After 35 years engaged in the research and development of pharmaceutical products, Ionis began marketing its drugs for the first time in 2024.
While the company’s maiden voyage into commercialization has progressed “remarkably smoothly,” according to CEO Brett Monia, Ph.D., those efforts will now ratchet up to a new level with the FDA approval of Tryngolza to treat severe hypertriglyceridemia (sHTG).
With the nod, Ionis advances from selling two rare disease drugs to marketing a product that could be used by millions of potential patients.
There is no other drug on the market designed specifically to treat sHTG or to combat its accompanying bouts with pancreatitis, which can land patients in the hospital for extended stays and be life threatening.
“The treatments today for sHTG are generics that are grossly inadequate,” Monia said in an interview earlier this week. “Fish oils have a modest 10 to 20% reduction in triglycerides (TG). But what we’re achieving, on top of those medicines, is up to a 72% reduction.”
That 72% reduction, compared to placebo, was seen at six months in a phase 3 trial in patients who received an 80-mg monthly injection of Tryngolza. For those who were given a 50-mg injection, the mean reduction was 63%.
In another trial of those with lower TG levels, the reductions were 55% and 49% versus placebo for the 80-mg and 50-mg groups, respectively.
As a secondary endpoint, the two trials demonstrated that Tryngolza can reduce the risk of pancreatitis by 85%, “which has never been shown before,” Monia said.
Of the 1,086 patients in the trials, 86% achieved TG levels below 500 mg/dL, which is a key threshold for reducing acute pancreatitis risk. Additionally, 54% of patients achieved normal TG levels. These reductions came despite patients remaining on lipid-lowering treatments throughout the studies.
Tryngolza, which is an apoC-III antisense oligonucleotide (ASO), was originally approved in December of 2024 to treat a rare form of sHTG called familial chylomicronemia syndrome (FCS). The launch in that indication has progressed well, with sales reaching $108 million last year.
In April, bolstered by the growing confidence in its prospects in sHTG, Ionis increased its peak net sales projection for Tryngolza from $2 billion to $3 billion.
The latest FDA endorsement is for Tryngolza to be used along with diet to reduce the fatty cells in the blood that can trigger pancreatitis attacks, which cause debilitating abdominal pain.
Once an attack occurs, a patient becomes more susceptible to another as it causes permanent damage to the pancreas. Severe hypertriglyceridemia also brings increased risk of cardiovascular problems.
There are an estimated 3.6 million in the U.S. with sHTG, defined as those who have TG levels above 500 mg/dL. But Ionis is initially focusing on patients who are at a higher risk for acute pancreatitis, those with levels above 880 mg/dL, Monia said. There are roughly 500,000 in the U.S. who fall into this category.
In anticipation of the approval, Ionis’ launch team has been in place since February, promoting Tryngolza to endocrinologists, cardiologists and lipid specialists for FCS while also educating them on sHTG.
“The physicians are just chomping at the bit, waiting to prescribe Tryngolza for their sHTG patients since they manage so many of them,” Monia said.
“These patients are already recognized. It’s not like a rare disease that we have to educate physicians on what to look for. They’re already treating them. They’re just not treating them adequately,” Monia added.
At the start of April, Ionis took the unusual step of slashing the annual list price of Tryngolza from $595,000 to $40,000 to “support timely and sustained patient access.”