Vertex Pharmaceuticals (NASDAQ:VRTX) management emphasized revenue growth, expanding product diversification, and multiple late-stage pipeline milestones while reviewing fourth-quarter and full-year 2025 results on its earnings call. Executives highlighted continued strength in cystic fibrosis (CF), momentum for CASGEVY in sickle cell disease and transfusion-dependent beta thalassemia, a rapidly growing foundation for JOURNAVX in acute pain, and a developing renal franchise led by povetacicept.
Financial performance and 2026 guidance
Vertex reported fourth-quarter 2025 total revenue of $3.2 billion, up 10% year-over-year, and full-year revenue of $12.0 billion, up 9% versus 2024. Non-GAAP net income in the fourth quarter was $1.3 billion, up 24%, with earnings per share of $5.03, up 26%. For full-year 2025, non-GAAP net income was $4.7 billion and EPS was $18.40.
Vertex ended 2025 with $12.3 billion in cash, cash equivalents, and marketable securities. The company repurchased about 4.8 million shares for roughly $2 billion during 2025.
For 2026, Vertex guided to total company revenue of $12.95 billion to $13.1 billion, representing 8% to 9% growth. The outlook includes $500 million or more from non-CF products, reflecting expectations for higher CASGEVY infusion volumes and a ramp in JOURNAVX prescriptions. Management also guided to combined non-GAAP operating expenses of $5.65 billion to $5.75 billion and a non-GAAP effective tax rate of 19.5% to 20.5%, noting 2025 benefited from one-time tax credits that are not expected to repeat. The company said it does not expect tariffs to have a material impact based on its supply chain and U.S. manufacturing footprint, though the outlook could change.
Commercial updates: ALYFTREK, CASGEVY, and JOURNAVX
Chief Commercial Officer Duncan McKechnie said 2025 was focused on executing multiple launches, including ALYFTREK in the U.S. and Europe, CASGEVY across the U.S., Europe, and the Middle East, and JOURNAVX in the U.S. He said more than 77,000 patients are on one of Vertex’s CF therapies and that the company has access agreements in more than 60 countries.
On ALYFTREK, McKechnie said the rollout in the U.S. and Europe was progressing well, with most treatment-naive patients in reimbursed countries already on ALYFTREK. He added that the majority of ALYFTREK prescriptions continue to come from patients switching from TRIKAFTA, and that improved sweat chloride results and once-daily dosing are resonating with clinicians, even as Vertex sees “strong patient loyalty” to TRIKAFTA. He said the fourth quarter benefited from international launch contributions after reimbursement wins in Europe and expected that momentum to continue in 2026. In Europe, he cited reimbursed access in England, Ireland, Germany, Denmark, and Norway, and noted new reimbursement in Australia, New Zealand, and Italy, which he said enables access for about 1,500 patients to a CFTR modulator for the first time.
For CASGEVY, McKechnie described 2025 as a year of “significant momentum.” In fourth-quarter 2025 results, CASGEVY posted 111 new patient initiations, 37 first cell collections, and 30 infusions, contributing to $54 million in quarterly revenue. For full-year 2025, CASGEVY revenue was $116 million. He cited reimbursement developments including participation by more than 30 U.S. states in the CMS Cell and Gene Therapy Access Model and “approximately 90% access” for Medicaid and commercial patients, with the remainder handled case by case. In Europe, he said all U.K. countries provide reimbursed access, and he pointed to an Italian coverage decision representing about 5,000 eligible transfusion-dependent beta thalassemia patients. Management cautioned that CASGEVY infusions could be variable quarter to quarter in 2026 due to the duration of the treatment journey and because patients dictate infusion timing, with smoothing expected in 2027 and beyond as patient backlogs build.
JOURNAVX revenue was $27 million in the fourth quarter and $60 million for full-year 2025, reflecting eight months of sales since launch, according to CEO Reshma Kewalramani. McKechnie said more than 550,000 JOURNAVX prescriptions were filled in 2025 with an approximately 50/50 split between hospital and retail channels, and that the fourth quarter alone matched the combined prescriptions of the first three quarters. He attributed a lag between prescription growth and revenue growth to the company’s patient support program, which impacted gross-to-net in 2025. McKechnie said more than 35,000 physicians prescribed JOURNAVX in 2025 and that more than 200 million lives now have access across all three national pharmacy benefit managers. He also said 21 states provide unrestricted Medicaid access without prior authorization or step edits, and that JOURNAVX has been incorporated into formularies, order sets, and/or discharge protocols across more than 950 hospitals and more than 100 integrated delivery networks.
Looking ahead, Vertex plans to double the JOURNAVX field force in the second quarter of 2026 and continue consumer engagement, including a TV campaign launched in January and piloted in select markets. McKechnie said Vertex expects to more than triple JOURNAVX prescriptions in 2026 versus 2025, and that as the patient support program sunsets and gross-to-net normalizes in late 2026 and early 2027, prescription growth should translate more directly into revenue growth.
