Introduction
Patisiran sodium, marketed under the brand name Onpattro, is a revolutionary RNA interference (RNAi) therapy developed by Alnylam Pharmaceuticals for the treatment of hereditary transthyretin-mediated (hATTR) amyloidosis. This article delves into the market dynamics and financial trajectory of patisiran, highlighting its clinical significance, cost-effectiveness, and financial performance.
Clinical Significance of Patisiran
Patisiran specifically targets the 3’ untranslated region of all variant and wild-type TTR mRNA, leading to the catalytic degradation of TTR mRNA in the liver and a significant reduction in serum TTR protein levels. This mechanism results in an approximately 80% reduction in mean serum TTR within 10 to 14 days after a single dose, with sustained reductions of up to 84% after 18 months of treatment[4].
Market Demand and Patient Need
The demand for effective treatments for hATTR amyloidosis is high due to the severe and progressive nature of the disease. Patisiran offers significant clinical benefits, including improved quality of life and reduced disease progression, making it a critical option for patients with this rare genetic disorder.
Cost-Effectiveness and Pricing
The cost-effectiveness of patisiran is a contentious issue. Economic analyses by the Institute for Clinical and Economic Review (ICER) and the CADTH Common Drug Review indicate that, at its current list price of $345,000, patisiran far exceeds commonly accepted cost-effectiveness thresholds of $50,000 to $150,000 per quality-adjusted life year (QALY)[1][3].
To align with these thresholds, ICER suggests that the list price of patisiran would need to be discounted by 90% to 95%. Similarly, CADTH found that a price reduction of 98% would be required for patisiran to be cost-effective compared to best supportive care (BSC) at a willingness-to-pay threshold of $50,000 per QALY[1][3].
Financial Performance of Alnylam Pharmaceuticals
Alnylam Pharmaceuticals has seen significant growth in net product revenues driven by the success of Onpattro and its newer counterpart, AMVUTTRA (vutrisiran).
Quarterly and Annual Revenues
In the second quarter of 2023, Alnylam reported global net product revenues for Onpattro and AMVUTTRA of $91 million and $132 million, respectively, representing a 46% year-over-year growth in total TTR revenues compared to Q2 2022. This growth is particularly notable in the U.S. market, where total TTR revenues grew by 72% compared to the same period in 2022[5].
For the full year 2023, Alnylam reported total net product revenues of $1,241 million, with Onpattro and AMVUTTRA contributing significantly to this figure. The company also received substantial upfront payments from partnerships, such as $310 million from Roche for the co-development and co-commercialization of zilebesiran, which contributed to its financial stability[2].
Operating Costs and Expenses
Despite the revenue growth, Alnylam has incurred significant operating costs. In the second quarter of 2023, the company reported a GAAP operating loss of $229.8 million and a non-GAAP operating loss of $154 million. These losses are attributed to high research and development expenses, selling, general, and administrative costs, and increased costs of goods sold due to royalties and inventory impairments related to Onpattro[5].
Cost of Goods Sold
The cost of goods sold as a percentage of net product revenues increased in 2023, primarily due to higher royalties payable on net sales of AMVUTTRA and increased excess and obsolete charges related to the impairment of Onpattro inventory for which regulatory approval was not received[2].
Market Dynamics and Competition
The market for hATTR amyloidosis treatments is competitive, with other therapies like inotersen also available. However, patisiran has demonstrated dominance over inotersen in various scenario analyses, showing better cost-utility ratios and clinical outcomes[1].
Regulatory and Policy Environment
The regulatory and policy environment plays a crucial role in the market dynamics of patisiran. Discussions with policy roundtables and regulatory bodies aim to find solutions to ensure patient access despite the high costs. ICER’s public meetings and reports have highlighted the need for price adjustments to align with cost-effectiveness thresholds[3].
Future Outlook
Alnylam Pharmaceuticals is committed to continued innovation and expansion. The company has reiterated its 2023 financial guidance, expecting combined net product revenues between $1,200 million and $1,285 million. The strategic collaboration with Roche and other partnerships are expected to drive future growth and financial stability[5].
Key Challenges
Despite the clinical and commercial success, patisiran faces significant challenges, particularly related to its high cost and the need for substantial price reductions to achieve cost-effectiveness. Addressing these challenges through pricing strategies, discounts, and policy changes will be crucial for maintaining market viability.
Key Takeaways
- Clinical Efficacy: Patisiran offers significant clinical benefits for patients with hATTR amyloidosis.
- Cost-Effectiveness: The current pricing of patisiran exceeds commonly accepted cost-effectiveness thresholds, necessitating substantial price reductions.
- Financial Performance: Alnylam Pharmaceuticals has seen growth in net product revenues, but faces high operating costs.
- Market Dynamics: The market is competitive, with ongoing discussions to ensure patient access despite high costs.
- Future Outlook: Continued innovation and strategic partnerships are expected to drive future growth.
FAQs
What is patisiran sodium used for?
Patisiran sodium, marketed as Onpattro, is used for the treatment of hereditary transthyretin-mediated (hATTR) amyloidosis, a rare genetic disorder.
How does patisiran work?
Patisiran works through RNA interference (RNAi), causing the catalytic degradation of TTR mRNA in the liver, which reduces serum TTR protein levels.
Why is patisiran considered expensive?
Patisiran is considered expensive because its current list price far exceeds commonly accepted cost-effectiveness thresholds, requiring significant discounts to align with these thresholds.
What are the financial highlights for Alnylam Pharmaceuticals in 2023?
Alnylam reported global net product revenues of $1,241 million in 2023, with significant growth driven by Onpattro and AMVUTTRA. The company also received substantial upfront payments from partnerships.
What are the key challenges facing patisiran in the market?
The key challenges include the high cost of the drug, the need for substantial price reductions to achieve cost-effectiveness, and ensuring patient access through policy and pricing strategies.
Sources
- CADTH Common Drug Review Pharmacoeconomic Review Report for Onpattro
- Alnylam Pharmaceuticals Reports Fourth Quarter and Full Year 2023 Financial Results
- Institute for Clinical and Economic Review Finds Current List Price of Patisiran Far Exceeds Cost-Effectiveness Thresholds
- European Medicines Agency - ONPATTRO, INN-patisiran
- Alnylam Pharmaceuticals Reports Second Quarter 2023 Financial Results
