Executive Summary

Vertex delivered $2.77B total revenue (+3% YoY), but missed Wall Street consensus on revenue and non-GAAP EPS; management raised the low end of FY25 revenue guidance by $100M to $11.85–$12.0B, signaling confidence in CF, CASGEVY and JOURNAVX ramps .
Revenue softness ex-U.S. was driven by an isolated Russia IP violation ($100M Q1 headwind; $200M for FY25), partially offset by strong U.S. demand and early ALYFTREK contribution; non-GAAP EPS of $4.06 reflected higher R&D and commercial investments .
Launch execution: >65 CASGEVY ATCs activated with ~90 first cell collections; >20,000 JOURNAVX prescriptions by April 18; 94M covered lives (42M unrestricted) and a major PBM deal (~22M lives) underpin coverage momentum .
Pipeline catalysts: three Phase 3 programs approaching interim or dosing completion in 2025 (pove in IgAN, inaxaplin in AMKD, zimislecel in T1D), setting up multiple potential filings in 2026; ALYFTREK approvals progress in EU and UK supports CF durability .

What Went Well and What Went Wrong

What Went Well

CF durability and diversification: continued strong TRIKAFTA/KAFTRIO performance and early ALYFTREK revenue ($53.9M), with U.S. revenue up 9% to $1.66B on demand and net realized pricing .
Launch traction: broad JOURNAVX coverage (94M lives, 42M unrestricted) and >20,000 prescriptions by April 18; a large PBM covering ~22M lives accelerates retail and discharge use cases .
Strategic progress and confidence: “Vertex delivered a strong start to 2025… grow and diversify the revenue base, progress multiple launches and advance the R&D pipeline” — CEO Reshma Kewalramani .

What Went Wrong

Ex-U.S. headwind: total ex-U.S. revenue fell 5% YoY due to Russia illegal copy product; management quantified ~$100M impact in Q1 and $200M for FY25, fully embedded in guidance .
GAAP profitability compression: a $379.0M intangible asset impairment (VX-264) reduced GAAP net income to $646M (vs $1.10B prior-year), highlighting non-GAAP reliance to reflect underlying performance .
Elevated OpEx: combined non-GAAP R&D, AIPR&D and SG&A rose 21% YoY to ~$1.23B, driven by Phase 3 programs and commercial build-out for pain, pressuring non-GAAP EPS to $4.06 vs $4.76 in Q1 2024 .

Financial Results

Revenues and EPS vs prior periods and consensus

Metric	Q1 2024	Q4 2024	Q1 2025 Actual	Q1 2025 Consensus*
Total Revenue ($USD Billions)	2.6906	2.9120	2.7702	2.8609*
Non-GAAP Diluted EPS ($)	4.76	3.98	4.06	4.29*
GAAP Diluted EPS ($)	4.21	3.50	2.49	N/A

Values marked with * retrieved from S&P Global.

Narrative: YoY revenue +3% to $2.77B (press release stated growth), U.S. +9% to $1.66B; ex-U.S. −5% due to Russia IP violation . Non-GAAP EPS was $4.06 (down vs $4.76 prior year) as higher R&D/commercial investments and lower interest income weighed; GAAP EPS $2.49 included the $379M impairment .

Margins trend

Margin	Q3 2024	Q4 2024	Q1 2025
EBITDA Margin %	42.7432*	38.9285*	38.9683*

Values marked with * retrieved from S&P Global.

Segment/Product revenue breakdown

Product	Q1 2024 ($USD Millions)	Q1 2025 ($USD Millions)
TRIKAFTA/KAFTRIO	2,483.6	2,535.5
ALYFTREK	—	53.9
Other product revenues	207.0	170.8
of which: CASGEVY	—	14.2
of which: JOURNAVX	—	Insignificant
Product revenues, net	2,690.6	2,760.2
Other revenues	—	10.0
Total revenues	2,690.6	2,770.2

KPIs

KPI	Q1 2025
Activated CASGEVY ATCs (global)	>65
CASGEVY first cell collections	~90
CASGEVY infusions in Q1	8
JOURNAVX prescriptions (as of Apr 18)	>20,000
Covered lives (JOURNAVX)	94M covered; 42M unrestricted
Major PBM coverage	~22M commercial lives
U.S. revenue	$1.66B
ex-U.S. revenue	$1.11B

Guidance Changes

Metric	Period	Previous Guidance	Current Guidance	Change
Total Revenue	FY 2025	$11.75–$12.0B	$11.85–$12.0B	Raised low end by $0.10B
Combined GAAP R&D, AIPR&D & SG&A	FY 2025	$5.55–$5.70B	Unchanged	Maintained
Combined Non-GAAP R&D, AIPR&D & SG&A	FY 2025	$4.9–$5.0B	Unchanged	Maintained
Non-GAAP Effective Tax Rate	FY 2025	20.5%–21.5%	Unchanged	Maintained

Management reiterated immaterial tariff cost impact based on current rates given low China exposure and diversified supply chain .

