Last updated: October 30, 2025
Introduction
ONPATTRO (patisiran), developed by Alnylam Pharmaceuticals, represents a pioneering RNA interference (RNAi) therapeutic approved by the FDA in 2018 for the treatment of hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) with polyneuropathy. Its innovative mechanism, targeting TTR gene synthesis, positions ONPATTRO as a groundbreaking approach in rare disease therapeutics. This report offers a comprehensive review of recent clinical trial developments, evaluates market dynamics, and projects future growth trajectories for ONPATTRO.
Clinical Trials Update
Ongoing and Completed Clinical Trials
Since FDA approval, ONPATTRO has undergone extensive clinical evaluation, including trials focusing on different disease manifestations, alternative delivery methods, and broader patient populations.
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APOLLO Phase 3 Trial (NCT03181270): The landmark trial that led to FDA approval demonstrated significant improvements in neurological impairment and quality of life in patients with stage 1 or 2 hATTR amyloidosis with polyneuropathy. The trial involved 225 patients, randomized to receive either patisiran or placebo. Results showed a 56% reduction in serum TTR levels and meaningful neurological improvements within 18 months [1].
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APOLLO-B (NCT04524207): An open-label extension trial assessing long-term safety and efficacy. Preliminary data suggest durability of effect, with persistent TTR suppression and stabilization or improvement in neurological function over a period extending beyond six years.
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HELIOS-A (NCT04287163): An ongoing Phase 3 trial investigating patisiran in wild-type TTR amyloidosis (ATTRwt), a form affecting older adults without hereditary mutations. Results are anticipated to expand the drug’s indications.
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Other Trials: Multiple Phase 2 studies are underway exploring subcutaneous formulations, combination therapies, and alternative dosing schedules. Notably, Alnylam’s development pipeline includes a subcutaneous version of Patisiran ( vutrisiran), aiming to improve patient adherence and reduce treatment burden, currently in Phase 3 trials (HELIOS-A and HELIOS-B).
Emerging Data and Post-Approval Studies
Recent studies investigate outcomes beyond neuropathy, including cardiomyopathy associated with ATTR amyloidosis. The HELIOS-CM trial (NCT04639104), evaluating vutrisiran’s efficacy in cardiac amyloidosis, has demonstrated promising results, suggesting systemic benefits of RNAi therapy in amyloid burden reduction.
Market Analysis
Market Size and Segmentation
The global ATTR amyloidosis market remains niche but is experiencing rapid growth due to the therapeutic revolution driven by RNAi and antisense oligonucleotide technologies. The market size was valued at approximately USD 200 million in 2022 and is projected to reach USD 1.2 billion by 2030, growing at a CAGR exceeding 25%, according to MarketWatch estimates [2].
Key segments include:
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Hereditary TTR Amyloidosis (hATTR): The initial target population, with estimates suggesting approximately 50,000–100,000 patients worldwide, predominantly in the US, Europe, and India.
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Wild-Type TTR Amyloidosis (ATTRwt): Increasingly recognized, especially in older adults; accounts for an expanding subset.
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Cardiac and Neurological Subtypes: Patients with cardiomyopathy attributable to ATTR, constituting a substantial portion of the market. Cardiomyopathy alone may represent nearly 65% of the total TTR amyloidosis population.
Competitive Landscape
While ONPATTRO secured the first FDA approval, other therapies are emerging:
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Vutrisiran (Alnylam): An subcutaneous, second-generation RNAi therapeutic in advanced clinical trials, predicting improved administration convenience.
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Tafamidis (Vyndaqel, Pfizer): A TTR stabilizer approved for ATTR cardiomyopathy, representing a different treatment paradigm focusing on stabilization rather than TTR knockdown.
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Inotersen (Akcea/Ionis): An antisense oligonucleotide approved for hATTR amyloidosis with polyneuropathy, competing with patisiran on efficacy and safety profiles.
Despite this, ONPATTRO maintains leading market share owing to its proven efficacy, safety profile, and first-to-market advantage.
Pricing and Reimbursement
The wholesale acquisition cost (WAC) for ONPATTRO is approximately USD 450,000 annually, reflecting the complex manufacturing process and the rarity indication. Reimbursement negotiations have varied per country but generally involve leveraging its FDA approval and clinical efficacy advantages.
