Executive Summary

Q4 2024 delivered strong top-line growth: total revenues of $593.2M (+35% YoY) and net product revenues of $450.8M (+30% YoY), driven by AMVUTTRA and continued Rare franchise strength . Non-GAAP EPS was $0.06 vs. GAAP EPS of -$0.65, aided by a $110.2M tax benefit .
TTR franchise revenue reached $342.6M in Q4 (+35% YoY), with AMVUTTRA at $286.5M and ONPATTRO at $56.1M; Rare franchise delivered $108.2M, led by GIVLAARI ($64.6M) and OXLUMO ($43.6M) .
2025 guidance reiterates combined net product revenues of $2.05–$2.25B, TTR $1.60–$1.725B, Rare $450–$525M, collaboration/royalty revenue $650–$750M, and non-GAAP profitability, contingent on AMVUTTRA ATTR-CM approval by Mar 23, 2025 (PDUFA) and launches in Germany/Japan in 2H25 .
Stock-relevant catalysts near term: AMVUTTRA (vutrisiran) ATTR-CM sNDA PDUFA Mar 23, 2025; Sanofi’s fitusiran PDUFA Mar 28, 2025 (royalties 15–30% tiered); R&D Day Feb 25, 2025; planned Phase 3 start for nucresiran in 1H25 .

What Went Well and What Went Wrong

What Went Well
- “2024 was another year of impressive execution… product revenues of over $1.6 billion, reflecting growth of 33% compared to 2023” (CEO) . Full-year non-GAAP operating income of $95.2M marks a profitability milestone .
- TTR franchise strength: Q4 TTR $343M (+35% YoY) with AMVUTTRA momentum despite new competition; U.S. hATTR-PN combined sales up 10% q/q and 42% YoY, driven by demand and patient switches from ONPATTRO (CCO) .
- Pipeline progress: sNDA acceptance for vutrisiran ATTR-CM (PDUFA Mar 23, 2025); nucresiran received FDA Orphan Drug Designation with Phase 3 planned 1H25; KARDIA-3 completed enrollment; multiple Phase 1 starts (CNS/metabolic) .
What Went Wrong
- Operating expense growth and royalty burden: higher GAAP and non-GAAP R&D/SG&A in Q4 and FY due to pipeline and launch prep; COGS % rose in Q4 (22.8%) on higher AMVUTTRA royalty rates .
- Margin pressure expected in 2025: CFO flagged lower product gross margins as AMVUTTRA grows and royalty tiers increase (average AMVUTTRA royalty ~21% in 2024, likely mid/high-20s as sales scale) .
- Collaboration revenue volatility: FY collaboration revenues fell vs. 2023 due to prior-year Roche upfront, offset partly by Regeneron modification and Novartis milestone; underscores variability of non-product revenue .

Financial Results

Metric	Q2 2024	Q3 2024	Q4 2024
Total Revenues ($M)	$659.8	$500.9	$593.2
Net Product Revenues ($M)	$410.1	$420.1	$450.8
Net Revenues from Collaborations ($M)	$227.3	$57.4	$106.9
Royalty Revenue ($M)	$22.4	$23.4	$35.4
GAAP Net Income (Loss) ($M)	$(16.9)	$(111.6)	$(83.8)
GAAP EPS (Basic)	$(0.13)	$(0.87)	$(0.65)
Non-GAAP Net Income (Loss) ($M)	$73.8	$(64.2)	$8.0
Non-GAAP EPS (Basic)	$0.58	$(0.50)	$0.06
COGS as % of Net Product Revenues	16.4%	19.5%	22.8%

Segment breakdown – Net Product Revenues

Segment ($M)	Q2 2024	Q3 2024	Q4 2024
ONPATTRO	$77.2	$50.3	$56.1
AMVUTTRA	$230.1	$258.6	$286.5
Total TTR	$307.4	$308.9	$342.6
GIVLAARI	$62.1	$71.0	$64.6
OXLUMO	$40.6	$40.2	$43.6
Total Rare	$102.7	$111.3	$108.2
Total Net Product Revenues	$410.1	$420.1	$450.8

KPIs and balance sheet highlights

KPI	Q2 2024	Q3 2024	Q4 2024
Cash, Cash Equivalents & Marketable Securities ($B)	$2.62	$2.78	$2.69
Non-GAAP Operating Income ($M)	$137.9	$(31.1)	$(13.5)
Tax Benefit / (Provision) ($M)	$(5.7)	$(2.9)	$110.2

Guidance Changes

Metric	Period	Previous Guidance	Current Guidance	Change
Total Net Product Revenues	FY2025	$2,050–$2,250M	$2,050–$2,250M	Maintained
Total TTR Net Product Revenues	FY2025	$1,600–$1,725M	$1,600–$1,725M	Maintained
Total Rare Net Product Revenues	FY2025	$450–$525M	$450–$525M	Maintained
Net Revenues from Collaborations & Royalties	FY2025	—	$650–$750M (incl. $300M Roche milestone assumption; fitusiran approval)	Newly provided
Non-GAAP R&D and SG&A	FY2025	—	$2,100–$2,200M (excl. $270–$330M SBC)	Newly provided
Non-GAAP Operating Income	FY2025	Achieve profitability	Achieve profitability	Maintained

Footnotes: Guidance assumes AMVUTTRA ATTR-CM U.S. approval by Mar 23, 2025 and Germany/Japan launches in 2H25; FX assumptions noted; collaboration revenue includes Roche Phase 3 initiation milestone for zilebesiran; royalty revenue assumes fitusiran approval by Mar 28, 2025 .

