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    ALNY
    Earnings call· Dec 2025(Q4 FY25)

    ALNYLAM PHARMACEUTICALS, INC. ALNY

    Feb 12, 2026 Source

    Executive summary

    Alnylam Pharmaceuticals Q4 FY25 — Landmark Year with GAAP Profitability and Strong AMVUTTRA Launch

    Alnylam Pharmaceuticals concluded a transformational Q4 FY25, achieving GAAP profitability for the full year and exceeding its P5x25 goals, driven by the successful launch of AMVUTTRA for ATTR cardiomyopathy. The company is now focused on its Alnylam 2030 goals, aiming for global TTR leadership, sustainable innovation with blockbuster potential medicines, and scaling with discipline to achieve over 25% revenue CAGR and 30% non-GAAP operating margin by 2030. Despite anticipated Q1 2026 revenue phasing impacts, management remains confident in the long-term growth trajectory of its TTR franchise and pipeline.

    Highlights

    5

    • Achieved nearly $3 billion in combined net product revenues in 2025, an 81% growth compared to 2024.

    • Delivered GAAP profitability for the full year 2025, meeting P5x25 goals.

    • AMVUTTRA for ATTR cardiomyopathy achieved strong early momentum, approaching parity with tafamidis in new treatment starts by Q2 post-launch.

    • Expanded clinical pipeline with 4 proprietary CTAs and 5 partner-led programs, ending 2025 with over 25 clinical programs.

    • Secured broad and durable access for AMVUTTRA, with over 90% of payers providing first-line coverage without step-through requirements for 2026.

    Concerns

    3

    • Expected modest near-term impact on total TTR revenue in Q1 2026 due to adjusted AMVUTTRA pricing in Germany, resulting in an approximate $25 million reduction in Q1 international revenues.

    • Anticipated lower quarter-over-quarter TTR revenue growth in Q1 2026 for the U.S. due to fewer product shipping weeks and the expected impact of annual insurance reauthorizations.

    • Forecasted mid-single-digit net price decrease for AMVUTTRA in 2026 in the U.S. market.

    Guidance & targets

    13
    CategoryTargetConfidence
    Combined Net Product Revenues
    $4.9 billion to $5.3 billion
    high materiality
    High
    Rare Franchise Net Product Revenues
    $500 million to $600 million
    medium materiality
    High
    TTR Franchise Net Product Revenues
    $4.4 billion to $4.7 billion
    high materiality
    High
    Collaboration and Royalty Revenue
    $400 million to $500 million
    medium materiality
    Medium
    Combined Non-GAAP R&D and SG&A Expense
    $2.7 billion and $2.8 billion
    high materiality
    High
    Nucresiran Launch
    2028
    high materiality
    Medium
    Nucresiran Launch
    2030
    high materiality
    Medium
    Revenue CAGR
    over 25%
    high materiality
    High
    Non-GAAP Operating Margin
    approximately 30%
    high materiality
    High
    Pipeline of Clinical Programs
    over 40
    medium materiality
    High
    RNAi Delivery to Tissue Types
    10
    medium materiality
    High
    Non-GAAP R&D Investment
    approximately 30% of revenues
    medium materiality
    High
    New INDs
    3 to 4
    low materiality
    High

    Segment performance

    4
    SegmentRevenueYoYQoQMargin
    Rare Disease Portfolio
    Driven by increased patient demand and favorable order timing in partner markets. Achieved $0.5 billion franchise status in 2025, reflecting continued growth more than 5 years post launch.
    GIVLAARI and OXLUMO combined 2025 revenue: $0.5 billion
    		$136 million26%——
    TTR Franchise
    Robust quarter, continuing strong launch trajectory. Primary growth engine for the company.
    		$858 million151%18%—
    TTR Franchise - U.S.
    Growth primarily driven by continued increase in U.S. patient demand, partially offset by increased gross-to-net deductions and unfavorable inventory channel impact.
    		—222%20%—
    TTR Franchise - International
    Underscores continued global momentum. Early signs in Japan CM launch are in line with leading analogs. Germany pricing adjustment for AMVUTTRA-CM will create modest near-term impact in Q1 2026.
    		—47%13%—

    Operational metrics

    17
    Combined Net Product Revenues
    $3 billion81% growth vs 2024
    FY25

    Achieved landmark approval of AMVUTTRA for ATTR cardiomyopathy and driven by the success of that launch.

    Combined Net Product Revenues
    $995 million121% growth year-over-year; 17% growth versus prior quarter
    Q4 FY25

    Q4 represented another quarter of strong growth for Alnylam.

