage of an industry boom.

01

Clear commercialization results

So far, more than 20 small nucleic acid drugs have been approved for marketing worldwide, including ASO drugs, siRNA drugs, and nucleic-acid aptamer drugs. They cover multiple therapeutic areas such as rare diseases, cardiovascular diseases, and infectious diseases. The global R&D and commercialization progress of small nucleic acid drugs, led by overseas companies and accumulated over many years, has now entered a comprehensive harvest phase.

Alnylam is a leading company in the global small nucleic acid drug sector. With its leading siRNA technology platform, it has already formed a lineup of multiple commercial products up to now, covering multiple therapeutic areas including rare diseases, cardiovascular disease, and metabolism. In 2018, Alnylam’s Patisiran was approved for marketing, becoming the world’s first siRNA drug used to treat hereditary transthyretin (hATTR) familial amyloid polyneuropathy. Subsequently, products such as Lumasiran, Givosiran, Inclisiran, and Vutrisiran were approved one after another.

In fiscal year 2025, four independently commercialized siRNA products under Alnylam together generated revenue of $2.99B, a substantial increase of 81% year over year. Among them, flagship product Amvuttra (generic name Vutrisiran) was especially outstanding, with full-year revenue reaching $2.31B, and the year-over-year growth rate soaring to 138%. Notably, after successfully winning the ATTR-CM indication, Amvuttra saw explosive growth in sales; its annual sales surpassed $2 billion, successfully placing it among the category of “super blockbuster” drugs.

Benefiting from the strong growth momentum in 2025, Alnylam provided a more positive and optimistic performance outlook for 2026. According to the company’s guidance, full-year product sales in 2026 are expected to reach $4.9 billion to $5.3 billion, among which revenue guidance for the TTR product line has been significantly raised, projected to achieve $4.4 billion to $4.7 billion.

Besides Alnylam, Ionis, as a leading company in the ASO drug field, has also achieved remarkable commercialization results. The most successful commercialization case is Spinraza (Nusinersen), developed in collaboration with Biogen. Nusinersen was approved for marketing in 2016 to treat spinal muscular atrophy (SMA). The drug is the world’s first small nucleic acid drug for SMA. In 2025, Nusinersen’s sales were $1.55B. Tryngolza (olezarsen) was approved by the FDA in December 2024, becoming the first therapy for adult familial chylomicronemia syndrome (FCS to be approved by the FDA. Tryngolza generated $108 million in revenue in its first year on the market.

Sarepta focuses on muscle diseases, especially Duchenne muscular dystrophy (DMD). To date, the company has successfully developed and commercialized four DMD treatment drugs. Among them, Exondys 51 achieved sales of $538 million in 2025.

The entry of multinational pharma companies has further accelerated the commercialization of small nucleic acid drugs. Novartis, through its collaboration with Alnylam, obtained global commercialization rights for the siRNA drug Leqvio (Inclisiran sodium injection). Leveraging the convenience of “once every six months” dosing, the drug quickly gained market recognition. Its sales reached $112 million in 2022, $355 million in March 2023, and $754 million in July 2024. By 2025, it successfully surpassed $1 billion, showing an accelerated uptake trend and becoming the first small nucleic acid drug in the chronic-disease category to achieve large-scale commercialization.

The commercialization success of global small nucleic acid drugs is reflected not only in sales, but also in capital market recognition. In 2025, driven by factors such as RNAi therapy Amvuttra’s sales performance far exceeding expectations, Alnylam’s stock price rose strongly. Small nucleic acid listed companies such as Ionis and Avidity also performed steadily.

02

Expansion from rare diseases to chronic diseases

In early small nucleic acid drug R&D, the field chose rare genetic diseases with clearly identified disease-causing genes and urgent unmet medical needs. These diseases are typically caused by defects in a single gene, providing an ideal scenario for precise one-to-one intervention with small nucleic acid drugs. At the same time, policy benefits for rare-disease drugs—such as orphan drug designation—can accelerate the approval process, enabling companies to quickly validate their technology platforms.

Nusinersen is the first ASO drug worldwide for treating spinal muscular atrophy (SMA). By modulating the splicing of the SMN2 gene, it increases the expression of functional SMN protein, changing the treatment landscape for this fatal inherited disease and setting a sales record at the same time.

These successes in the rare-disease space have not only brought patients new hope, but also completed initial validation of small nucleic acid drug mechanisms of action, safety, and the production system, laying a solid scientific and industrial foundation for subsequent expansion.

The biggest bottleneck in expanding small nucleic acid drugs into common diseases lies in delivery. How can fragile macromolecular nucleic acids be safely and efficiently delivered to target tissue cells? The breakthrough solution to this challenge began with the maturation and application of the N-acetylgalactosamine (GalNAc) conjugation technology. GalNAc can specifically bind to the ASGPR receptors highly expressed on the surface of liver cells, enabling efficient, precise liver-targeted delivery of siRNA. The significance of this turning point is profound: it turns the body’s metabolic hub—the liver—into the first common-disease battleground that small nucleic acid drugs can systematically conquer.

Success in liver-targeted delivery directly led to a series of major drugs targeting the cardiovascular metabolism area. In 2019, the first GalNAc-siRNA drug, Givosiran, was approved by the FDA for marketing. In December 2023, the first GalNAc-ASO drug, Eplontersen, was approved by the FDA for marketing.

Powered by GalNAc technology, small nucleic acid drugs quickly emerged in cardiovascular metabolism, the largest chronic-disease market. Its core advantage—“long-acting” effects—has been fully realized.

