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Achieved full-year GAAP profitability in 2025, a landmark transition driven by 81% year-over-year growth in net product revenues.<\/p>\n<\/li>\n
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The TTR franchise delivered $858 million in Q4, representing 151% growth year-over-year, primarily fueled by the U.S. launch of Amvuttra for ATTR cardiomyopathy.<\/p>\n<\/li>\n
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Amvuttra has approached parity with tafamidis in share of new treatment starts by its second full quarter post-launch, signaling a shift in prescribing dynamics.<\/p>\n<\/li>\n
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Launched Cyrillis, a proprietary enzymatic ligation-based manufacturing platform designed to expand capacity and reduce cost of goods for RNAi therapeutics.<\/p>\n<\/li>\n
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Management attributes commercial success to broad first-line payer access, with over 90% of payers providing coverage without step-through requirements.<\/p>\n<\/li>\n
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The Alnylam 2030 strategy aims for a 25% revenue CAGR and 30% non-GAAP operating margins, leveraging a pipeline of over 25 clinical programs.<\/p>\n<\/li>\n<\/ul>\n
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2026 TTR revenue guidance of $4.4 billion to $4.7 billion assumes continued brisk category growth and a mid-single-digit net price decrease in the U.S.<\/p>\n<\/li>\n
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Anticipate a Q1 2026 revenue headwind due to pricing alignment in Germany for the cardiomyopathy launch and annual U.S. insurance reauthorizations.<\/p>\n<\/li>\n
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Expect to share clinical de-risking data in the second half of 2026 for Huntington\u2019s disease (ALN-HTT02) and obesity (ACVR1C) programs.<\/p>\n<\/li>\n
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The 2030 roadmap includes launching nuceresiran, which lacks royalty obligations and is expected to drive operating margins toward the mid-40s post-2030.<\/p>\n<\/li>\n
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Planned R&D investment will remain at approximately 30% of revenues to accelerate organic innovation and selectively access external technologies.<\/p>\n<\/li>\n<\/ul>\n
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Gross margin on product sales decreased to 77% in 2025 due to higher royalty tiers payable to Sanofi as Amvuttra revenues scaled.<\/p>\n<\/li>\n
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International TTR revenue growth in 2026 is expected to be consistent with 2025, tempered by lower launch pricing for cardiomyopathy in European markets.<\/p>\n<\/li>\n
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Collaboration revenue is projected to decline 38% in 2026 because a one-time $300 million milestone from the zalesiran program will not recur.<\/p>\n<\/li>\n
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Management flagged potential near-term ‘choppiness’ in Q1 results due to fewer shipping weeks and seasonal insurance dynamics.<\/p>\n<\/li>\n<\/ul>\n
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Management believes they are well-positioned to manage future competition due to established first-line access and a 25% CAGR goal that already accounts for market entrants.<\/p>\n<\/li>\n
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Confirmed that value-based agreements have seen minimal utilization to date, supporting stable net pricing despite broader access.<\/p>\n<\/li>\n<\/ul><\/div>\n
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