Executive Summary

Q3 delivered a clean beat: total revenues $1.25B (+149% YoY) on strong AMVUTTRA uptake and a $300M Roche milestone; non‑GAAP diluted EPS $2.90 versus Street $0.55*, while GAAP diluted EPS was $1.84 . Consensus: Revenue $974M*, Primary EPS $0.55*.
TTR franchise strength: AMVUTTRA/ONPATTRO net product revenue reached $724M (+135% YoY), with U.S. TTR net revenue of $543M and AMVUTTRA ATTR‑CM demand roughly doubling QoQ; total net product revenue rose to $851M (+103% YoY) .
Guidance raised again: FY25 total net product revenue to $2.95–$3.05B (from $2.65–$2.80B) and TTR to $2.475–$2.525B; non‑GAAP OpEx narrowed to $2.15–$2.20B .
Near‑term watch items: rising COGS/royalties (COGS at 23.2% of product revenue; CFO flagged lower Q4 gross margin) and a DOJ subpoena on government price reporting; ex‑U.S. ATTR‑CM launches largely a 2026 story .

Consensus estimates marked with * are retrieved from S&P Global.

What Went Well and What Went Wrong

What Went Well

AMVUTTRA ATTR‑CM launch momentum: patient demand “roughly doubled” vs Q2; broad first‑line uptake and most patients with $0 OOP; prescriber growth “robust” .
TTR franchise outperformance: TTR net product revenue $724M (+135% YoY); U.S. TTR revenue $543M, up 42% QoQ; global TTR revenue up 33% QoQ; Rare portfolio steady at $127M (+14% YoY) .
Non‑GAAP profitability surge: non‑GAAP operating income $476M (vs $(31)M in 3Q24), driven by top‑line strength and $300M Roche milestone recognition tied to ZENITH Phase 3 first patient dose .

What Went Wrong

COGS/royalty headwind: COGS rose to 23.2% of net product revenue (vs 19.5% in 3Q24); CFO guided Q4 gross margin down as in‑vitro royalty rates step up with higher AMVUTTRA sales .
ONPATTRO softness: down 22% YoY (switches to AMVUTTRA) and impacted by gross‑to‑net; management noted ONPATTRO declined from Q2 due to a one‑time Medicaid adjustment that did not repeat .
Legal overhang: DOJ subpoena seeks documents on government price reporting for AMVUTTRA, ONPATTRO, OXLUMO, and GIVLAARI; management intends to cooperate but offered no further detail .

Financial Results

Headline P&L vs Prior Periods and Consensus (Q3’24 → Q2’25 → Q3’25; Consensus Q3’25)

Metric	Q3 2024	Q2 2025	Q3 2025	Q3 2025 Consensus
Total Revenues ($)	$500.9M	$773.7M	$1,249.0M	$974.1M*
Net Product Revenues ($)	$420.1M	$672.2M	$851.1M	—
GAAP Net Income (Loss) ($)	$(111.6)M	$(66.3)M	$251.1M	—
GAAP Diluted EPS ($)	$(0.87)	$(0.51)	$1.84	—
Non‑GAAP Operating Income ($)	$(31.1)M	$95.5M	$476.2M	—
Non‑GAAP Diluted EPS ($)	$(0.50)	$0.32	$2.90	$0.55*
COGS as % of Net Product	19.5%	21.1%	23.2%	—

Notes: CFO indicated Q3 gross margin on product sales ~77% and expects lower gross margin in Q4 due to higher royalty rates . Consensus estimates marked with * are retrieved from S&P Global.