    Collaboration Revenue
    $553 million8% growth compared with 2024
    FY25

    Included a $300 million development milestone in Q3 associated with the dosing of the first patient in ZENITH Phase III trial for zilebesiran.

    Royalty Revenue
    $174 million90% increase compared with last year
    FY25

    Driven by higher Leqvio sales from Novartis.

    Gross Margin on Product Sales
    77%4% decrease compared with 2024
    FY25
    Non-GAAP R&D Expenses
    $1.2 billionincreased 17% compared to last year
    FY25
    Non-GAAP SG&A Expenses
    $1 billionincreased 22% compared to last year
    FY25
    Non-GAAP Operating Income
    $850 millionrepresenting a $755 million increase compared with last year
    FY25

    Driven primarily by strong top-line results.

    Cash, Cash Equivalents and Marketable Securities
    $2.9 billioncompared with $2.7 billion at the end of 2024
    end of FY25
    AMVUTTRA Net Price Decrease
    mid-single-digitsimilar to 2025
    FY26

    Expected to be gradual over the course of the year.

    International TTR Revenue Reduction
    $25 million
    Q1 FY26

    Expected to cause considerably lower quarter-on-quarter TTR revenue growth in Q1.

    U.S. TTR Quarterly Growth
    more modestcompared with $111 million of U.S. quarterly growth achieved in Q4 FY25
    Q1 FY26

    Beyond Q1, higher quarterly growth is expected for the balance of the year in the U.S.

    TTR Category Volume CAGR
    40%
    past 6 years

    Despite this growth, the majority of patients with ATTR cardiomyopathy remain untreated.

    AMVUTTRA Payer Coverage - First-line
    over 90%versus last year
    2026

    Following completion of 2026 payer policy discussion, increased confidence in broader patient access.

    AMVUTTRA Patient Out-of-Pocket Costs
    0
    2026

    Supported by a broad, well-established network of sites of care.

    AMVUTTRA Patient Access to Treatment Sites
    90%
    2026

    Supported by a broad, well-established network of sites of care.

    Huntington's Protein Knockdown Target
    over 50%
    Phase I program

    Goal for ALN-HTT02 in Phase I program to achieve good levels of knockdown durably and safely.

    Industry KPIs

    7
    MetricValueDetails
    Launch access metricsover 90%%
    Pipeline read out calendarover 25programs
    Regulatory approvals filingsAMVUTTRA
    Therapeutic drug market shareapproached parity
    Prescription volume new startsshifting
    Collaboration milestone royalty revenue$727 millionUSD
    Cumulative patients uptake since launchhundreds of thousandspatients

    Product announcements

    1
    ProductTypeDetails
    siRELISlaunch

    Deals & partnerships

    3
    RocheCollaboration for zilebesiran$300 million

    This milestone will not recur in 2026, impacting collaboration revenue guidance.

    RegeneronCollaboration for cemdisiran

    Regeneron remains on track to submit a U.S. regulatory application for cemdisiran in generalized myasthenia gravis in Q1 2026.

    NovartisLeqvio royalties

    Driven by higher Leqvio sales.

    Risks & headwinds

    5
    Q1 2026 International TTR Revenue DeclineQ1 2026

    approximate $25 million reduction

    Mitigation: Management expects international markets to return to quarter-on-quarter growth for the balance of the year as increasing volume outweighs reduced price.

    Q1 2026 U.S. TTR Revenue Growth ModerationQ1 2026

    more modest quarter-over-quarter TTR growth

    Mitigation: Management expects higher quarterly growth for the balance of the year in the U.S. beyond Q1.

    AMVUTTRA Net Price ErosionFY26

    mid-single-digit net price decrease

    Mitigation: This dynamic is fully integrated into the 2026 outlook. Company is well-positioned from an access standpoint and has established credibility and durability of the franchise.

    Potential Competitive Entry in ATTR-CM2026

    competitor silencer data expected this year

    Mitigation: Management believes additional entrants will help drive diagnosis and treatment rates, expanding the category. Alnylam feels well-positioned with AMVUTTRA's rapid and deep knockdown profile, strong clinical data, and convenient quarterly dosing. Existing broad label provides data for both on and off stabilizer.

    Prior Safety Concerns with Huntington's Disease Therapies

    NfL increases, cerebral ventricular enlargement

    Mitigation: Alnylam's ALN-HTT02 program is specifically looking for safety and durable knockdown (>50%) in its Phase I study to avoid prior issues.

