Ionis Pharmaceuticals (NASDAQ:IONS) executives used the company’s fourth-quarter and full-year 2025 earnings call to highlight what CEO Brett Monia called a “defining year,” pointing to the successful execution of its first two independent commercial launches, multiple positive late-stage readouts, and a financial performance that exceeded guidance.
Commercial launches: TRYNGOLZA ramps in FCS; DAWNZERA begins switching patients in HAE
Ionis said TRYNGOLZA, the first FDA-approved treatment for familial chylomicronemia syndrome (FCS), exceeded the company’s expectations in its first year. Chief Global Product Strategy Officer Kyle Jenne reported fourth-quarter net product sales of $50 million, up 56% sequentially, and full-year TRYNGOLZA revenue of $108 million. Jenne noted that December was the strongest month of 2025, and that approximately 75% of prescriptions came from specialists such as cardiologists, endocrinologists, and lipidologists.
Ionis’ second independent launch began in August with FDA approval of DAWNZERA, a prophylactic treatment for hereditary angioedema (HAE). Monia described it as the first and only RNA-targeted medicine for HAE, and said it has a profile resonating with prescribers and patients. Jenne said early adoption has included patients switching from other prophylactic therapies, patients previously using on-demand therapy only, and treatment-naive patients. He also cited “100% conversion to paid therapy to date” from the free trial program and reaffirmed peak sales potential “in excess of $500 million.”
Ionis also highlighted European progress for both assets, noting TRYNGOLZA launched in Europe late in 2025 via partner Sobi, while DAWNZERA received European approval last month with Otsuka set to commercialize it across the region.
Pipeline updates: Olezarsen sHTG filing, Alexander disease NDA, and multiple partnered catalysts
Ionis’ leadership repeatedly returned to olezarsen, citing phase 3 data in severe hypertriglyceridemia (sHTG) from the CORE and CORE2 trials. Chief Development Officer Holly Kordasiewicz said olezarsen achieved placebo-adjusted mean triglyceride reductions of up to 72% at six months and a highly statistically significant 85% reduction in adjudicated acute pancreatitis events. She also emphasized the “number needed to treat” metric: in the highest-risk subgroup, four patients treated for 12 months to prevent one acute pancreatitis attack.
The company said the FDA granted breakthrough therapy designation and that it submitted a supplemental NDA late in 2025. Executives said the filing remains in the FDA’s review window, and Ionis has requested priority review. Management said it believes priority review is warranted but emphasized it cannot speak for the agency. Ionis stated it expects a decision “shortly” on priority review and said it is planning to be launch-ready by June.
Ionis also discussed zilganersen for Alexander disease, describing it as the first medicine to demonstrate a disease-modifying benefit in the rare neurodegenerative disorder. Management said it submitted the NDA in January and anticipates potential approval and launch in the second half of 2026. The company has initiated an expanded access program while the review is ongoing. In Q&A, Ionis said there are approximately 300 people living with Alexander disease in the U.S. today and estimated about half have been identified. The company reiterated guidance of greater than $100 million in peak revenue for zilganersen.
On partnered programs, Monia pointed to positive phase 3 top-line data for GSK’s bepirovirsen in chronic hepatitis B, which he said showed “clinically meaningful and unprecedented functional cure rates.” Ionis said GSK is preparing global regulatory submissions and expects to begin bringing the drug to patients later this year, assuming approvals. Management said GSK plans to present phase 3 data at EASL in May.
Ionis also reiterated upcoming outcome-trial readouts and partnered phase 3 catalysts, including the pelacarsen Lp(a) HORIZON trial mid-year and eplontersen’s CARDIO-TTRansform trial in the second half of 2026, along with expected later-2026 readouts for sofosersen in IgA nephropathy and ulefnersen in FUS-ALS.
2025 financial results and mix shift toward commercial revenue
CFO Beth Hougen reported 2025 revenue of $944 million, up 34% year over year. Revenue included $436 million from commercial products (46% of total) and $508 million from R&D collaborations (54%). Royalty revenue increased 11% to $285 million, which Hougen said was anchored by Spinraza and growing royalties from Waylivra.
Hougen also said R&D revenue rose more than 20% year over year, with the “largest contributor” being a one-time sapablursen license fee. She said non-GAAP operating expenses rose “modestly” year over year, driven primarily by investments supporting the TRYNGOLZA and DAWNZERA launches and preparations for the planned sHTG launch.
2026 guidance: lower reported revenue due to one-time item, and sHTG timing uncertainty
For 2026, Ionis guided to total revenue of $800 million to $825 million from “numerous sources.” Hougen said this implies approximately 20% growth on an “apples-to-apples” basis after adjusting for the one-time $280 million sapablursen license fee in 2025.
The company’s guidance assumes a standard review for olezarsen’s sHTG sNDA, which would imply a potential fourth-quarter approval and limited in-year sHTG revenue contribution. Management said guidance could improve if the FDA grants priority review. Because the olezarsen filing had not yet been accepted at the time of the call, Ionis said it plans to provide TRYNGOLZA and DAWNZERA product-level revenue guidance with first-quarter results.
Hougen said Ionis expects a “meaningful decline” in TRYNGOLZA revenue during 2026 ahead of the sHTG launch as the company engages with payers to maintain broad FCS access, followed by accelerating growth if sHTG approval occurs. For DAWNZERA, Ionis expects product sales to “meaningfully contribute” to commercial revenue growth, while noting that HAE is primarily a switch market and patient conversion may take time.
Ionis also discussed milestones, saying it had already earned $65 million in the quarter-to-date period referenced on the call, including $15 million tied to European approval of DAWNZERA and $50 million when Roche initiated a phase 1 Alzheimer’s trial for an investigational medicine. The company said it is eligible for additional milestone payments related to phase 3 initiations and regulatory progress for programs including bepirovirsen and pelacarsen.
Expenses, balance sheet, and cash flow target
Hougen projected 2026 operating expenses would rise in the low-teens percentage range versus 2025, with revenue expected to grow faster than expenses to improve operating leverage. Ionis expects R&D expenses to remain steady as it redeploys resources after some late-stage studies complete.
The company forecast a 2026 non-GAAP operating loss of $500 million to $550 million, describing it as similar to 2025 after excluding the one-time sapablursen license fee and assuming a standard olezarsen review timeline. Ionis also projected ending 2026 with about $1.6 billion in cash and investments, reflecting, among other items, $433 million earmarked to repay remaining 2026 convertible notes and inventory build for a potential sHTG launch.
Management reaffirmed its goal of reaching cash flow breakeven by 2028, with Monia concluding that Ionis’ launch execution, late-stage pipeline cadence, and partnered portfolio position the company for multiple catalysts across 2026.
About Ionis Pharmaceuticals (NASDAQ:IONS)
Ionis Pharmaceuticals, Inc is a biotechnology company focused on the discovery and development of RNA-targeted therapies designed to modulate gene expression. The company’s proprietary antisense oligonucleotide (ASO) technology enables the selective binding of short synthetic strands of nucleic acids to messenger RNA (mRNA), thereby inhibiting or altering the production of disease-causing proteins. Ionis’ pipeline spans a range of therapeutic areas, including neurological disorders, cardiovascular conditions, metabolic diseases and rare genetic disorders.
Since its founding in 1989 by Dr.
