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    ALNY
    Earnings call· Sep 2025(Q3 FY25)

    ALNYLAM PHARMACEUTICALS, INC. ALNY

    Oct 30, 2025 Source

    Executive summary

    Alnylam Q3 FY25 — AMVUTTRA CM Drives Strong Revenue Growth and Pipeline Expansion

    Alnylam reported a robust Q3 FY25, driven by exceptional commercial performance of its TTR franchise, particularly the AMVUTTRA ATTR-CM launch in the U.S. The company significantly raised its full-year net product revenue guidance, underscoring confidence in its commercial strategy. Alongside strong financial results, Alnylam advanced its pipeline with two new Phase III trials and several earlier-stage programs, aiming for sustainable innovation and long-term value creation.

    Highlights

    5

    • TTR franchise revenues reached $724 million, representing 135% year-over-year growth.

    • AMVUTTRA cardiomyopathy launch in the U.S. drove an approximate doubling of TTR cardiomyopathy revenue compared to the prior quarter, estimated at $300 million.

    • Total net product revenues were $851 million, up 103% year-over-year.

    • Full-year 2025 total net product revenue guidance was increased to a range of $2.95 billion to $3.05 billion, representing a $275 million or 10% increase at the midpoint.

    • Two new Phase III trials initiated: ZENITH (zilebesiran in hypertension) and TRITON-PN (nucresiran in hATTR-PN).

    Concerns

    4

    • An increase in U.S. gross-to-net deductions primarily impacted ONPATTRO, reducing U.S. reported quarter-over-quarter growth in the hATTR-PN business.

    • Gross margin on product sales decreased to 77% for the quarter, compared with 80% in Q3 2024, primarily due to increased AMVUTTRA royalties.

    • Gross margin on product sales is expected to decrease further in Q4 due to increasing AMVUTTRA royalty rates.

    • The company received a subpoena from the U.S. Attorney General regarding government price reporting.

    Guidance & targets

    6
    CategoryTargetConfidence
    Total Net Product Revenue
    $2.95 billion to $3.05 billion
    high materiality
    High
    Total TTR Guidance Range
    $2.475 billion to $2.525 billion
    high materiality
    High
    Total Rare Franchise Guidance Range
    $475 million to $525 million
    medium materiality
    High
    Non-GAAP Operating Expense Guidance
    $2.15 billion to $2.2 billion
    medium materiality
    High
    Zilebesiran Launch
    around 2030
    high materiality
    Medium
    TRITON-PN Top-line Results
    2028
    medium materiality
    High

    Segment performance

    2
    SegmentRevenueYoYQoQMargin
    TTR Franchise
    Primary growth engine, driven by U.S. patient demand and AMVUTTRA ATTR-CM label expansion. International AMVUTTRA ATTR-CM launches anticipated across 2026.
    U.S. TTR net sales: $543 millionU.S. TTR growth QoQ: 42%U.S. TTR growth YoY: 194%Ex-U.S. TTR growth QoQ: 13%Ex-U.S. TTR growth YoY: 46%AMVUTTRA ATTR-CM net product revenues (U.S.): ~$300 million (doubled from Q2)
    		$724 million135%33%—
    Rare Disease Portfolio
    Continued momentum driven by ongoing patient demand, despite short-term shifts from timing of orders in partner markets.
    		$127 million14%——

    Operational metrics

    15
    Total Net Product Revenues
    $851 million103% growth versus 2024
    Q3 FY25

    Combined net product revenues for the quarter.

    Collaboration Revenue
    $352 million$294 million increase versus last year
    Q3 FY25

    Primarily due to revenue recognized under collaboration and license agreement with Roche, including a $300 million milestone.

    Royalty Revenue
    $46 milliondoubling compared with last year
    Q3 FY25

    Driven by higher LEQVIO sales as Novartis grows the product globally.

    Gross margin on product sales
    77%compared with 80% in Q3 2024
    Q3 FY25

    Decrease in margin primarily driven by increased royalties on AMVUTTRA.

    Non-GAAP R&D expenses
    $310 millionincreased 23% compared to last year
    Q3 FY25

    Increase primarily driven by costs associated with Phase III clinical studies.

    Non-GAAP SG&A expenses
    $263 millionincreased 35% compared to last year
    Q3 FY25

    Increase primarily driven by investments for the AMVUTTRA ATTR cardiomyopathy launch in the U.S.

    Non-GAAP operating income
    $476 million$507 million increase compared with last year
    Q3 FY25

    Driven primarily by strong top-line results in product sales and collaboration revenue.

    Cash, cash equivalents and marketable securities
    $2.7 billionsimilar amount at the end of 2024
    end of Q3 FY25

    Cash balance at the end of the quarter.

    Convertible notes raised
    more than $600 million
    September

    Raised via the issuance of new convertible notes as part of refinancing.

    Convertible senior notes repurchased
    $1.1 billion
    Q3 FY25

    Used cash to repurchase a large portion of convertible senior notes due in 2027.

    Revolving credit facility
    $500 million
    Q3 FY25

    Entered into a new revolving credit facility for flexible liquidity.

    TTR franchise net price decline
    mid-single-digityear-over-year
    FY25

    Expected net price decline for the TTR franchise on a year-over-year basis.

    Health system setup for AMVUTTRA CM
    nearly all 170complete
    Q3 FY25

    Nearly all priority health systems are now using AMVUTTRA, driving broad utilization.

    AMVUTTRA treatment accessibility
    90%
    Q3 FY25

    Approximately 90% of U.S. patients can receive AMVUTTRA treatment within 10 miles of home.

    PYP scintigraphy reimbursement cut proposal
    57%from $1,300 to $500
    proposed

    CMS is proposing to cut reimbursement for PYP scintigraphy.