Earnings Call Themes & Trends

Topic	Q3 2024 (Previous Mentions)	Q4 2024 (Previous Mentions)	Q1 2025 (Current Period)	Trend
CF franchise and ALYFTREK	Preparing vanzacaftor triple; broad EU reimbursement; TRIKAFTA rare mutation progress	ALYFTREK U.S. approval; expanding labels; younger cohorts	Early ALYFTREK uptake, once-daily convenience, additional 31 mutations; EU/UK approvals/CHMP opinion	Strengthening; label expansion and switching underway
CASGEVY rollout	First patient infused; 45 ATCs; expanding access	>50 ATCs; new SCD reimbursement in England; collections rising	>65 ATCs; ~90 collections; new EU/Middle East reimbursement; U.S. Medicaid model adoption -	Accelerating across regions
Acute pain (JOURNAVX)	PDUFA set (Jan 30, 2025)	FDA approval Jan 30; retail stocking begins; policy tailwinds (NOPAIN Act)	>20k Rx; 94M covered lives; PBM deal; discharge setting usage; revenue back-half weighted -	Building coverage and adoption
Tariffs / supply chain	Not emphasized	Tariff outlook immaterial; low China exposure	Reiterated immaterial impact under current tariffs	Stable, low risk (subject to change)
R&D execution (pove, inaxaplin, zimislecel)	Phase 3 initiations (RAINIER, VX-880 pivotal) -	Continued Phase 3 progress; LSR study outcome; multiple near-term milestones -	IA cohorts enrollment on track (pove IgAN, inaxaplin AMKD); zimislecel dosing completion this quarter; potential filings in 2026 - -	Milestones approaching; 2026 filing setup

Management Commentary

“Vertex delivered a strong start to 2025… grow and diversify the revenue base, progress multiple launches and advance the R&D pipeline… Vertex is poised to continue to deliver value for years to come.” — Reshma Kewalramani, CEO .
“Given the strong start… we are raising the low end of our 2025 total revenue guidance… we expect growth to accelerate over the remainder of the year” — Charles Wagner, CFO .
“ALYFTREK demonstrated noninferiority… lower sweat chloride… 31 additional mutations… once-daily dosing… we expect the majority of patients… will switch to ALYFTREK over time” — Stuart Arbuckle, COO -.
“More than 20,000 prescriptions were successfully filled for JOURNAVX as of April 18… coverage will expand through 2025” — Duncan McKechnie, incoming CCO -.

Q&A Highlights

ALYFTREK adoption drivers: clinicians value noninferiority, lower sweat chloride, broader mutation coverage and once-daily dosing; sweat chloride not routinely used in practice, but the aggregate profile is compelling -.
Tariffs: impact immaterial under current regimes; CF drug product manufacturing largely U.S.-based; minimal China exposure; outlook subject to sector-specific changes .
JOURNAVX coverage and scripts: PBM deal within 94M covered lives; discharge-centric initial usage across surgery and non-surgery settings; volume ramps ahead of revenue due to assistance programs; retail stocking ~33,000 pharmacies - -.
CASGEVY uptake: acceleration as ATCs gain experience; reimbursement expanding in EU/Middle East; 8 infusions completed in Q1; pathway to multibillion franchise - .
VX-993 and pain pipeline: Phase 2 acute pain readout in 2H25; goal to explore broader dose range and potentially exceed JOURNAVX efficacy; NAV1.7 combo optionality .

Estimates Context

Vertex missed consensus on revenue and non-GAAP EPS for Q1 2025; EBITDA also below consensus.

Metric	Q1 2025 Consensus*	Q1 2025 Actual	Beat/Miss
Total Revenue ($USD Billions)	2.8609*	2.7702	Miss (~$0.09B)
Non-GAAP EPS ($)	4.29*	4.06	Miss (~$0.23)
EBITDA ($USD Billions)	1.3125*	1.0795*	Miss (~$0.23B)

Values marked with * retrieved from S&P Global.

Drivers: Ex-U.S. revenue decline from Russia illegal copy product (−$100M Q1), and higher OpEx supporting launches and pivotal programs weighed on EPS relative to expectations . FY25 consensus revenue of ~$11.99B aligns with raised guidance range midpoint, supporting acceleration in H2 as coverage and volumes convert to revenue .

Key Takeaways for Investors

Near-term setup: Despite Q1 headline misses, the guidance raise and explicit Russia impact containment suggest trajectory improvement from Q2 onward as ALYFTREK switching and JOURNAVX coverage convert to revenue .
CF durability plus patent runway: ALYFTREK once-daily, lower royalty burden, and broader mutation coverage provide a strategic CF bridge to 2039; expect gradual switching momentum .
CASGEVY adoption: Expanding ATCs and reimbursement across regions underpin a multi-year ramp; watch U.S. Medicaid model execution and EU/ME access for cadence -.
Pain franchise potential: JOURNAVX’s broad label, policy tailwinds (NOPAIN Act), and payer wins support building a multibillion franchise; VX-993 offers optionality to enhance efficacy or combination strategies (NAV1.7) - .
2026 filing cycle: With povetacicept (IgAN/pMN), inaxaplin (AMKD), and zimislecel (T1D) nearing interim or dosing completion, multiple potential filings in 2026 provide diversified value-creation catalysts - -.
OpEx investment watch: Elevated R&D and commercial spend is deliberate to support late-stage programs and pain commercialization; monitor non-GAAP margin stabilization as launches mature .
Risk monitor: Tariff regime changes and Russia IP situation are contained in guidance but remain external variables; management indicates immaterial cost impact under current tariffs .

Appendix: Additional Data

Consolidated statements (key lines): GAAP net income $646.3M; non-GAAP net income $1,054.1M; GAAP vs non-GAAP tax rates 11.5% vs 18.8%; cash & investments $11.4B as of Mar 31, 2025 .
Guidance table details (footnotes): GAAP vs non-GAAP expense guidance differs primarily by $650–$700M stock-based comp; includes ~$100M AIPR&D in both .

Sources: Vertex Q1 2025 8-K/press release and financials -; Q1 2025 earnings call transcript - -; Q4 2024 8-K -; Q3 2024 press release -; UK MHRA ALYFTREK approval -; CHMP positive opinion -. Values marked with * retrieved from S&P Global.

VERTEX PHARMACEUTICALS INC / MA (VRTX)·Q1 2025 Earnings Summary