Ionis’ Tryngolza (olezarsen) is set to become the company’s first wholly owned blockbuster drug, CEO Brett Monia believes.
Speaking at the J.P. Morgan Healthcare Conference, taking place in San Francisco from 12 to 15 January, Monia said that the company has increased peak revenue forecasts based on Tryngolza’s potential to be approved in a new indication.
While the drug has already received approval for familial chylomicronemia syndrome (FCS), Ionis submitted a New Drug Application (NDA) to the US Food and Drug Administration (FDA) in late December 2025 and had requested Priority Review for the drug in severe hypertriglyceridemia (sHTG).
The NDA has been submitted based on the CORE-1 and CORE-2 trials (NCT05079919 and NCT05552326), in which the drug led to what Ionis deemed “groundbreaking” changes. In the trials, there was a 72% placebo-adjusted mean reduction in fasting triglyceride levels at six months, with reductions sustained through 12 months.
86% of Tryngolza-treated patients achieved triglyceride levels less than 500 mg/dL, below the risk threshold for acute pancreatitis and more than half returned to a normal range of triglyceride. As well as this, the event rate of acute pancreatitis reduced by 85%.
Treatment options currently for sHTG remain limited, Monia said, with standard of care (SoC) therapies and lifestyle modifications not sufficiently or consistently assisting in lowering triglyceride levels or reducing the risks of sHTG in all patients.
The drug gained approval in FCS in December 2024, with Monia stating that in 2025, sales of the drug reached an estimated $105m. With the success in sHTG, the company has increased its annual peak product revenue opportunity from $1bn to $2bn.
Also revealed by Monia in the session at J.P. Morgan is that five Phase III readouts are anticipated in 2026. One of these has already been announced, with its GSK-partnered drug bepirovirsen, which showed benefit in patients with chronic hepatitis B (CHB).
Other pipeline candidates include zilganersen in Alexander disease, pelacarsen in lipoprotein A cardiovascular disease (Lp(a) CVD), eplontersen in transthyretin-mediated amyloidosis with cardiomyopathy (ATTR-CM), sefaxersen in IgA nephropathy (IgAN), and ION582 in Angelman syndrome. Ionis anticipates launches of all these drugs by the end of 2028.
As well as Tryngolza in sHTG, Ionis is also hoping to gain approval of bepirovirsen and zilganersen in 2026.
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