Vertex's Q3 2025 Earnings Call: Key Contradictions in JOURNAVX Payer Coverage, ALYFTREK Transitions, and VX-828 Timelines

Date of Call: November 3, 2025

Financials Results

• Revenue: $3.08B, up 11% YOY
• EPS: $4.80 per share (non-GAAP), up 10% YOY

Guidance:

• 2025 total revenue expected to be $11.9B to $12.0B (~8%–9% growth at current FX).
• Full-year combined non-GAAP R&D + acquired IPR&D + SG&A expected ~$5.0B to $5.1B.
• Projected IPR&D charges remain ~ $100M for the year.
• Non-GAAP effective tax rate revised to 17%–18%.
• Guidance assumes >$100M CASGEVY revenue in 2025 and additional JOURNAVX contribution in Q4.

Business Commentary:

* Revenue Growth and Product Launch Success: - Vertex Pharmaceuticals reported revenue of $3.08 billion for Q3 2025, reflecting a double-digit growth compared to Q3 2024. - This growth was driven by the ongoing launches of new products such as ALYFTREK and JOURNAVX, and the global expansion of CASGEVY.

• CF Franchise Performance:
• The CF franchise contributed to strong double-digit growth, with enhanced survival benefits of therapies and expansion into new geographies like Brazil and Turkey.

• The launch and transition from TRIKAFTA to ALYFTREK, offering improved CFTR function and once-daily dosing, contributed significantly to this growth.

• Pain Franchise Expansion:

• The launch of JOURNAVX in moderate to severe acute pain has led to significant prescription volumes, with over 300,000 prescriptions filled by mid-October.

• The success is attributed to achieving broad payer coverage, hospital access, and positive clinical outcomes with substantial opioid reduction.

• Pipeline and Regulatory Milestones:

• In the renal medicine portfolio, Vertex achieved full enrollment in the RAINIER Phase 3 trial for pove in IgAN, with rapid enrollment and a potential submission for accelerated approval by the end of 2025.
• This progress is due to a compelling clinical profile and regulatory breakthrough designation for pove, aiming to address significant unmet needs in renal diseases.

Sentiment Analysis:

Overall Tone: Positive

• Management: “Vertex delivered strong performance across the board in Q3 with $3.08 billion in revenue, reflecting double-digit growth versus Q3 2024.” Management: “we have a clear line of sight to over $100 million in CASGEVY revenue this year.” Management: “we have completed full enrollment in the RAINIER Phase 3 trial… we will begin our submission for potential accelerated approval before the end of this year.”

Q&A:

• Question from Geoffrey Meacham (Citigroup Inc., Research Division): Status/update on ALYFTREK uptake, monitoring requirements, and how you view pove differentiation vs other BAFF/APRIL assets?
  Response: ALYFTREK: vast majority of newly eligible U.S. patients have started, transitions steady, ~ $0.5B sales in ~10 months; Pove: dual BAFF/APRIL inhibition, engineered for higher tissue distribution and potency plus monthly low-volume auto-injector drive differentiation and promising clinical signals on proteinuria/hematuria/Gd‑IgA1.

• Question from Salveen Richter (Goldman Sachs Group, Inc., Research Division): How should we read through proteinuria/Gd‑IgA1 changes to eGFR benefit for pove and update on PBM progress for the pain franchise?
  Response: Pove: reductions in proteinuria strongly correlate with eGFR stabilization and are expected to translate to long‑term benefit; Pain: in productive talks with the third PBM, access is expanding and the patient support program covers uncovered patients while prescriptions accelerate.

• Question from Jessica Fye (JPMorgan Chase & Co, Research Division): Current capital allocation priorities and preferred BD stage?
  Response: Top priority is reinvesting in internal/external innovation and commercialization; secondary priority is share buybacks; BD is opportunistic across stages—focus is strategic fit within Vertex's sandbox, not a fixed preferred phase.