    Industry KPIs

    6
    MetricValueDetails
    Launch access metricsnearly all
    Pipeline read out calendarTRITON-PN top-line results expected 2028
    Product franchise net sales$724 millionUSD
    Therapeutic drug market sharegrowing
    Clinical trial efficacy safety data37% reduction%
    Collaboration milestone royalty revenue$300 millionUSD

    Deals & partnerships

    3
    RocheCollaboration and license agreement$300 million

    Revenue recognized under the collaboration and license agreement with Roche.

    Convertible note holdersRefinancing of convertible notesRaised more than $600 million

    Raised capital via the issuance of new convertible notes and repurchased existing notes.

    UndisclosedRevolving credit facility$500 million

    Entered into a $500 million revolving credit facility.

    Risks & headwinds

    4
    Increase in U.S. gross-to-net deductionsQ3 FY25

    Primarily impacted ONPATTRO, reducing U.S. reported Q-over-Q growth in hATTR-PN business.

    Decrease in gross margin on product salesQ3 FY25, Q4 FY25

    77% in Q3 FY25, compared with 80% in Q3 2024. Expected to decrease further in Q4.

    Mitigation: Driven by increased AMVUTTRA royalties due to higher sales.

    Subpoena from U.S. Attorney GeneralOngoing

    Not quantified

    Mitigation: Intend to work with the U.S. Attorney's office to produce requested documents and address potential concerns regarding government price reporting.

    Proposed cut in PYP scintigraphy reimbursement by CMSProposed

    57% cut (from $1,300 to $500)

    Mitigation: Management anticipates more diagnosis and scanning, needs to understand how reimbursement plays out; no anxiety or concerns seen in health systems.

    What to watch in Q4 FY25

    5

    AMVUTTRA ATTR-CM U.S. launch momentum

    Next quarter and into next year
    CurrentPatient demand roughly doubled QoQ in Q3
    TargetContinued strong patient adds and first-line share growth

    Why it matters

    Sustained growth of the lead franchise is key to revenue targets and market leadership.

    Look, we're only 2 quarters into this launch. And we've already raised guidance twice. I think that really speaks volume about the depth and the durability and our confidence in how we see these categories continue to grow.

    Q&A highlights

    6

    How is AMVUTTRA CM performing in first-line vs. switchers, any combo use, and what is the clarity on ex-U.S. pricing?

    AMVUTTRA CM shows broad and balanced adoption, with growing first-line share and leadership in second-line. Combo use is minimal but expected to increase with tafamidis generics. Ex-U.S. pricing is compelling in Japan, early in Germany, and broader European launches are a mid-to-late 2026 story.

    “Look, we're really pleased with another strong quarter. As we indicated, demand doubled in cardiomyopathy and utilization remains very broad and balanced.”

    asked by Salveen Richter · answered by Tolga Tanguler

    2 min read6 chapters

    Detailed Narrative

    01

    TTR Franchise Performance and AMVUTTRA CM Launch

    Alnylam's TTR franchise delivered $724 million in global net revenues, marking a 33% quarter-over-quarter and 135% year-over-year growth. The U.S. TTR franchise alone grew 42% QoQ and 194% YoY, primarily driven by the AMVUTTRA ATTR-CM label expansion. The CM indication is estimated to have contributed approximately $300 million in net product revenues this quarter, doubling from Q2, reflecting sustained launch momentum and broad patient demand.

    02

    AMVUTTRA ATTR-CM U.S. Launch Dynamics

    The U.S. launch of AMVUTTRA ATTR-CM shows broad and balanced adoption across newly diagnosed patients and those progressing on stabilizers, in both academic and community settings. Health system setup is effectively complete, with nearly all 170 priority health systems now utilizing AMVUTTRA. Payer coverage remains strong, providing broad first-line access with minimal out-of-pocket costs for most patients, reinforcing confidence in the product's market penetration.

    03

    Pipeline Advancement: Zilebesiran in Hypertension

    The ZENITH Phase III cardiovascular outcomes trial for zilebesiran in hypertension has initiated, enrolling approximately 11,000 patients to evaluate a 300mg dose every six months. This follows positive KARDIA-3 Phase II results demonstrating clinically meaningful reductions in office systolic blood pressure. The company anticipates a potential launch for zilebesiran around 2030, contingent on successful study outcomes and regulatory approval.

    04

    Pipeline Advancement: Nucresiran in hATTR-PN

    The TRITON-PN study for nucresiran in hereditary TTR polyneuropathy (hATTR-PN) is set to initiate shortly, complementing the previously started TRITON-CM trial. This open-label Phase III trial will enroll approximately 125 patients, randomizing them to nucresiran or vutrisiran. Top-line results from TRITON-PN are expected in 2028, further advancing Alnylam's next-generation silencer program.

    05

    Novel Programs: ALN-6400 for HHT and ALN-5288 for Alzheimer's

    Alnylam has moved ALN-6400, targeting plasminogen, into a Phase II trial for hereditary hemorrhagic telangiectasia (HHT), a significant inherited bleeding disorder. Initial Phase I data demonstrated proof of mechanism with an antifibrinolytic effect. Additionally, a Phase I trial for ALN-5288, targeting MAPT (tau) for Alzheimer's disease and other tauopathies, has been initiated, expanding the company's neurodegenerative disease pipeline.

    06

    Financial Performance and Outlook

    Total product revenues reached $851 million, a 103% increase year-over-year, contributing to a non-GAAP operating income of $476 million, up $507 million YoY. The company increased its full-year 2025 net product revenue guidance to $2.95 billion to $3.05 billion. Non-GAAP R&D expenses rose 23% due to Phase III study initiations, and non-GAAP SG&A increased 35% to support the AMVUTTRA CM launch.

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