Arrowhead Pharmaceuticals filed the application that turns its rare-disease drug into a business for a much larger patient group, and the FDA has put it on a faster clock.
The Pasadena company said in its fiscal 2026 results release on Thursday that it has submitted a supplemental new drug application for plozasiran in severe hypertriglyceridemia. The FDA granted the filing entry into its Split Real Time Application Review pilot, which gives it a six-month priority review instead of the standard ten months. Arrowhead said it is preparing for a U.S. launch in the second quarter of 2027, pending approval. That timetable implies a decision in the first half of the year, which is what a six-month priority review of a filing submitted in recent weeks would produce.
Plozasiran is a small interfering RNA that silences apolipoprotein C-III, a liver protein that slows the clearance of triglyceride-rich particles from the blood. It is injected under the skin once every three months. The drug is already approved as REDEMPLO for familial chylomicronemia syndrome in the United States, the European Union, Britain, Canada, China, and Australia. Severe hypertriglyceridemia is a far more common diagnosis, and it is the market where the company's commercial future sits.
Doctors treat severe hypertriglyceridemia first with diet, alcohol restriction, and control of diabetes, then with fibrates or high-dose omega-3 products. Those steps lower the number, but the evidence that they prevent pancreatitis is thin, and none of the older drugs carries an approval for that outcome. The APOC3 drugs were tested in large trials that adjudicated pancreatitis events, so the outcome is now measurable in a way the older options never allowed.
The case for the filing rests on two identical Phase 3 trials, SHASTA-3 and SHASTA-4, whose results were published in the New England Journal of Medicine on Nov. 5 and presented at the European Society of Cardiology congress in August and at the American Heart Association's scientific sessions.
The trials enrolled 757 adults with fasting triglycerides of at least 500 mg/dL at 214 sites in 24 countries. Patients were assigned 2 to 1 to 25 mg of plozasiran or placebo at baseline and again at months 3, 6, and 9. The primary endpoint was the change in triglycerides at 12 months.
At month 12, median triglycerides fell 79% in SHASTA-3 and 81% in SHASTA-4, against about 27% with placebo. The placebo-adjusted differences were 45 and 47 percentage points, both with P values below 0.001. More than 90% of treated patients in both studies finished the year below 500 mg/dL, the threshold that defines the condition, and more than half fell below 150 mg/dL, which is inside the normal range.
The pancreatitis number carries the filing
Triglyceride levels matter to patients mostly through a single risk: acute pancreatitis, an inflammation of the pancreas that can put people in the hospital and, in severe cases, kill them. For years the standard therapies lowered triglycerides without a clear record on that outcome. One severe hypertriglyceridemia drug now carries such a record on its label, and plozasiran is filing for the same.
In the pooled SHASTA analysis, plozasiran produced 1 acute pancreatitis event per 100 patient-years against 5 on placebo, a rate ratio of 0.22 and a 78% reduction, with a P value of 0.008. Among patients with a previous episode of pancreatitis, the event rate fell 91%, and among those with prior pancreatitis and baseline triglycerides between 500 and 880 mg/dL it fell 82%. In the highest-risk group, patients with prior pancreatitis and baseline triglycerides of at least 880 mg/dL, there were no events among 35 treated patients and five among 17 who received placebo.
That subgroup is small, and the company and its investigators have said so. It is also the kind of number that regulators and payers read first, because it is a clinical outcome rather than a laboratory value.
Safety was consistent with the earlier FCS program. Serious adverse events occurred in 8% of plozasiran patients and 10% of those on placebo. The most common treatment-related problem was worsening glycemic control, at 14.3% versus 8.7%, followed by diarrhea at 5.6% versus 3.2%. Discontinuations for side effects were 1.4% and 0.8%. There was no anaphylaxis in either trial, and no clinically meaningful changes in platelet counts or liver enzymes.
The trial has limits. The population was mostly White and mostly male, there was no patient-reported measure of abdominal pain, and the follow-up stopped at one year. An open-label extension is running. At 36 months of total treatment in the earlier FCS study, median triglycerides remained 76% below baseline and APOC3 89% below.
The review track matters as much as the data
The STAR program is aimed at supplemental indications for drugs that are already approved. To qualify, the FDA has to determine that the evidence from adequate and well-controlled trials may show a substantial improvement on a clinically relevant endpoint over available therapies. Entry buys a six-month priority review, and the agency generally targets an action at least a month before the goal date. It also means Arrowhead does not have to use a priority review voucher, so the voucher it bought last year stays with the company.
The designation does not promise approval. It does mean the agency has already concluded that the data may show a substantial improvement, which is the same question payers will ask when the drug reaches them. Whether the final label carries explicit language about pancreatitis is a separate decision inside that review.