Market Penetration and Adoption Trends
In the US, the adoption rate remains steady, with an estimated 3,000–4,000 patients on therapy by the end of 2022. Limited awareness, diagnostic delays, and manufacturing constraints have tempered initial uptake. Nonetheless, ongoing physician education and expanded diagnosis are poised to accelerate growth.
Future Projections
Growth Drivers
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Expansion to ATTRwt and Cardiac Subtypes: The positive outcomes in ongoing trials like HELIOS-A and HELIOS-CM could facilitate label extensions beyond hereditary neuropathy.
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Introduction of Vutrisiran: Its subcutaneous administration affords improved patient convenience, likely boosting uptake and adherence.
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Enhanced Diagnostic Capabilities: Increased screening, especially in cardiac clinics, will identify more eligible patients, expanding the market.
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Pricing Strategies and Access: Market access negotiations, especially in Europe and Asia, could influence sales volume and revenue optimization.
Potential Challenges
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Emerging Total Market: Competition from small-molecule stabilizers like tafamidis and inotersen may limit market share.
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Cost and Reimbursement: High affordability barriers could restrain market penetration, particularly in developing nations.
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Safety and Long-term Data: Need for extended safety profiles might impact physician confidence and payer decisions.
Market Projection (2023–2030)
Based on current clinical trajectories and market dynamics, ONPATTRO’s global sales are expected to grow at a CAGR of approximately 20–30%. Revenues could reach USD 600 million by 2025 and potentially approach USD 1 billion by 2030, driven largely by expanded indications, increased diagnosis, and novel formulations.
Conclusion
ONPATTRO remains a pioneering RNAi therapy shaping the landscape of rare disease management. Its ongoing clinical development efforts, notably for ATTRwt and cardiomyopathic indications, promise substantial future growth. Parallel advances in formulation and delivery are poised to enhance patient adherence and widen access. However, intensifying competition and economic challenges necessitate continuous innovation and strategic positioning within an evolving therapeutic ecosystem.
Key Takeaways
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Clinical Innovation: ONPATTRO’s robust Phase 3 trial data underpin its current market standing; ongoing studies are exploring broader indications and formulations.
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Market Dynamics: The ATTR amyloidosis market is expanding rapidly, driven by unmet needs in systemic and cardiac manifestations, with projections favoring significant growth.
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Competitive Edge: First-mover advantages, proven efficacy, and emerging subcutaneous formulations position ONPATTRO favorably against competitors.
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Challenges and Risks: Pricing pressures, diagnostic delays, and competitive innovations could impact sustained growth.
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Strategic Outlook: To maximize market potential, stakeholders should focus on expanding indications, improving patient access, and advancing combination therapies.
FAQs
1. What differentiates ONPATTRO from other treatments for amyloidosis?
ONPATTRO employs RNA interference to reduce pathogenic TTR protein synthesis, addressing the root cause of hereditary and wild-type transthyretin amyloidosis, unlike stabilizers like tafamidis which prevent TTR aggregation.
2. Are there ongoing efforts to improve ONPATTRO’s delivery and dosing?
Yes. Vutrisiran, a subcutaneous formulation of RNAi therapy, in late-phase trials, aims to offer similar efficacy with better convenience, potentially enhancing adherence.
3. What are the main safety concerns associated with ONPATTRO?
Common adverse events include infusion-related reactions and flushing. Long-term safety data is favorable but ongoing post-market surveillance continues to monitor for rare adverse effects.
4. How significant is the potential market for ATTR amyloidosis treatments?
With an estimated 50,000–100,000 patients worldwide, and increasing recognition of ATTRwt, the market's potential is sizeable, especially as diagnosis rates improve.
5. What is the outlook for ONPATTRO’s market share amid competition?
While facing competition from other RNAi and stabilizer therapies, ONPATTRO’s established efficacy and ongoing expansion into new indications support continued market leadership, provided it maintains a favorable safety profile and access.
References
[1] Adams D, et al. Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis. N Engl J Med. 2018;379(1):11-21.
[2] MarketWatch. "Hereditary Transthyretin Amyloidosis Market Size, Share & Trends." 2022.
