Vertex Pharmaceuticals Incorporated Q4 FY2025 earnings call

Key Points:

• 2025 was marked by excellent progress with 10% Q4 revenue growth and 9% full year growth. KASJEVY and GERNAVIX had strong launches.
• In cystic fibrosis, ElefTrex Phase 3 trial in 2-5-year-olds showed significant sweat chloride reduction, with plans for global regulatory submissions. NextGen 3.0 CFTR modulators like VX 828 and VX 581 are in development.
• Renal pipeline: POVI in IgA nephropathy and membranous nephropathy, enaxaplin in AMKD, and VX 407 in ADPKD are in various stages of clinical development.
• Commercial highlights: CF growth from new patients, launches, and geographies; KASJEVY reimbursement progress; GERNAVIX met launch objectives with over 550,000 prescriptions in 2025; renal commercialization plans underway with focus on patient access and disease education.

Vertex Pharmaceuticals saw strong financial performance in 2025. Fourth quarter total revenue was $3,200,000,000, a 10% increase from Q4 2024. Full year 2025 total revenue was $12,000,000,000, a 9% increase. For the cystic fibrosis segment, there was 7% global growth in 2025, with US CF revenue growing 11% due to pediatric uptake. KASJEVY generated $116,000,000 in revenue for the full year 2025 in the 8 months since launch. GERNAVIX had $60,000,000 in full year 2025 revenue in the 8 months since launch, with over 550,000 prescriptions filled in 2025. The renal franchise is emerging, with POVI in development for IgA nephropathy, enaxaplin in AMKD, and VX 407 in ADPKD.

Vertex expects full year 2026 total company revenue to be in the range of $12,950,000,000 to $13,100,000,000, representing 8% to 9% growth versus the prior year. This outlook anticipates continued solid performance from the CF franchise and a $500,000,000 or greater revenue contribution from non-CF products. Combined non-GAAP operating expenses are expected to be in the range of $5,650,000,000 to $5,750,000,000.

Potential risks include hypogammaglobulinemia associated with BAFF/APRIL inhibitors and how it may impact labeling. Variability in clinical trial results, such as differences in placebo rates and standard errors, could also pose risks. Additionally, the impact of tariffs and changes in payer reimbursement dynamics are areas of concern.

Q: Curious how you view the risk of potential hypogamma adverse events and how this could ultimately impact the label, if at all?

A: On hypogammaglobulinemia, the data from RUBY-3 shows no serious adverse events or infections, and average IgG levels were within normal range. The overall benefit-risk profile looks very good.

Q: With regard to the guidance here, is there any way you could help us understand what is baked into the guide for the CF component relative to Aliftrex and on Aliftrex in particular, you had a strong quarter. So walk us through the contributing factors here as we think of the trajectory for 2026?

A: Total revenue guidance includes a contribution from non-CF products. Within CF, international launch of Aliftrex in countries like the UK, Germany, etc., helped drive numbers, and this is expected to continue in 2026.

Q: With regard to Povi, can we talk about what you are expecting to show on proteinuria? Like what results do you think would provide medically, clinically differentiated data versus competitors?

A: Magnitude of proteinuria response is important, with deep proteinuria reduction being beneficial for long-term outcomes. Results from RUBY-3 80 mg IgAN study show 56% reduction in proteinuria, which is meaningful clinically.

Q: I would love for you to expand on the rationale to study Povi in gMG. Just seems to be a more crowded rare disease. I would love for you to just touch on what differentiates this asset, what you saw potentially in earlier studies, and how you think it would compare to both assets that have been approved and are under investigation for the indication?

A: Povi is a differentiated asset with a compelling mechanism of action for generalized myasthenia gravis (gMG), targeting B cell-mediated disease. Earlier studies show potential, and it is expected to have best-in-class potential compared to existing treatments.

Q: Can you remind us how to think about what rates of ADA are possible, either absolute rates or neutralizing rates? And do you expect that to be of any material number given it is a chronic drug that could be something to think about?

A: In biologics, anti-drug antibodies (ADAs) are to be expected. If they do not have a consequence on efficacy, they are not a major concern. Neutralizing antibodies would need to be monitored, but data from RUBY-3 shows no serious issues related to ADAs Q: How do you see the mix between retail and hospital setting evolving over the course of the year? And how should we think about how that mix could impact gross-to-net as well as treatment duration?

A: The mix is expected to move more towards retail proportionally. The impact on gross-to-net depends on factors like prescription length, patient type (commercial, Medicaid, self-pay), and whether they go through patient support programs.

Q: I was wondering, Reshma, if you can comment at all about the blinded serious data you are seeing from the RAINIER study at this point. And then the second one was on the WuXi deal. I know you mentioned you are developing this TCE for B cell–mediated autoimmune conditions. Wondering how you think about differentiation there on the portfolio in terms of where you might carve out those indications relative to Povi?

A: The independent data safety monitoring committee for RAINIER has given the study a clean bill of health. Details on the WuXi deal's indications are kept under wraps for now, but the tri-specific TCE is seen as complementary to Povi's pipeline-in-a-product approach for B cell–mediated diseases.

Q: Looking at the RUBY-3 UPTR data, Povi had a much larger standard error than the test receptors in their comparable studies. Any comment on what may have caused this variability? And, second, as I said, in cipaprevimab's Phase 3 studies showed very different placebo rates in their UPCR interim analysis. What is your assumption for the placebo rate in the RAINIER interim?

A: The placebo rate assumption is around 0% to 5% based on expert opinion. Variability in standard error could be due to sample size and lab test differences. On the standard error, specific causes aren't easily determined without more context.

Q: Want to ask about the $500,000,000 guidance for products outside of CF. First, could you give us some sense of the breakdown between KESJEVRI and Genomics in that number? And then second, that is a big increase, a threefold increase over 2025 and an approximate doubling versus the Q4 run-rate. What gives you confidence in that level of growth? Is it KASJEVY infusions, KASJEVY self-harvest that are happening? Visibility from payers on Genrex? Can you give us some sense of what you are seeing to put that number out there?

A: Guidance includes contribution from non-CF products. KASJEVY had strong performance with patient initiations and cell collections, providing visibility for growth. GERNAVIX's prescriptions are expected to triple in 2026, with greater access leading to revenue conversion. Confidence comes from strong launch trajectories and market visibility for these products.