Earnings Call Themes & Trends

Topic	Previous Mentions (Q2 & Q3 2024)	Current Period (Q4 2024)	Trend
ATTR-CM launch readiness and payer/formulary timeline	Q2: preparation and scale-up; quarterly dosing, Part B access advantages ; Q3: continued prep, U.S. demand resilience despite competition	“Meaningful uptake in H2” as health system formulary additions take months; expanding VBAs; >1,000 alternative sites; >90% patients within 10 miles target (CCO)	Increasing operational detail; focus shifts to formulary timelines
Gross margin trajectory and royalty burden	Q2: expect lower margin as AMVUTTRA grows ; Q3: lower margins in Q4	2024 product GM ~81%; 2025 expected lower; AMVUTTRA royalties avg ~21% in 2024, trending mid/high-20s as tiers rise (CFO)	Heightened margin headwind clarity
Regulatory milestones	Q2: sNDA plan; ESC data ; Q3: filings U.S./EU	sNDA accepted; PDUFA Mar 23, 2025; nucresiran Phase 3 planned 1H25; fitusiran PDUFA Mar 28, 2025	Advancing to decision points
Value-based agreements (VBAs)	Q2: emphasize access principles	Plan to expand VBAs to ATTR-CM; commitment to outcomes-based access (CCO)	Growing emphasis
Tax dynamics	Not highlighted	Swiss valuation allowance release drove tax benefit; not fully recurring (CFO)	New detail
R&D execution breadth	Q2: KARDIA-3 underway; APP Phase II plans; multiple INDs by end-2025	KARDIA-3 completed enrollment; multiple new Phase 1s (HTT, 6400, 4324); CNS progress (mivelsiran)	Continued expansion

Management Commentary

CEO: “We look forward to potential global launches of vutrisiran in ATTR-CM this year… an inflection point for our TTR franchise” .
CFO: “For the first time, we delivered full year non-GAAP operating profit of $95 million… a significant milestone… enabling further investment in our R&D pipeline” .
CCO: “We are building for durable long-term success… optimizing access pathways at 170 health systems… expect uptake to be meaningful in the second half” .

Q&A Highlights

Payer policies and formulary timing: Expect policy establishment and formulary inclusion to take months post-approval, implying H2 ramp in demand .
Pricing and access mechanics: Existing J-code supports continuity; aim for smooth coverage with many patients at $0 co-pay; VBAs to be extended .
Label expectations: Team expects mortality and hospitalization benefits, plus functional capacity and quality of life benefits, reflected consistent with prespecified endpoints (CMO) .
Margins outlook: Product gross margins to compress with AMVUTTRA royalties rising; collaboration and royalty revenues can uplift total revenue margin; nucresiran lacks Sanofi royalty burden (future offset) .
Tax benefit: Release of Swiss valuation allowance drove Q4 tax benefit; future releases uncertain (CFO) .

Estimates Context

Wall Street consensus (S&P Global) for Q4 2024 EPS and revenue was requested but not available due to data access limits at time of analysis; as a result, we cannot label the quarter as a beat/miss versus consensus. If needed, we can refresh and compare once S&P Global data becomes available.

Key Takeaways for Investors

AMVUTTRA ATTR-CM PDUFA (Mar 23, 2025) is the dominant near-term catalyst; management’s 2025 guide embeds approval and early international launches—track formulary adoption and VBAs as determinants of the H2 ramp .
TTR franchise strength continues despite competition; AMVUTTRA growth is offset by ONPATTRO declines as patients switch, but net TTR expansion remains robust (+35% YoY in Q4) .
Expect margin pressure in 2025 from rising AMVUTTRA royalties; watch mix, collaboration milestones (Roche $300M), and royalty streams (fitusiran approval) to buffer total margin .
Execution on pipeline is broad-based: nucresiran Phase 3 initiation in 1H25 could be strategically important (no Sanofi royalties), while hypertension (zilebesiran) and CNS programs (mivelsiran, HTT) diversify growth optionality .
Non-GAAP profitability achieved in 2024; guidance targets sustaining profitability in 2025—monitor non-GAAP OpEx vs. launch and Phase 3 initiation pacing .
Trading setup: Pre-approval quiet period (from Mar 1) and PDUFA outcomes could drive volatility; an approval with strong label language (mortality/hospitalization) and efficient formulary traction likely supports guidance confidence .
Risk watch: Royalty tiering, timing of Roche milestone, payer/formulary lags, and competition in TTR markets could influence revenue trajectory and margins .

ALNYLAM PHARMACEUTICALS, INC. (ALNY)·Q4 2024 Earnings Summary