• Question from Evan Seigerman (BMO Capital Markets Equity Research): Commercial importance of monthly low‑volume auto‑injector and Q4 dosing competitive advantage for pove?
  Response: Administration profile (monthly, low volume, at‑home auto‑injector) is a material differentiator—reduces patient burden, improves adherence and satisfaction—complementing mechanism and clinical profile to support best‑in‑class potential.

• Question from Tazeen Ahmad (BofA Securities, Research Division): What did the FDA see to grant breakthrough designation and rolling review for pove?
  Response: After a pre‑BLA meeting where the agency reviewed available data and filing plans, FDA granted Breakthrough and rolling review based on unmet need and the strength of the data/clinical program, enabling earlier submissions.

• Question from Terence Flynn (Morgan Stanley): Any update on the NOPAIN Act inclusion and will Phase IV data show time‑to‑discharge?
  Response: NOPAIN final list delayed by the government shutdown and advocacy continues; Phase IV enrollment complete in two studies, upcoming aesthetic/reconstructive data show substantial opioid reduction; discharge endpoints are in other studies and not ready yet.

• Question from Edward (Leerink Partners, on behalf of David Risinger): Of the 170M lives for JOURNAVX how many are unrestricted and what's PBM coverage; timing/details for VX‑828 data?
  Response: JOURNAVX: 113M of the 170M lives are unrestricted (no prior auth/no step edits), active conversations with the third PBM and Medicare plans; VX‑828: in patient cohort now, expect data next year.

• Question from Philip Nadeau (TD Cowen, Research Division): Current gross‑to‑net for JOURNAVX and outlook for 2026; timing/peak share transition from TRIKAFTA to ALYFTREK?
  Response: Gross‑to‑net currently elevated due to patient support program and remaining contracting; 2026 guidance not provided yet; ALYFTREK: management expects the majority of global TRIKAFTA patients to transition to ALYFTREK over the next couple of years.

• Question from Julian (Stifel, on behalf of Paul Matteis): Any updates on suzetrigine in chronic pain or plans to expand in pain via BD?
  Response: No new updates on suzetrigine; focus is on completing DPN Phase III programs (second DPN study starting) and exploring NaV1.7/1.8 strategies and combinations to expand into broader peripheral neuropathic pain.

• Question from Huidong Wang (Barclays Bank PLC, Research Division): Could pove actually improve eGFR over longer treatment versus competitors?
  Response: Management expects that substantial reductions in proteinuria seen with pove will translate to eGFR stabilization (and will present eGFR data from the IgAN program at ASN); long‑term improvements depend on sustained biomarker and clinical effects.

• Question from Mohit Bansal (Wells Fargo Securities, LLC, Research Division): Will Vertex pursue larger ($5–$10B) BD deals given scale and cash position?
  Response: BD strategy is guided by strategic fit within the sandbox and R&D priorities; Vertex is open to deals of any size if they align with its disease focus and translational/clinical rationale—deal size is secondary to fit.

• Question from Jake (William Blair, on behalf of Myles Minter): DM1 program timeline/update and CASGEVY adverse event reporting policy for commercial/clinical patients?
  Response: DM1: SAD completed, MAD ongoing in patients with results expected next year (safety and efficacy); CASGEVY AEs in trials are reported through clinical trial systems, while commercial AEs are reported via standard physician/company/FDA channels.

• Question from William Pickering (Sanford C. Bernstein & Co., LLC., Research Division): Competitive landscape in pMN versus IgAN and how you define the pMN addressable market?
  Response: pMN and IgAN are both B‑cell mediated but pMN is a smaller Western market (~150k) with less competitive intensity; Vertex believes pove has best‑in‑class potential in pMN and is leading the APRIL/BAFF class in pivotal development.

Contradiction Point 1

JOURNAVX Payer Coverage and Patient Support Program

It involves differing statements about the progress and plans for JOURNAVX's payer coverage and the use of patient support programs, which could impact financial projections and market access.