Segment/Product Revenue Breakdown (YoY)

Metric	Q3 2024	Q3 2025	YoY %
AMVUTTRA	$258.6M	$685.3M	165%
ONPATTRO	$50.3M	$39.1M	(22%)
Total TTR	$308.9M	$724.4M	135%
GIVLAARI	$71.0M	$73.9M	4%
OXLUMO	$40.2M	$52.8M	31%
Total Rare	$111.3M	$126.7M	14%
Net Product Revenues	$420.1M	$851.1M	103%
Roche Collaboration	$16.3M	$326.6M	>500%
Regeneron Collaboration	$37.9M	$22.5M	(41%)
Royalty Revenue	$23.4M	$46.2M	98%
Total Revenues	$500.9M	$1,249.0M	149%

KPIs and Operating Items

U.S. TTR net product revenue: $543M (Q3) .
Estimated Q3 AMVUTTRA ATTR‑CM revenue: ~$300M (mgmt estimate; assumes steady PN growth) .
AMVUTTRA ATTR‑CM patient demand: ~2x QoQ .
COGS as % of net product revenue: 23.2% (Q3) vs 19.5% (3Q24) .
Gross‑to‑net dynamics: mid‑single‑digit net price decline for TTR franchise in 2025; ONPATTRO gross‑to‑net impacted Q3 vs Q2 (Medicaid one‑time in Q2) .
Cash, cash equivalents and marketable securities: $2.7B at 9/30/25; refinancing activity included $661M 0.00% converts due 2028 and partial repurchase of 1.00% 2027 notes; new $500M revolver .
Stockholders’ equity: $233.9M at 9/30/25 .

Guidance Changes

Metric	Period	Previous Guidance (7/31/25)	Current Guidance (10/30/25)	Change
Total TTR Net Product Revenues	FY 2025	$2,175–$2,275M	$2,475–$2,525M	Raised
Total Rare Net Product Revenues	FY 2025	$475–$525M	Reiterated	Maintained
Total Net Product Revenues	FY 2025	$2,650–$2,800M	$2,950–$3,050M	Raised
/listened
Net Product Revenue Growth vs 2024 (FX @ 9/30)	FY 2025	61%–70%	79%–85%	Raised
Net Product Revenue Growth vs 2024 (CER)	FY 2025	59%–68%	78%–84%	Raised
Collaborations & Royalties	FY 2025	$650–$750M	Reiterated	Maintained
GAAP R&D and SG&A	FY 2025	$2,445–$2,575M	$2,495–$2,575M	Narrowed/Updated
Non‑GAAP R&D and SG&A	FY 2025	$2,100–$2,200M	$2,150–$2,200M	Narrowed
Non‑GAAP Operating Income	FY 2025	Achieve profitability	Reiterated	Maintained

Management added color that non‑GAAP operating expense guidance is narrowed to $2.15–$2.20B (upper end of prior range) .

Earnings Call Themes & Trends

Topic	Previous Mentions (Q‑2 and Q‑1)	Current Period (Q3 2025)	Trend
AMVUTTRA ATTR‑CM launch	Q1: U.S. approval and early launch underway; reiterated FY guide . Q2: First full quarter; TTR $544M; guidance raised; ~1,400 CM patients on drug by 6/30 .	Demand roughly doubled QoQ; broad first‑line use; $543M U.S. TTR; CM ~ $300M est .	Accelerating adoption; expanding prescriber base.
Ex‑U.S. rollout	Q1: Anticipated JP/EU approvals in mid‑2025 . Q2: Approvals in EU/UK/JP; ex‑U.S. contribution modest near term .	Ex‑U.S. revenue modest in Q4; broader launches largely 2026; early progress in Japan, Germany ongoing pricing .	International inflection expected 2026.
Access & payers	Q1/Q2: Building access, broad patient support .	No headwinds; payers allowing first‑line use; most patients $0 OOP; 2026 policies similar to 2025 .	Stable/favorable access.
Pricing/Gross‑to‑Net	Q2: COGS% + royalty rate rising with AMVUTTRA .	Mid‑single‑digit net price decline for TTR in 2025; Q3 GTN higher vs Q2; Q4 gross margin to decline .	Margin pressure from royalties.
Pipeline (zilebesiran CVOT ZENITH)	Q1: Plan to initiate CVOT H2’25 . Q2: KARDIA‑3 late‑breaker to inform CVOT .	ZENITH started; $300M Roche milestone recognized; KARDIA‑3 subgroup data supportive .	Executing into Phase 3 outcomes.
Pipeline (nucresiran TRITON)	Q2: TRITON‑CM initiated; TRITON‑PN planned .	TRITON‑PN initiation underway; CM underway; topline PN 2028 .	Advancing both CM and PN studies.
Legal/Regulatory	—	DOJ subpoena on government price reporting; company cooperating .	New risk factor.
Diagnostics/Macro	—	CMS proposed cut to PYP scan reimbursement queried; management not seeing system anxiety; monitoring .	Watch reimbursement policy.