Inclisiran is one of the brightest stars in this space. It is the first siRNA drug targeting a common chronic condition (hypercholesterolemia), targeting the PCSK9 gene. Only two subcutaneous injections are needed per year, delivering potent reductions in low-density lipoprotein cholesterol (LDL-C). This broke the traditional pattern of taking medication daily or injecting antibodies once every two weeks, enabling a paradigm shift to an ultra-long-acting model for chronic-disease management. Since its launch, sales have continued to surge; in 2025, revenue reached $1.2B, and it is expected to become a new blockbuster.

For hypertriglyceridemia, siRNA drug Pelacarsen (annual dosing four times) targeting APOC3 and the ASO drug Olezarsen have also entered the scene, demonstrating exploration of different technology routes under the same target.

In other chronic-disease areas, small nucleic acid drugs have also achieved important breakthroughs. Finteplarsen, the world’s first siRNA therapy for hemophilia, reconstructs coagulation balance by lowering antithrombin levels; it requires only 6 injections per year, significantly reducing the burden on patients. Eplontersen, the ASO drug for treating hereditary transthyretin (hATTR) amyloid polyneuropathy, allows patients to self-administer once per month, significantly improving treatment experience.

Drug pipelines targeting lipoprotein(a) [Lp(a)], blood pressure lowering siRNA targeting angiotensinogen (AGT), and anticoagulant siRNA targeting factor XI (FXI), among others, are all advancing rapidly, aiming to provide more durable and more convenient treatment options.

Small nucleic acid drugs targeting key complement pathway factors (such as C5 and MASP-2) are expected to provide transformative therapies for conditions such as IgA nephropathy and paroxysmal nocturnal hemoglobinuria (PNH). FrontierBio has built MASP-2/CFB dual-target siRNA in this field.

The future ceiling depends on delivery beyond the liver, especially breakthroughs in central nervous system delivery technology. Novartis is strengthening its focus on neuromuscular diseases through the acquisition of Avidity, while companies such as Arrowhead are working to overcome the blood–brain barrier and exploring treatments for Parkinson’s disease, Alzheimer’s disease, and more. YaoJing Biotech’s release of the world’s first heart-targeted delivery platform, “Kardia Shuttle,” represents an innovative frontline attempt by a Chinese company to break through limitations outside the liver.

03

Global competition

Overseas leading companies occupy a dominant position in the industry by leveraging their technology accumulation and pipeline layout, and each has its own characteristics. In addition to the aforementioned three giants—Alnylam, Ionis, and Sarepta—other companies are also actively planning.

Arrowhead’s first commercial product, Redemplo, was approved as a major breakthrough, and its in-development pipeline covers multiple disease areas. In January 2026, Arrowhead disclosed clinical data for two siRNA obesity candidate drugs: ARO-INHBE and a combination of ARO-INHBE with tirzepatide. In patients with type 2 diabetes obesity, they achieved a 9.4% body weight reduction at week 16—about 2 times higher than tirzepatide alone.

When the global small nucleic acid industry achieves multidimensional breakthroughs, Chinese innovative drug companies are also not absent. They resonate in pace with the global industry, demonstrating strong global competitiveness and accelerating the race across multiple areas including technology, pipelines, and capital cooperation.

Humbvision Pharmaceuticals reached two major deals with Novartis in January 2024 and September 2025. The total value of the two collaboration transactions exceeded $9 billion, becoming a benchmark for international cooperation in China’s siRNA field. RiboBio reached a collaboration worth more than $2 billion with Boehringer Ingelheim in January 2024 for MASH drugs; in February 2026, it also signed a global exclusive licensing agreement with Madrigal Pharmaceuticals. Shengjins Biotech reached collaborations with Eli Lilly and Roche in November 2025 and February 2026, respectively. FrontierBio signed an agreement with GSK in February 2026, authorizing two siRNA pipelines with an upfront payment of $40 million. Jingyin Pharmaceutical entered into a collaboration with CRISPR Therapeutics.

In the capital markets, on January 9, 2026, RiboBio successfully listed on the Hong Kong Stock Exchange, raising more than HK$1.8 billion. The public offering was subscribed over 100 times. China Biopharmaceutical, a leading company on the Hong Kong market, acquired Hejia Biotech for RMB 1.2 billion in January 2026 in a wholly owned transaction, striking the first shot for large-scale mergers and acquisitions in this domestic field.

In in-development pipeline planning, Chinese companies show differentiated starting points and synchronous expansion compared with overseas peers. Unlike overseas companies starting from rare diseases, domestic companies—leveraging their latecomer advantage—are “more bold” in directly entering major disease areas such as cardiovascular disease and hepatitis B. By early 2026, domestic small nucleic acid pipelines under development had grown rapidly, with an increasingly rich range of pipelines reaching Phase II clinical trials and beyond. Indications are highly concentrated in major diseases such as cardiovascular metabolism and liver diseases, with targets covering PCSK9, ANGPTL3, HBV, and more. In recent years, they have also begun to rapidly expand into cutting-edge areas such as weight loss, CNS (central nervous system), and kidney diseases.

04

Conclusion

As third-generation therapeutic drugs, small nucleic acid drugs—with advantages such as high specificity and long-acting effects—are reshaping the global pharmaceutical industry at an unprecedented speed and intensity. In this wave, China’s strength is gradually moving from followers to co-runners, and even becoming a leader in certain fields. The era of small nucleic acid drugs is here—and it has only just begun.

References:

1. Company official websites

2. Cinda Securities

Image source: Xpress photo

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