Executive Summary

Q2 2025 delivered a decisive beat: Total revenues of $0.774B and total net product revenues of $0.672B, +17% and +64% YoY, respectively; revenue beat S&P Global consensus by ~$0.111B, and Primary EPS (S&P definition) was $0.32 vs -$0.70 consensus, a major upside surprise . S&P Global values marked with *; Values retrieved from S&P Global.
TTR franchise inflected with AMVUTTRA’s ATTR-CM launch: TTR product revenue $0.544B (+77% YoY), ~1,400 ATTR-CM patients on therapy by quarter-end; U.S. access was broad and mostly first-line with minimal step-edit incidence, underpinning raised FY guidance .
FY 2025 guidance increased materially: Total net product revenues raised to $2.650–$2.800B (midpoint +27%); TTR franchise raised to $2.175–$2.275B (midpoint +34% vs prior guide) .
Margin headwinds reflect higher AMVUTTRA royalties; CFO expects product gross margin to trend lower in 2H25 as royalty rates step up, partly offset by strong volume and durable demand signals .
Pipeline/strategic catalysts: Fast Track for nucresiran in ATTR-CM, international approvals for AMVUTTRA in ATTR-CM, and decision to initiate a global Phase III CV outcomes trial for zilebesiran with Roche by year-end .

What Went Well and What Went Wrong

What Went Well

TTR launch momentum: $0.544B TTR net product revenue (+77% YoY), including AMVUTTRA $0.492B; ~1,400 ATTR-CM patients on therapy by June 30 with faster-than-anticipated payer and provider access . “Access ramped faster than expected… coverage is now confirmed… majority of patients have first-line access” — Tolga Tanguler .
Guidance raised on strength of CM: Total net product revenue guidance lifted to $2.650–$2.800B; TTR to $2.175–$2.275B; management emphasized confidence in sustainable growth trajectory and international contributions in 2H25 .
Regulatory/clinical progress: AMVUTTRA approved for ATTR-CM in EU, UK, Brazil, Japan; nucresiran TRITON‑CM Phase 3 initiated; FDA Fast Track for nucresiran; HELIOS‑B 42‑month data reinforced ACM and CV mortality reductions, supporting first‑line positioning .

What Went Wrong

Collaboration revenues fell sharply (-73% YoY) due to a $185M Regeneron one-time recognition in Q2’24; non-GAAP operating income declined to $95M vs $138M prior year .
Margins compressed: Product gross margin 79% vs 84% prior year; CFO guided to further GM pressure in 2H25 given higher AMVUTTRA royalties .
GAAP loss widened: Net loss of -$66.3M (EPS -$0.51) vs -$16.9M (EPS -$0.13) in Q2’24; higher SG&A from AMVUTTRA launch and increased R&D from Phase 3 startups contributed to higher operating costs .

Financial Results

Metric	Q2 2024	Q1 2025	Q2 2025
Total Revenues ($USD Billions)	$0.660	$0.594	$0.774
Net Product Revenues ($USD Billions)	$0.410	$0.469	$0.672
Net Revenues from Collaborations ($USD Billions)	$0.227	$0.099	$0.061
Royalty Revenue ($USD Billions)	$0.022	$0.026	$0.040
GAAP Net Income ($USD Billions)	-$0.017	-$0.057	-$0.066
GAAP Diluted EPS ($)	-$0.13	-$0.44	-$0.51
Non-GAAP Operating Income ($USD Millions)	$137.9	$74.8	$95.5
Total Operating Expenses ($USD Billions)	$0.611	$0.576	$0.790
Gross Profit Margin %	89.59%*	88.04%*	81.52%*
EBITDA ($USD Millions)	$63.6*	$32.5*	-$2.3*
EBITDA Margin %	9.64%*	5.47%*	-0.29%*
Values marked with * retrieved from S&P Global.

Segment/Product Revenue Breakdown

Metric	Q2 2024	Q2 2025
AMVUTTRA Net Product Revenues ($USD Millions)	$230.1	$492.0
ONPATTRO Net Product Revenues ($USD Millions)	$77.2	$52.5
Total TTR Net Product Revenues ($USD Millions)	$307.4	$544.5
GIVLAARI Net Product Revenues ($USD Millions)	$62.1	$80.8
OXLUMO Net Product Revenues ($USD Millions)	$40.6	$46.9
Total Rare Net Product Revenues ($USD Millions)	$102.7	$127.7
Total Net Product Revenues ($USD Millions)	$410.1	$672.2

KPIs

KPI	Q2 2025	Context
ATTR-CM Patients on AMVUTTRA (approx.)	~1,400	First full quarter post-approval
U.S. TTR Franchise QoQ Growth	~$170M increase	Driven primarily by CM demand
Estimated U.S. CM Revenue Contribution	~$150M	Based on demand in Q2
Distributor Days on Hand	~20 days (steady QoQ)	~$25M inventory benefit QoQ
Prescriber Base Growth	~3x QoQ	Broad adoption across cardio & multidisciplinary
First-line Access Across Payers	Majority first-line, minimal step edits (single digits)	Medicare FFS/MA and commercial