Management Commentary

“Our commercial performance was driven by TTR franchise revenues of $724 million… with growth largely attributable to the AMVUTTRA ATTR‑CM launch in the U.S., where we achieved total TTR revenues of $543 million” – CEO Yvonne Greenstreet .
“Patient demand roughly doubled quarter over quarter… nearly all patients have access to AMVUTTRA as a first line treatment option… most patients pay zero out of pocket.” – CCO Tolga Tanguler .
“We are increasing our net product revenue guidance… to $2.95–$3.05 billion… The upper end of [Q4 TTR] range is very close to what we’ve delivered in both Q2 and Q3.” – CFO Jeff Poulton .

Q&A Highlights

First‑line vs switch dynamics: Growing first‑line share; maintaining leadership in second‑line among stabilizer progressors; broad adoption across academic/community prescribers .
Ex‑U.S. pricing/launch: Compelling pricing profile in Japan; Germany in early reimbursement talks; ex‑U.S. to contribute modestly near‑term with broader ramp in 2026; limited EU field expansion needed due to centers of excellence model .
Inventory and gross‑to‑net: Channel inventory up with ramping demand; Q3 gross‑to‑net increased (ONPATTRO impacted by prior one‑time Medicaid in Q2); expect mid‑single‑digit net price decline for TTR in 2025 .
CMS PYP imaging reimbursement: Monitoring proposed cuts; not seeing anxiety in health systems yet .
Legal: DOJ subpoena on price reporting; company will cooperate; no further commentary .

Estimates Context

Metric (Q3 2025)	Consensus	Actual	Surprise
Total Revenues ($)	$974.1M*	$1,249.0M	+28.2%
Primary (Non‑GAAP Diluted) EPS ($)	$0.55*	$2.90	Large beat

Drivers of upside: $300M milestone from Roche tied to ZENITH Phase 3 first‑patient dosing and robust AMVUTTRA ATTR‑CM uptake; royalty revenue also doubled YoY with higher Leqvio sales . Margin headwinds from rising royalty rates partially offset at the operating line by scale and collaboration revenue .

Consensus values marked with * are retrieved from S&P Global.

Key Takeaways for Investors

AMVUTTRA ATTR‑CM is scaling faster than expected; U.S. TTR +42% QoQ with demand doubling, supporting another guidance raise; expect Q4 TTR $850–$900M run‑rate per CFO framing .
Revenue quality mixed (clean product growth plus one‑time $300M milestone); nevertheless, net product trends alone imply continued upside momentum into Q4 .
Watch near‑term margin pressure: increasing in‑vitro royalty rates will weigh on gross margin in Q4; plan for lower GM% despite higher sales .
Ex‑U.S. launches are a 2026 catalyst wave (Japan early progress; EU pricing underway); little near‑term contribution expected in Q4 2025 .
Legal and policy risks: DOJ subpoena on price reporting introduces uncertainty; proposed CMS PYP imaging reimbursement cuts are being monitored but not impacting demand yet .
Pipeline continues to de‑risk growth beyond TTR: ZENITH CVOT initiated (Roche alliance), TRITON PN/CM moving; additional early programs (ALN‑6400, ALN‑5288) broaden optionality .
Near‑term setup: Positive estimate revisions likely as Street absorbs stronger TTR run‑rate and higher FY revenue guide; traders should watch Q4 gross‑to‑net and royalty drag vs top‑line acceleration for stock reaction catalysts .

ALNYLAM PHARMACEUTICALS, INC. (ALNY)·Q3 2025 Earnings Summary