Financial Data and Key Metrics Changes - Alnylam Pharmaceuticals reported total net product revenues of $851 million for Q3 2025, representing a 103% year-over-year growth [8][26] - The TTR franchise revenues reached $724 million, reflecting a 135% increase year-over-year, driven primarily by the AMVUTTRA® ATTR-CM launch in the U.S. [7][10] - The company increased its total net product revenue guidance for 2025 from a range of $2.65 billion-$2.8 billion to $2.95 billion-$3.05 billion, marking a 10% increase at the midpoint [8][30] Business Line Data and Key Metrics Changes - The rare disease portfolio achieved $127 million in sales, up 14% compared to Q3 2024, indicating steady performance despite a focus on TTR growth [9][10] - U.S. net sales for the TTR franchise grew 42% quarter-over-quarter and 194% year-over-year, reflecting strong adoption following the AMVUTTRA® ATTR-CM label expansion [10][11] - International revenues grew 13% quarter-over-quarter and 46% year-over-year, highlighting continued global momentum [11][12] Market Data and Key Metrics Changes - The U.S. TTR franchise generated $543 million in net product revenues, with patient demand roughly doubling compared to Q2 [14][15] - The company anticipates further international AMVUTTRA® ATTR-CM launches in 2026, following local pricing and reimbursement reviews [11][16] - The hereditary ATTR polyneuropathy legacy business remains robust despite new competition, with a 46% year-over-year growth in ex-U.S. TTR markets [12][58] Company Strategy and Development Direction - Alnylam focuses on three core pillars: TTR leadership, growth through innovation, and strong financial performance [5][6] - The company is advancing its pipeline of RNAi therapeutics, with two new phase III trials underway and additional programs in development for various conditions [8][20] - The company aims to establish long-term leadership in TTR and expand its global reach through upcoming product launches [16][58] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the AMVUTTRA® ATTR-CM launch, highlighting strong execution and a solid foundation for future growth [9][10] - The management team noted that the majority of ex-U.S. launches are expected to begin in 2026, which will extend global reach and contribute to launch momentum [16][58] - The company remains optimistic about the potential of RNAi therapeutics to become the standard of care in TTR amyloidosis [18][19] Other Important Information - The gross margin on product sales was 77% for Q3 2025, down from 80% in Q3 2024, primarily due to increased royalties on AMVUTTRA® [27] - The company ended the quarter with cash, cash equivalents, and marketable securities of $2.7 billion, reflecting a stable financial position [29] Q&A Session Summary Question: AMVUTTRA® momentum in first line vs switch population - Management noted strong momentum in TTR business with patient demand doubling for AMVUTTRA® and broad adoption across various settings [35][36] Question: Confidence in continued patient additions for AMVUTTRA® - Management indicated that the guidance has been raised twice, reflecting confidence in the depth and durability of the product's momentum [39][41] Question: Payer dynamics and feedback - Management reported no payer headwinds and positive feedback from payers regarding the value of AMVUTTRA® [46][48] Question: Inventory demand and expectations for Europe - Management explained that inventory dynamics were stable, with modest contributions expected from ex-U.S. markets in Q4 [53][56] Question: Price changes for AMVUTTRA® in the U.S. and Europe - Management anticipates a gradual decline in net price over time, with ongoing negotiations for European pricing [72][73]