Guidance Changes

Metric	Period	Previous Guidance	Current Guidance	Change
Total TTR Net Product Revenues (AMVUTTRA, ONPATTRO)	FY 2025	$1,600M–$1,725M	$2,175M–$2,275M	Raised
Total Rare Net Product Revenues (GIVLAARI, OXLUMO)	FY 2025	$450M–$525M	$475M–$525M	Raised (low end)
Total Net Product Revenues	FY 2025	$2,050M–$2,250M	$2,650M–$2,800M	Raised
Net Product Rev Growth vs 2024 (current FX)	FY 2025	25%–37%	61%–70%	Raised
Net Product Rev Growth vs 2024 (CER)	FY 2025	26%–39%	59%–68%	Raised
Net Revenues from Collaborations & Royalties	FY 2025	$650M–$750M	Reiterated	Maintained
GAAP R&D and SG&A	FY 2025	$2,370M–$2,530M	$2,445M–$2,575M	Raised (reflects higher SBC)
Non-GAAP R&D and SG&A	FY 2025	$2,100M–$2,200M	Reiterated	Maintained
Non-GAAP Operating Income	FY 2025	Achieve profitability	Reiterated	Maintained

Earnings Call Themes & Trends

Topic	Previous Mentions (Q4 2024 and Q1 2025)	Current Period (Q2 2025)	Trend
U.S. AMVUTTRA ATTR-CM launch/access	sNDA accepted (Q4); launch underway with strong early indicators (Q1)	Majority first-line coverage across payers; minimal step edits; broad provider setup	Accelerating access/coverage
Pricing/Gross-to-Net	Not detailed (Q4); launch expectations (Q1)	Net price expected down mid-single-digits YoY; Part D rebate headwind; modestly higher 340B	Manageable GTN headwinds
Inventory/channel	Not highlighted (Q4/Q1)	~$25M inventory benefit QoQ; ~20 days on hand steady	Demand-driven stocking
First-line vs progressors	Early CM growth anticipated (Q1)	Balanced utilization across first-line and stabilizer-progressors; prescriber base tripled	Broadening mix
International launches	Approvals anticipated (Q1)	Approved/launching in EU, UK, Japan, Brazil	2H25 contribution expected
TTR pipeline	Plan for nucresiran Phase 3 (Q4/Q1)	TRITON‑CM initiated; Fast Track for nucresiran	Advancing
Hypertension pipeline (zilebesiran)	KARDIA-3 data pending; CVOT planning (Q1)	Phase III CVOT decision announced; ZENITH planned near year-end	Moving to outcomes

Management Commentary

“We are raising our total net product revenue guidance range by 27% at the midpoint, driven by an upward revision to our TTR franchise revenue guidance.” — Yvonne Greenstreet, CEO .
“Coverage is now confirmed… the large majority of patients have access to AMVUTTRA as a first-line treatment… Most patients are paying zero out-of-pocket.” — Tolga Tanguler, CCO .
“Gross margin on product sales was 79%… decrease driven by increased royalties on AMVUTTRA… expected to decrease as royalty rates increase.” — Jeff Poulton, CFO .
“FDA has granted Fast Track Designation to nucresiran for ATTR-CM; TRITON-CM Phase 3 is underway.” — Management .

Q&A Highlights

Pricing and GTN: Net price reduction for AMVUTTRA expected mid-single‑digits YoY; Part D rebate headwind; modestly higher 340B utilization .
Demand and inventory: ~$150M CM revenue contribution in Q2; ~20 days on hand steady; ~$25M inventory benefit QoQ, offset by GTN headwinds .
First-line vs progressors: Early stabilizer‑progressor uptake shifted to balanced mix with robust first-line new starts; prescriber base tripled QoQ .
Payer dynamics: First-line coverage across most plans; step edits present in single digits, manageable with patient support systems .
Combination use: Small portion of patients on combination therapy; may rise as tafamidis goes generic; currently limited .

Estimates Context

Metric	Consensus (S&P Global)	Actual	Beat/Miss
Revenue (Q2 2025)	$662.5M*	$773.7M	Bold beat: +$111.2M
Primary EPS (Q2 2025)	-$0.70*	$0.32*	Bold beat: +$1.02
FY 2025 Revenue	$3,729.2M*	Company guidance $2,650–$2,800B (net product); collab+royalty reiterated	Guidance implies higher product sales trajectory; consensus includes total revenue mix
Values marked with * retrieved from S&P Global.

Implications: Expect upward revisions to revenue and EPS models driven by faster U.S. CM uptake, international launches, and higher FY product guidance; margin assumptions should reflect rising AMVUTTRA royalties and GTN dynamics .

Key Takeaways for Investors

AMVUTTRA’s ATTR‑CM launch is the core driver: U.S. demand is strong, access broadly first‑line, and the franchise added ~$150M CM revenue in Q2; guidance magnitude suggests >$600M CM contribution in 2H if momentum persists .
FY guidance reset is material and credible: TTR midpoints +~~$550M and total product +~~$575M, with international CM launches beginning in 3Q; monitors should track payer policy stability and first‑line prescriber adoption .
Margin modeling needs updating: Product GM guided lower on higher royalties; incorporate net price moderation and Medicare Part D rebates into GTN and margin scenarios .
Collaboration revenue volatility continues: YoY decline reflects non‑recurring 2024 items; focus on recurring product revenue and royalty streams (e.g., fitusiran/Leqvio) .
Pipeline value accretion: Fast Track for nucresiran and ZENITH CVOT initiation for zilebesiran are medium‑term catalysts that can broaden Alnylam’s cardiometabolic footprint .
Risk checks: Watch potential changes in payer step edits (currently minimal), GTN headwinds, and inventory normalization; validate sustainability of first‑line patient starts trajectory .
Trading setup: The combination of a large revenue/EPS beat, a significant FY guidance raise, and tangible pipeline milestones supports positive estimate revisions and a constructive near‑term narrative.

ALNYLAM PHARMACEUTICALS, INC. (ALNY)·Q2 2025 Earnings Summary