Novartis’ Strategic siRNA Expansion: A Paradigm Shift in Cardiovascular Therapeutics

The pharmaceutical industry is witnessing a quiet revolution in cardiovascular therapeutics, driven by the emergence of RNA interference (RNAi) technology. Novartis, a global leader in innovation, has positioned itself at the forefront of this transformation through a series of strategic partnerships and pipeline advancements in small interfering RNA (siRNA) therapies. For investors, the question is no longer whether RNAi can reshape disease management but how Novartis’ aggressive bets on this platform will translate into long-term value creation.

Strategic Collaborations: A Financial and Technological Bet

Novartis’ recent partnerships underscore its commitment to RNAi. In June 2024, the company inked a four-year deal with ProFound Therapeutics, a biotech firm specializing in protein detection platforms, with an upfront payment of $25 million and potential milestone payments of up to $750 million per target for cardiovascular applications [1]. This was followed by a deeper collaboration with Argo Biopharma, a Chinese siRNA pioneer, in January 2024, featuring an initial $185 million upfront payment and up to $4.165 billion in milestones [2]. By September 2025, Novartis had expanded this partnership further, committing $160 million upfront and up to $5.2 billion in total for multiple siRNA candidates targeting cardiovascular diseases [3].

These financial commitments are not mere gestures. They reflect a calculated strategy to leverage cutting-edge RNAi platforms to address unmet needs in cardiovascular care. Unlike traditional small-molecule drugs, siRNA therapies offer the potential for long-lasting efficacy with infrequent dosing, a critical advantage in chronic conditions like hypercholesterolemia and lipoprotein(a) elevation.

Pipeline Progress: From Promising Candidates to Market Leadership

Novartis’ cardiovascular siRNA pipeline is anchored by two flagship candidates: inclisiran (Leqvio) and pelacarsen (TQJ230). Inclisiran, already approved in several markets, reduces LDL cholesterol by ~50% with twice-yearly dosing, addressing adherence challenges in lipid management [4]. Pelacarsen, in Phase 3 trials (Lp(a) HORIZON), targets lipoprotein(a), an unmodifiable risk factor for cardiovascular disease [5]. If successful, these therapies could redefine standards of care, particularly for patients with genetic predispositions to cardiovascular risks.

The company’s pipeline also includes early-stage assets like CYX082 (fabursen), an siRNA targeting autosomal dominant polycystic kidney disease, and a broader push to establish U.S. manufacturing for siRNA technologies [6]. These efforts align with Novartis’ ambition to dominate the next frontier of cardiovascular therapeutics.

Market Dynamics: Growth, Challenges, and Regulatory Tailwinds

The RNAi-based cardiovascular therapeutics market is poised for robust growth. According to market forecasts, the global RNAi therapeutics market is expected to expand from $1.8 billion in 2024 to $3.3 billion by 2033, with a compound annual growth rate (CAGR) of 7.03% [7]. Cardiovascular applications, including metabolic disorders and rare diseases like primary hyperoxaluria, are key drivers. Regulatory incentives, such as orphan drug designations and fast-track approvals, further accelerate development timelines [8].

However, challenges persist. High development costs and delivery complexities—such as ensuring siRNA molecules reach target tissues without off-site effects—remain hurdles. Novartis’ partnerships with biotechs like Argo Biopharma, which specialize in advanced lipid nanoparticle delivery systems, mitigate these risks by pooling expertise and resources [9].

Long-Term Value Creation: A Calculated Risk?

For investors, Novartis’ RNAi strategy represents a high-stakes bet with potentially outsized rewards. The company’s financial discipline—evidenced by its $23 billion investment in U.S. manufacturing and R&D over five years [10]—suggests a long-term vision. CEO Vasant Narasimhan has emphasized the importance of “transformative” therapies in driving growth, with pelacarsen’s Phase 3 results in 2025 a pivotal milestone [11].

The broader market context also favors Novartis. With global cardiovascular disease affecting over 500 million people and rising healthcare costs pushing demand for cost-effective treatments, siRNA therapies could capture significant market share. Inclisiran’s commercial success—projected to generate $3 billion in annual sales by 2027—already demonstrates the commercial viability of RNAi in this space [12].

Conclusion: A Strategic Imperative

Novartis’ foray into siRNA is more than a scientific breakthrough; it is a strategic imperative to maintain relevance in an era of personalized medicine. By combining financial muscle with biotech agility, the company is addressing both the technical and commercial challenges of RNAi. While risks remain, the potential to redefine cardiovascular care—and capture a growing market—makes this expansion a compelling investment case.

Source:
[1] Novartis returns to Argo-multi-faceted $5B cardiovascular collab [https://www.fiercebiotech.com/biotech/novartis-returns-argo-multi-faceted-5b-cardiovascular-collab]
[2] Novartis Doubles Down on Argo Pact With Fresh $5.2B ... [https://www.biospace.com/business/novartis-spending-spree-continues-with-5-2b-argo-sirna-pact]
[3] Novartis pens $5.2bn cardiovascular partnership with Argo [https://pharmaphorum.com/news/novartis-pens-52bn-cardiovascular-partnership-argo]
[4] RNA gene therapies offer hope for millions with high ... [https://www.nature.com/articles/d41591-025-00002-2]
[5] Novartis R&D, Pipeline, and Clinical Trials [https://note.com/montepanquieu/n/na9e9e3a28b3b]
[6] Novartis plans to expand its US-based manufacturing and ... [https://www.novartis.com/us-en/news/media-releases/novartis-plans-expand-its-us-based-manufacturing-and-rd-footprint-total-investment-23b-over-next-5-years]
[7] Antisense & RNAi Therapeutics Market Outlook 2025-2033 [https://uk.finance.yahoo.com/news/antisense-rnai-therapeutics-market-outlook-080200235.html]
[8] RNAi Drugs in Emerging Markets: Analysis and Projections [https://www.datainsightsmarket.com/reports/rnai-drugs-1180293]
[9] RNAi Therapeutics Market Size Leads 14.9% CAGR by 2034 [https://www.towardshealthcare.com/insights/rnai-therapeutics-market-sizing]
[10] Novartis Annual Report 2024 | PDF [https://www.scribd.com/document/851839351/Novartis-Annual-Report-2024]
[11] 2024 Q2 results presentation and transcript [https://www.novartis.com/investors/financial-data/quarterly-results/2024-q2-transcript]
[12] age1's 2025 1st Annual Pharma Aging Report Card [https://www.librariesforthefuture.bio/p/age1s-2025-1st-annual-pharma-aging]