    What to watch in Q1 FY26

    5

    International TTR Revenue Growth

    beyond Q1 FY26
    Currentapproximate $25 million reduction in Q1 FY26
    Targetreturn to quarter-on-quarter growth

    Why it matters

    To confirm that increasing volume in international markets outweighs the impact of reduced pricing, supporting full-year TTR guidance.

    For the balance of the year, we expect our international markets will return to quarter-on-quarter growth as the impact of increasing volume outweighs reduced price.

    Q&A highlights

    5

    Seeking details on new patient uptake and the proportion of first-line use for AMVUTTRA versus switches from tafamidis, and how this is factored into 2026 guidance.

    Management expressed strong confidence in AMVUTTRA's launch fundamentals, citing improved first-line access, strengthening physician/patient preference, and continued category growth. They reiterated that these trends, observed heading into JPM, continue to build and support the 2026 guidance.

    “what really drives our confidence in reiterating the guidance is really is the fundamentals. If you think about it, we've actually improved our first-line access. We're clearly seeing a strengthening physician and patient preference and even more importantly, continued category growth with more patients entering the market.”

    asked by Paul Matteis · answered by Tolga Tanguler

    2 min read6 chapters

    Detailed Narrative

    01

    2025 Achievements & GAAP Profitability

    Alnylam achieved a landmark year in 2025, marked by the approval of AMVUTTRA for ATTR cardiomyopathy and nearly $3 billion in combined net product revenues, an 81% increase over 2024. The company successfully met or exceeded all its P5x25 goals, notably achieving GAAP profitability for the full year 2025, a milestone expected to be sustained going forward⏳. This financial performance was significantly driven by the strong launch of AMVUTTRA.

    02

    Alnylam 2030 Goals & Strategic Pillars

    The company introduced its new 5-year goals, Alnylam 2030, structured around three strategic pillars. These include achieving global TTR leadership with nucresiran launches in 2028 (polyneuropathy) and 2030 (cardiomyopathy), growing through sustainable innovation to deliver 2+ blockbuster potential medicines beyond TTR, and scaling with discipline to achieve over 25% revenue CAGR and approximately 30% non-GAAP operating margin by 2030. The R&D investment is projected at 30% of revenues to fuel internal and selective external innovation.

    03

    Commercial Performance & TTR Franchise Momentum

    Q4 FY25 saw strong commercial growth, with combined net product revenues reaching $995 million, up 121% year-over-year. The TTR franchise was the primary growth engine, generating $858 million, a 151% year-over-year increase. The rare disease portfolio (GIVLAARI and OXLUMO) also contributed $136 million in Q4, becoming a $0.5 billion franchise in 2025. AMVUTTRA's early launch momentum in ATTR-CM is strong, rapidly establishing itself as an important choice in new treatment starts and gaining traction in first-line patients, supported by broad payer access.

    04

    Pipeline Expansion & Innovation

    Alnylam significantly expanded its pipeline in 2025, initiating three Phase III studies: ZENITH for zilebesiran in hypertension, TRITON-CM for nucresiran in ATTR-CM, and TRITON-PN for nucresiran in hereditary ATTR polyneuropathy. Four new proprietary programs (ALN-2232 for ACVR1C, ALN-5288 for MAPT/tau, ALN-4285, ALN-4915) entered the clinic, alongside five partner-led programs. The company also launched siRELIS, an enzymatic ligation-based RNAi manufacturing platform designed to expand capacity and reduce costs.

    05

    Key Pipeline Assets & Upcoming Data

    Several programs represent the next wave of transformative RNAi therapeutics. Zilebesiran aims for continuous blood pressure control with twice-yearly dosing. Nucresiran is expected to be a best-in-class treatment for ATTR-CM. ALN-2232 (ACVR1C) targets durable weight loss, particularly visceral fat. ALN-5288 (MAPT/tau) and ALN-HTT02 (Huntington's disease) address neurological disorders. ALN-6400 targets bleeding disorders. Clinical derisking data for ALN-6400, Huntington's, and ACVR1C programs are expected in H2 2026.

    06

    External Innovation Strategy

    While primarily focused on its internal pipeline, Alnylam is open to selective external innovation that complements its existing portfolio and R&D pipeline. The company maintains a high scientific and financial bar for such opportunities, aiming to accelerate internal innovation and access new technologies or earlier-stage medicines. This strategy is supported by its strengthening financial position.

    AI-generated summary of the company’s earnings call. Not investment advice.