Ionis Paves Its Own Path as Initial Tryngolza Launch Defies Expectations

Why It Matters

The breakthroughs demonstrate Ionis' ability to deliver high‑value therapies and expand into larger markets, boosting its revenue potential and competitive standing in the antisense space.

Key Takeaways

• Bepirovirsen functional cure 15‑20% in Phase 3 trial.
• Tryngolza generated $102 million revenue in 2025 launch.
• Ionis plans supplemental sHTG submission, targeting broader market.
• FCS price $595k; sHTG price expected lower.
• Arrowhead's Plozasiran competes, priced around $60k annually.

Pulse Analysis

Ionis Therapeutics is redefining its market role by moving beyond a research‑centric model into full‑scale commercialization. The recent Phase 3 success of bepirovirsen, delivering a functional cure rate of 15‑20% for chronic hepatitis B, not only eclipses the modest 1‑3% outcomes of current standards but also positions the company as a pioneer in antisense‑driven curative therapies. This achievement, slated for detailed disclosure at the upcoming EASL meeting, underscores the potency of Ionis' RNA platform and its strategic partnership network, which includes GSK, AstraZeneca, Roche, and Novartis.

The launch of Tryngolza for familial chylomicronemia syndrome (FCS) further cements Ionis' commercial credentials. Generating roughly $102 million in its inaugural year, the drug’s rare‑disease pricing of $595,000 reflects the high value placed on transformative lipid‑lowering solutions. Ionis is now pursuing a supplemental submission to broaden Tryngolza’s indication to severe hypertriglyceridemia, a far larger patient pool, with expectations of a more modest price point. This expansion pits Ionis against Arrowhead Pharmaceuticals, whose competing Plozasiran is priced near $60,000 annually, highlighting a competitive pricing dynamic in the cardiometabolic arena.

Looking ahead, Ionis’ pipeline momentum extends beyond hepatitis B and FCS. The company is advancing zilganersen for Alexander disease, a rare neurodegenerative condition, and anticipates multiple Phase 3 readouts from its partnered programs throughout the year. With earnings slated for February 25, investors will scrutinize how these developments translate into sustained revenue growth and market share gains. Ionis’ ability to launch and scale high‑price, high‑impact therapies signals a broader shift toward independent biotech commercialization, potentially reshaping valuation benchmarks across the antisense sector.

Ionis Paves Its Own Path as Initial Tryngolza Launch Defies Expectations

November 10, 2025

Investors were not exactly expecting Ionis’ GSK‑partnered antisense oligonucleotide to achieve a functional cure in chronic hepatitis B. CEO Brett Monia, however, was not surprised.

“I think we made our point. I don’t think it’s seeping in well enough yet, but it will,” Monia told BioSpace on the sidelines of the J.P. Morgan Healthcare Conference in January.

Kicking off a catalyst‑rich year for Ionis, partner GSK on January 7 revealed that bepirovirsen achieved a “statistically significant and clinically meaningful functional cure rate” in a Phase 3 trial. GSK did not reveal the specific figures, only saying that the trial met its primary endpoint. The Big Pharma partner will release more details from the trial at the European Association for the Study of the Liver meeting this spring, while a new drug application will be filed in the first quarter.

Monia explained that the trial measured a functional cure rate of about 15–20 %, while existing treatments achieve maybe 1–3 %.

And last month’s bepirovirsen readout just scratches the surface of what Ionis has in store for 2026. Last year, the RNA‑interference biotech launched two products independently—Dawnzera for the prevention of hereditary angioedema attacks and Tryngolza for familial chylomicronemia syndrome (FCS).

“Ionis has been historically an R&D organization. Now we built the commercial capabilities to support the launches that occurred,” Monia said.

Ionis is planning a supplemental submission by the end of the year to expand Tryngolza into severe hypertriglyceridemia. If granted, William Blair expects the antisense drug to be “transformational” for this indication.

Tryngolza took home approximately $102 million in 2025 while Ionis has yet to report sales for Dawnzera. The launch of the former has impressed analysts so far. William Blair in January predicted that Tryngolza could reach $2 billion in sales in 2034.

Ionis also had two successful Phase 3 readouts last year, including one for Tryngolza in severe hypertriglyceridemia (sHTG). Monia said the data showed “remarkable reductions” in triglycerides. The trial, which could help support bringing the treatment into a larger disease population, helped underpin an FDA application at the end of the year.

The initial launch success in FCS is “a sign of the company’s impressive salesforce in cardiometabolic disease and auspicious for a potential launch of Tryngolza in sHTG,” William Blair wrote in a January note.

While Ionis has now launched medicines independently, the potential sHTG indication would be the first time the company has forayed into more common diseases.

In this space, Ionis is up against Arrowhead Pharmaceuticals, another mid‑sized biotech that is rising as an independent commercial company. Plozasiran was approved for FCS in November 2025 and a Phase 3 readout for sHTG is expected in the third quarter.

With the FCS approval, Monia said Ionis priced the drug for a rare indication at $595,000. The CEO promised the price would come down as it moves into a more common indication.

“Let’s face the facts: the FCS market—we pretty much created it, and we’re doing extremely well. There’s not much left for a competitor to come in,” Monia said.

The specific sHTG price has not been announced, although William Blair put the wholesale acquisition cost between $10,000 and $20,000 per year—much lower than Arrowhead’s planned $60,000 cost for the rival medicine.

Ionis also has zilganersen, which showed a disease‑modifying benefit in a Phase 3 trial of patients with the rare neurodegenerative condition Alexander disease last year. Monia said that children with the devastating disorder typically do not survive past age four. Ionis plans to file an approval application for zilganersen this quarter.

Elsewhere, Ionis’ partnered pipeline is advancing as well, with four Phase 3 readouts expected this year. In addition to GSK, the company has partnerships with AstraZeneca, Roche and Novartis, as well as a handful of smaller companies.

“It seems like [2025] was the greatest year in our history, based on all of the achievements we made and how we transformed the company,” Monia said. “And I expect to make the same claim in December of this year.”

Ionis will report earnings and provide company highlights on February 25.