How many of the 170 million JOURNAVX users have unrestricted access, and what is the timeline for VX-828 data release? - Edward (for David Risinger, Leerink Partners)

2025Q3: As of June 30, we had executed agreements with 3 major PBMs covering 170 million pharmacy lives, 113 million of which are unrestricted, and now, we expect to have 100 million lives covered by January of next year. - Reshma Kewalramani(CEO)

How will the initial use of patient support programs affect gross to net, and what are expectations for future use in gross to net calculations? - Eliana Rachel Merle (UBS)

2025Q2: We are currently using patient support programs to provide seamless patient experiences, but as national coverage increases, that program will be retired by the end of the year. - Reshma Kewalramani(CEO)

Contradiction Point 2

ALYFTREK Patient Transitions and Market Analysis

It involves differing perspectives on the pace and expectations for patient transitions from TRIKAFTA to ALYFTREK, which impacts revenue projections and market positioning.

Can you provide an update on ALYFTREK's patient switching and monitoring requirements? - Geoffrey Meacham(Citigroup)

2025Q3: The pace of patient transitions remains satisfactory. - Duncan J. McKechnie(CMO)

Any updates to JOURNAVX's Phase III design following regulatory feedback? Any early data on ALYFTREK? - Geoffrey Meacham(Citigroup)

2024Q4: We expect that over time, a majority of those -- so maybe the majority of those patients will transition on to ALYFTREK. - Stuart Arbuckle(COO)

Contradiction Point 3

Suzetrigine Development Strategy and Timeline

It involves changes in the strategy and timeline for the development of suzetrigine, which could impact future revenue and market positioning.

Has there been any update on the potential development of suzetrigine in chronic pain? - Julian (for Paul Matteis, Stifel)

2025Q3: Focus remains on securing the DPN indication with the second DPN study planned for completion by the end of next year. Expanding into PNP is interesting, but priorities are on DPN studies and timelines. - Reshma Kewalramani(CEO)

What are your plans for the DPN trials given the decision to not pursue a broad PNP label, and whether next-generation drugs will be used to target LSR or smaller indications like small fiber neuropathy? - Salveen Jaswal Richter (Goldman Sachs)

2025Q2: Our immediate goal is to secure the DPN indication first, and then we plan to explore broadening that label, possibly to include small fiber neuropathy. - Reshma Kewalramani(CEO)

Contradiction Point 4

VX-828 Profile and Timeline

It involves differing statements about the expected profile and timeline for VX-828, which could impact future revenue and product positioning.

How many of the 170 million JOURNAVX users have unrestricted access, and when is the VX-828 data expected to be disclosed? - Edward (for David Risinger, Leerink Partners)

2025Q3: VX-828 is the most efficacious in vitro CF corrector studied and data is expected next year. - Reshma Kewalramani(CEO)

What are the expectations for the VX-828 profile? What is the number of commercial lives with unrestricted access to JOURNAVX? - David Reed Risinger (Leerink Partners)

2025Q2: For VX-828, we plan to initiate a CF cohort before the end of the year. - Reshma Kewalramani(CEO)

Contradiction Point 5

JOURNAVX Payer Coverage and Unrestricted Access

It involves the progression and status of payer coverage for JOURNAVX, which is crucial for revenue growth and market access.

How many of the 170 million JOURNAVX lives have unrestricted access, and what is the timeline for VX-828 data disclosure? - Edward(for David Risinger, Leerink Partners)

2025Q3: 113 million of the 170 million lives have unrestricted access with no prior authorization. - Duncan J. McKechnie(CMO)

Can you explain the early adopters of ALYTREK and the tiered and preferred status nuances for JOURNAVX? - Salveen Richter(Goldman Sachs)

2025Q1: We have coverage for 42 million without prior authorizations and 94 million total lives. - Duncan McKechnie(COO)