That voucher appears in the financial statements. Arrowhead recorded a $215 million charge for the acquired priority review voucher, one line in a year that shows the cost of becoming a commercial company. Revenue fell to $450.8 million from $829.4 million. Research and development rose to $739.1 million from $607.2 million, and selling, general, and administrative expense rose to $202.0 million from $123.9 million as the company built a sales force for REDEMPLO.
The net loss attributable to Arrowhead was $724.2 million, or $5.11 a share, against a loss of $1.6 million a year earlier. The company ended September with $1.19 billion in cash and available-for-sale securities, up from $919 million a year earlier, and it carries $683.5 million in convertible notes alongside a $400.4 million royalty liability.
The commercial numbers for REDEMPLO are in the same release. Cumulative new-to-brand prescriptions reached 950 at the end of the quarter, with another 300 received since. The company reported 50 to 60 prescriptions a week, more than 640 prescribers at quarter end and more than 860 since, and 160 million covered lives. Those are small numbers by the standards of a primary care drug, which is the point. Familial chylomicronemia syndrome is rare, and the severe hypertriglyceridemia filing is how the fixed costs of that sales force get spread over a larger base.
The rest of the release points to the platform. Arrowhead said its dual-target RNAi candidate ARO-DIMER-PA produced reductions in PCSK9, APOC3, LDL cholesterol, and triglycerides in an early trial, and that a tau-targeting candidate lowered cerebrospinal fluid tau in healthy volunteers, which the company described as the first clinical validation of siRNA delivery across the blood-brain barrier. Those programs are years from revenue. They are also why the company presents itself as a platform rather than a single drug, and why investors will read the sHTG launch as a test of how far that platform can carry a commercial organization.
Ionis got there first, and cheaper
The market plozasiran is filing into already has an approved product with the same target. Ionis Pharmaceuticals won FDA approval for Tryngolza, or olezarsen, in severe hypertriglyceridemia on June 24. The label covers reduction of triglycerides and of the risk of acute pancreatitis in adults with the condition, making it the first therapy approved to reduce that risk.
Olezarsen is an antisense oligonucleotide given once a month at 50 or 80 mg. Its CORE and CORE2 trials found acute pancreatitis reductions of 91% at the 50 mg dose and 76% at 80 mg, or 85% pooled, with a rate ratio of 0.15. At 12 months, 86% of treated patients had triglycerides below 500 mg/dL. The placebo-adjusted triglyceride reductions were smaller than plozasiran's, roughly 49% to 72% depending on dose.
Four injections a year against twelve is a difference a pharmacy benefit can see, even before anyone measures whether patients stay on either drug.
Then there is price. Tryngolza launched at $595,000 a year and Ionis cut the list price to $40,000 in April. Arrowhead launched REDEMPLO at $60,000 and later cut its wholesale acquisition cost to $45,000, a figure the company has said will stay the same across FCS and severe hypertriglyceridemia if the larger indication is approved. The two drugs now sit within $5,000 of each other on list price, which turns the competition into a fight over labels, dosing schedules, and payer contracts rather than a fight over who can undercut whom.
What the next year decides
Two drugs aimed at the same protein and the same diagnosis, one with a pancreatitis claim already on its label and one asking for the same, will be compared in ways their separate trials cannot settle. Cross-trial comparisons are unreliable. The SHASTA program enrolled a different population from CORE, used a different dosing schedule, and measured events over a different period. Plozasiran lowered triglycerides further. Olezarsen reached the market first and has a label that explicitly names pancreatitis risk.
Payers will weigh the labels and the net prices, not the mechanisms. Doctors will weigh a quarterly injection against a monthly one, and the record Olezarsen has built in this population against the one Arrowhead is about to start. The FDA's review will decide what Arrowhead can claim. The launch will decide whether the claim is enough.
Arrowhead's chief executive, Christopher Anzalone, described the company as one that is now beginning to translate promise into real patient outcomes. That is a fair summary of the fiscal report. It is also the standard the severe hypertriglyceridemia launch will be held to, and the competitor selling into the same patients will have close to a year's head start.
Primary sources
- Arrowhead Pharmaceuticals, fiscal 2026 results press release, Exhibit 99.1 to Form 8-K, Nov. 12, 2026.
- Watts GF et al., "Plozasiran for Severe Hypertriglyceridemia and Risk of Pancreatitis," New England Journal of Medicine, Nov. 5, 2026.
- HCPLive, "FDA Approves Olezarsen (Tryngolza) for Severe Hypertriglyceridemia," June 24, 2026.
- The Motley Fool, Arrowhead Pharmaceuticals Q2 2026 earnings call transcript, May 8, 2026.