R&D progress: CF expansion and next-generation programs
Kewalramani described ALYFTREK as a “next generation 2.0 CFTR modulator” and Vertex’s fifth approved CF therapy, citing once-daily dosing, broader mutation coverage, and what she called the best CFTR protein function restoration in the company’s portfolio.
Vertex shared top-line results from a completed Phase 3 ALYFTREK study in two- to five-year-old patients who switched from TRIKAFTA upon entry. Kewalramani said ALYFTREK was safe and well tolerated, and that sweat chloride showed a mean reduction of 9.6 mmol from a TRIKAFTA baseline. She added that 65% of patients achieved sweat chloride below 30 mmol at 24 weeks, compared to 37.5% at baseline on TRIKAFTA. Vertex said it expects to initiate global regulatory submissions for ALYFTREK in the two- to five-year-old age group in the first half of the year, and noted that a one- to two-year-old study has begun enrollment and dosing.
On the next wave of CFTR modulators (next-gen 3.0), Vertex said VX-828 is in a proof-of-concept study expected to complete enrollment and dosing in the first half of 2026, and VX-581 is in a Phase 1 healthy volunteer study. For patients who do not produce CFTR protein, Vertex said its Phase 1/2 study of VX-522 is on track for a readout in the second half of the year.
Renal franchise: povetacicept, inaxaplin, and VX-407
Management positioned renal as an emerging “fourth vertical” alongside CF, hematology, and pain. Kewalramani said povetacicept (a dual BAFF/APRIL inhibitor) is the most advanced renal asset, with the first expected indication in IgA nephropathy (IgAN). She said povetacicept has FDA breakthrough therapy designation and is progressing through a BLA pathway with rolling review. Vertex used a priority review voucher and submitted the first BLA module in December 2025, and said it expects to complete the BLA submission in the first half of the year if Phase 3 interim results are supportive.
In Q&A, Kewalramani addressed questions about hypogammaglobulinemia risk, saying IgG decreases are part of the BAFF/APRIL mechanism, but she cited RUBY-3 80 mg cohort data presented at ASN in November that showed no serious adverse events and no serious infections, including among patients at lower IgG levels. She said the average IgG level in RUBY-3 was within the normal range and stated she did not see a concern when weighing overall benefit-risk.
On efficacy expectations, Kewalramani pointed analysts to RUBY-3 as an analog for the Phase 3 RAINIER interim analysis, noting similarities in design, entry criteria, dose (80 mg), and endpoint. She cited a 56% reduction in proteinuria at 36 weeks in RUBY-3 and characterized proteinuria reductions as important for long-term outcomes over chronic treatment. She also noted that RAINIER is placebo-controlled while RUBY-3 was not, and relayed a view expressed by an IgAN expert that placebo proteinuria improvement could be roughly 0% to 5% over the interim timeframe.
McKechnie said Vertex began engaging payers in July and has had 74 engagements covering more than 210 million lives, describing those conversations as going “extremely well.”
Beyond IgAN, Vertex said povetacicept is being studied in membranous nephropathy in the OLYMPUS Phase 2/3 adaptive study, which is enrolling and dosing; Vertex expects to complete the Phase 2 portion and advance to Phase 3 in the summer. Kewalramani also reiterated plans to initiate a Phase 2 dose-ranging proof-of-concept study of povetacicept in generalized myasthenia gravis in the first half of 2026.
Vertex also reviewed inaxaplin for APOL1-mediated kidney disease (AMKD), noting completion of enrollment in the interim analysis cohort of the AMPLITUDE pivotal study last fall. The company expects to complete enrollment in the full cohort in the second half of the year, with interim cohort results late this year or early next year, and said it could file for U.S. accelerated approval if results are positive. Kewalramani said she expects Phase 3 results to be “very similar” to Phase 2, while noting the Phase 3 primary endpoint is GFR slope and that the FDA pathway to accelerated approval is based on 48-week GFR.
Finally, Vertex said VX-407 is in a Phase 2 proof-of-concept trial for autosomal dominant polycystic kidney disease (ADPKD), with enrollment expected to complete this year. The study will evaluate height-adjusted total kidney volume, which the company said is an FDA-accepted surrogate endpoint in ADPKD.
About Vertex Pharmaceuticals (NASDAQ:VRTX)
Vertex Pharmaceuticals Inc is a Boston-based biotechnology company focused on the discovery, development and commercialization of therapies for serious diseases. Founded in 1989, Vertex built its reputation on research-driven drug development and is best known for its work in cystic fibrosis (CF), where its portfolio of small-molecule CFTR modulators transformed standards of care for many people with the disease. The company operates research and development, manufacturing and commercial organizations and serves patients and healthcare systems in multiple international markets.
Vertex’s marketed products center on CFTR modulators that target the underlying cause of cystic fibrosis rather than just treating symptoms.
