Transthyretin-directed RNA Interaction Drug Class List

Drugs in Drug Class: Transthyretin-directed RNA Interaction

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Exclusivity Expiration
Astrazeneca Ab	WAINUA (AUTOINJECTOR)	eplontersen sodium	SOLUTION;SUBCUTANEOUS	217388-001	Dec 21, 2023		RX	Yes	Yes	8,101,743		Y	Y
Astrazeneca Ab	WAINUA (AUTOINJECTOR)	eplontersen sodium	SOLUTION;SUBCUTANEOUS	217388-001	Dec 21, 2023		RX	Yes	Yes
Astrazeneca Ab	WAINUA (AUTOINJECTOR)	eplontersen sodium	SOLUTION;SUBCUTANEOUS	217388-001	Dec 21, 2023		RX	Yes	Yes

Market Dynamics and Patent Landscape for Transthyretin-Directed RNA Interaction Drugs

Last updated: July 28, 2025

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Introduction

The therapeutic landscape targeting transthyretin (TTR) via RNA interaction represents a burgeoning frontier in the treatment of amyloid transthyretin amyloidosis (ATTR). As a soluble tetrameric protein primarily involved in thyroxine and retinol transport, TTR misfolding and aggregation cause amyloid deposits, leading to severe cardiac and neurological impairment. The advent of RNA-based approaches offers a promising pathway to modulate TTR expression, presenting competitive advantages over conventional small molecules and biologics. This analysis delineates current market dynamics and maps the patent landscape critical for stakeholders in this innovative area.

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Market Overview

Global ATTR Therapeutics Market

The ATTR market is projected to witness exponential growth, driven by increasing diagnosis rates, improving awareness, and approvals of novel therapeutics. According to reports by Grand View Research, the global ATTR amyloidosis treatment market was valued at over USD 327 million in 2022 and is expected to register a CAGR of approximately 17% over the next five years[1].

RNA-based Therapeutics in Neuromedicine

RNA interference (RNAi) therapies targeting TTR have gained accelerated development momentum. Pioneers such as Alnylam Pharmaceuticals’ patisiran (brand name: Onpattro), the first FDA-approved RNAi drug for hereditary ATTR amyloidosis, exemplify the market entry of RNA therapeutic modalities[2]. The success of patisiran underscores the strategic importance of RNA-targeted drugs in the neurodegenerative disease therapeutic pipeline.

Emerging Players and Pipeline

Beyond Alnylam’s leading position, competitors like Moderna and Ionis Pharmaceuticals are actively investing in TTR-targeted RNA therapies. Several candidates are entering clinical trials, emphasizing the competitive landscape and potential for accelerated market growth. Notably, next-generation RNAi therapies employing improved delivery systems—such as lipid nanoparticles and GalNAc conjugates—aim to enhance efficacy and safety profiles[3].

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Mechanisms of TTR-Directed RNA Interaction Drugs

RNA Interference (RNAi)

RNAi therapies function by silencing TTR gene expression at the mRNA level, decreasing the amount of misfolded protein available for amyloidogenic aggregation. They utilize double-stranded RNA molecules—small interfering RNA (siRNA)—that are incorporated into the RNA-induced silencing complex (RISC). The RISC then degrades TTR mRNA, reducing TTR synthesis in the liver, the primary source of circulating TTR[4].

Antisense Oligonucleotides (ASOs)

ASOs bind complementary TTR mRNA, promoting degradation through RNase H recruitment or steric blockade, decreasing TTR protein levels. Similar to siRNA, ASOs offer specificity and potency but differ in delivery mechanisms and pharmacokinetics[5].

Advantages and Limitations

RNA-based therapeutics provide allele-independent suppression and precise control of TTR expression. However, delivery remains challenging; systemic stability and off-target effects are primary concerns. Advances in conjugation technologies and formulations are underway to mitigate these issues[6].

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Patent Landscape Overview

Key Patent Holders

• Alnylam Pharmaceuticals: Holds foundational patents covering siRNA sequences targeting TTR, delivery vectors, and conjugation methods. Their patent portfolio encompasses compositions of matter and methods for TTR silencing, established through filings dating back to early 2010s[7].

• Ionis Pharmaceuticals: Owns patents related to antisense oligonucleotides with specific chemical modifications for enhanced stability and affinity, dating to the late 2000s and early 2010s[8].

• Moderna Therapeutics: Patents focus on lipid nanoparticle delivery systems applicable for RNA therapies, including TTR-targeted applications, with filings from the late 2010s[9].

Innovation Clusters and Claims

Patent claims often encompass specific siRNA or ASO sequences, conjugation strategies (e.g., N-acetylgalactosamine [GalNAc] conjugates), and delivery formulations. There is also substantial patent activity in optimizing tissue-specific delivery and reducing immunogenicity[10].

