Ionis Pharma’s regulatory and launch preparations for lead investigational compound olezarsen are proceeding to plan, the company said Monday after sharing positive Phase 3 data.

Olezarsen is designed to treat familial chylomicronemia syndrome (FCS), a roughly one-in-a-million disease which causes patients’ triglycerides (TGs) to soar to very high levels, often leading to a potentially fatal condition called pancreatitis. With no approved treatment, it’s a disease of severe unmet need.

“We are right where we should be in preparing to launch olezarsen for the treatment of FCS, our first independent launch as a fully integrated commercial organization,” said Jonathan Birchall, Ionis chief commercial officer, on a call with analysts Monday morning.

Ionis plans to submit a new drug application this year and, assuming priority review and approval, a U.S. launch is possible by year’s end. The agent has breakthrough therapy and orphan drug designations.

During the trial, investigators saw dose-dependent reductions in subjects’ TGs, as well as in ApoC-III, a liver protein that regulates TGs, at six and 12 months. The study, dubbed Balance, also showed a clinically meaningful reduction in acute pancreatitis events — one event each in the 50-mg and 80-mg arms, versus 11 events across seven placebo patients. 

In addition, the time to the first event took longer with olezarsen, leading to an 84% reduction in all-cause hospitalizations at one year.

Balance is the first clinical study to validate that reducing TG levels can lead to a meaningful reduction in acute pancreatitis, noted Brett Monia, Ionis CEO. That association “increases our confidence that, if approved, olezarsen will become the standard of care for FCS.”

Consistent with topline data, there were no drug-related serious adverse events. More adverse events were reported in the placebo group, although one non-drug related death occurred in the olezarsen arm. 

The full data, which were presented Sunday during the 2024 American College of Cardiology (ACC) annual meeting and appeared simultaneously in the NEJM, were largely in line with expectations following last year’s topline of the FCS program. 

Perhaps more importantly, they also read through positively to a larger opportunity Ionis is eyeing for using olezarsen in patients with severe hypertriglyceridemia (sHTG), which numbers three million patients in the U.S. At ACC, Ionis shared primary results of its Phase 2b Bridge-TIMI 73a trial in patients with sHTG at high cardiovascular risk. 

Olezarsen was associated with placebo-adjusted TG reduction of 49.3% and 53.1%, respectively, in the 50-mg and 80-mg trial arms, with greater reduction in patients whose TG levels were above 500 mg/dL, which is representative of sHTG. Although a small number of subjects (16) who met the sHTG criteria makes readthrough imperfect. Ionis expects to share Phase 3 data next year. 

Meanwhile, the company’s olezarsen launch plans continue apace. Earlier this year, the firm re-hired former chief commercial officer Kyle Jenne as EVP, chief global product strategy officer, to lead all aspects of commercialization. That followed the departure of Onaiza Cadoret-Manier, former chief global product strategy and operations officer.

During his prior stint as Ionis CCO, Jenne played a key role in establishing the co-commercialization collaboration with AstraZeneca for Wainua (eplontersen). Ionis’ first branded medicine, Wainua, launched earlier this year in hereditary transthyretin amyloidosis polyneuropathy (hATTR-PN).

“Leveraging the capabilities we have developed for the launch of Wainua, we are also building a world-class patient and caregiver support team to help patients through every step of their treatment journey,” said Birchall. 

Expecting first-mover advantage in FCS, the company has also been executing on its patient-, physician- and payer-focused launch strategy. A field medical team has been out contacting physicians for nearly three years, building disease awareness and urgency to treat through education on identifying and ultimately diagnosing FCS, Birchall noted.

“We’ve conducted extensive market research to identify the physicians most likely to diagnose FCS and treat patients with olezarsen, assuming approval,” he said. “These are the physicians we will focus on most after launch, and using omnichannel capabilities we will extend our launch efficiently to reach a broader pool of potential treating physicians.”

This summer, Birchall added, the firm plans to hire its customer-facing sales team. 

Asked during the call what payers may require, he added, “From a payer perspective we know, given certainly some of the clinical outcomes you heard today from Balance and some of the economic impact that acute pancreatitis has on the hospital data, that this is meaningful for payers. And our market research is overwhelming that they’re supportive of covering olezarsen as a treatment for a rare disease.”