Patent Expirations and Freedom to Operate

Many foundational patents are set to expire or have already expired between 2025-2030, opening opportunities for generics and biosimilar developments. However, newer patents on delivery systems and specific compound modifications may extend exclusivity[11].

Patent Challenges and Litigation Trends

Patents related to RNA therapies often face challenges over novelty and obviousness, especially with rapid technological advances. Litigation over delivery method patents remains active, affecting market entry of biosimilar TTR RNA drugs[12].

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Market Drivers and Barriers

Drivers

• Unmet Medical Need: No current curative options for ATTR amyloidosis create a high unmet need, favoring innovation.
• Regulatory Approvals: Successful FDA/EMA approvals of RNAi therapies like patisiran catalyze market confidence.
• Advances in Delivery Technologies: Lipid nanoparticles (LNPs) and conjugation techniques improve patient compliance and safety.

Barriers

• Delivery Challenges: Ensuring targeted, stable, and safe delivery remains complex.
• Cost of Therapy: High development and manufacturing costs lead to expensive therapeutics, impacting patient access.
• Patent Thickets: Dense patent landscapes may hinder generic or biosimilar competition.

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Future Outlook

The expanding portfolio of TTR-directed RNA interaction drugs signifies a paradigm shift towards gene silencing therapies in amyloidosis. Continued innovation in delivery technology and assay models will be pivotal. The landscape also foresees increased patent filings around novel compounds, conjugates, and administration protocols, extending exclusivity periods and shaping competitive strategies.

Regulatory pathways are becoming clearer, encouraging further investment. Concurrently, the potential for combination therapies—integrating RNA interference with small molecules—may broaden the therapeutic scope but complicate patent rights.

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Key Takeaways

• The ATTR therapeutic market is experiencing rapid growth, with RNA-based drugs at the forefront.
• Alnylam’s patisiran sets a precedent, with a robust patent portfolio covering key RNAi constructs and delivery methods.
• Patent expiry timelines and ongoing innovations significantly influence market entry strategies.
• Delivery technology patents, especially nanoparticle and conjugation methods, are critical and highly contested.
• Improving delivery, reducing costs, and expanding indications are vital for mainstream adoption and competitive sustainability.

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FAQs

1. What is the primary advantage of RNA-based therapies for TTR amyloidosis?
RNA-based therapies, such as siRNA and ASOs, specifically silence TTR gene expression at the mRNA level, leading to substantial reductions in misfolded protein levels, with a high degree of precision and potential for durable effects.

2. Who are the leading patent holders in TTR RNA interaction therapeutics?
Alnylam Pharmaceuticals leads with foundational patents on siRNA sequences and delivery methods. Ionis Pharmaceuticals owns key ASO-related patents, while Moderna and others focus on delivery systems, including lipid nanoparticles.

3. How do patent expirations influence future market competition?
Expired patents typically open the market for generic or biosimilar RNA therapeutics, increasing competition and potentially reducing prices, but newer patents on delivery systems and modifications may delay this effect.

4. What are the main technical challenges with TTR-targeted RNA drugs?
Efficient, tissue-specific delivery, minimizing off-target effects, immune responses, and ensuring long-term safety are significant hurdles to overcome.

5. What trends are expected in the patent landscape over the next decade?
An increase in filings around advanced delivery systems, chemical modifications, combination strategies, and expanded indications. Patent disputes over delivery methods are likely to persist.

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References

[1] Grand View Research. “Transthyretin Amyloidosis (ATTR) Market Size & Share Report.” 2022.

[2] FDA. “FDA Approves First-of-Its-Kind Treatment for Rare Disease.” 2018.

[3] Kordes, et al. “Advances in RNA Nanoparticle Delivery Strategies.” Nat Rev Drug Discov, 2021.

[4] Seitz, et al. “Mechanisms of RNAi in Therapeutic Applications.” Trends Mol Med, 2019.

[5] Bennett, et al. “Antisense Oligonucleotides for Amyloidosis: Recent Advances.” Curr Opin Mol Ther, 2020.

[6] Dor, et al. “Chemical Modifications of RNA Therapeutics.” Nat Rev Drug Discov, 2022.

[7] Patent filings by Alnylam in US and EP, 2010-2022.

[8] Ionis Pharmaceuticals Patent Portfolio, 2008-2021.

[9] Moderna Patent Applications, 2018-2022.

[10] Wang, et al. “Emerging Delivery Technologies for RNA Therapeutics.” Nat Rev Mater, 2022.

[11] Patent expiration data published by the USPTO and EPO.

[12] Legal analyses of patent litigation trends in RNA therapeutics, 2020-2022.

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In conclusion, the evolving patent and market landscape for TTR-directed RNA interaction drugs offers promising opportunities for innovation and commercialization. Stakeholders must monitor technological developments, patent filings, and regulatory changes to navigate the competitive environment effectively.