As FDA approves RNAi drug, Arrowhead Pharma begins price war with rival Ionis
An RNA drug from Arrowhead Pharmaceuticals has passed regulatory standards to treat a disease that causes dangerous levels of fat in the blood, marking the company's first FDA approval and its second product approval for the rare metabolic disease in the past year. Although Arrowhead's genetic drug ranks No. 2 on the market, the biotech aims to differentiate itself from rival Ionis Pharmaceuticals with a commercialization strategy that highlights key differences for patients and payers in this disease and future indications.
The indication covered by Tuesday's FDA regulatory decision is familial chylomicronemia syndrome (FCS), a genetic disorder that causes extremely high levels of triglycerides, a type of fat, in the blood. Arrowhead's drug, in development as plozasiran, will be commercialized under the Redemplo brand name.
FCS results from impaired function of enzymes important in triglyceride metabolism. The disease affects about 6,500 people in the United States and causes fatigue, severe brain fog and recurring abdominal pain. The most serious complication of FCS is sudden inflammation of the pancreas, called acute pancreatitis. About 93% of those incidents involved hospitalization; the average length of stay was 10 days, Arrowhead said in an investor presentation. The cost of each episode of pancreatitis is estimated at $60,000.
The standard approach to controlling FCS is to limit fat intake. The FDA's approval of Redemplo for adult treatment still requires patients to maintain a low-fat diet, but the drug brings a genetic approach to the disease. Arrowhead's RNA interference (RNAi) drugs use small interfering RNA (siRNA) to inhibit the production of disease-causing proteins. Redemplo is specifically designed to inhibit the production of apoC-III, a liver protein that increases triglyceride levels by slowing the breakdown and clearance of these fats.
The FDA's decision on Redemplo was based on results from a placebo-controlled Phase 3 study whose primary objective was to measure the percent change in fasting triglycerides from baseline to month 10. The results showed that the median change in the treatment group was 59% compared with the placebo group. The most common adverse reactions in the study included hyperglycemia, headache, nausea, and injection site reactions. Detailed results were published last year in the New England Journal of Medicine and Distribution.
The first FCS drug to reach patients was Ionis' Tryngolza, which was approved by the FDA in December. Tryngolza belongs to a different class of genetic drugs called antisense oligonucleotides, which reduce levels of the same liver proteins targeted by the Arrowhead drug. While both Tryngolza and Redemplo are self-administered by patients via an auto-injector, Arrowhead's drug is less burdensome to inject every three months than Ionis's monthly injections. Arrowhead also claims an edge of safety, with no warnings or contraindications listed on its label. In contrast, the Tryngolza label warns about the risk of allergic reactions, which was the most common reason patients stopped treatment in clinical trials of the drug.
Pricing is perhaps the most obvious area of comparison between the two drugs. As the first FCS therapy, Tryngolza comes with a hefty price tag: wholesale price of $595,000 per year. Ionis' Tryngolza revenue was $57.3 million in the nine months ended Sept. 30, the first product Ionis has commercialized without a partner.
While FCS is a minor indication, Arrowhead and Ionis are also testing their drug in the more common form of severe hypertriglyceridemia (SHTG). Like FCS, SHTG is characterized by higher triglyceride levels, but the cause is a combination of genetic, medical, and lifestyle factors. An estimated 3 million people have this disease; approximately 1 million people have high-risk SHTG, which increases the risk of acute pancreatitis.
In SHTG, Ionis said Tryngolza could be priced around $20,000. Arrowhead is taking a broader approach to pricing. CEO Chris Anzalone said on a conference call on Tuesday that Redemlo is not just an FCS therapy, but can also treat pancreatitis regardless of its cause. He said the company would not ask different patients to pay different prices for the same drug. Redemplo's annual wholesale price in the FCS is $60,000 and will be the same for SHTG and any other potential future indications for the drug.
“Ultimately, there's a huge economic opportunity here in the SHTG community, so it's critical that we get the right price for it, and if that means we give up some short-term revenue from FCS, we view it as an investment in the future,” Anzalone said. “The real economic opportunity here, and our focus, at least on the economic side, is making sure the price is reasonable, and the initial population here from our perspective is the high-risk SHTG patients.”
Leerink Partners analyst Mani Foroohar said in a note to investors that Arrowhead's pricing of Redemplo was surprising. Foroohar said the labels for the two FCS drugs are essentially similar, with the main difference being dosing frequency. Arrowhead's drug had greater lipid inhibition, but comparisons across trials have always been challenging. Foroohar noted that the timing of this measure is month 10 for Arrowhead and month 6 for Ionis.
Foroohar said near-term adoption of these products will be driven by commercial execution as well as pricing and access. Based on Leerink's discussions with clinicians, both drugs are exciting. Doctors believe the safety profile is manageable, and the company believes the two drugs have different chances of lowering triglycerides. Leerink is following SHTG's data readings for Ionis and Tryngolza's pricing strategy.
Arrowhead describes Redemplo as having multi-billion dollar revenue potential across multiple indications. The company expects the drug to be available for FCS patients by the end of this year. As for global commercialization of the drug, Anzalone said Arrowhead is open to finding partners for the drug but is not dependent on one.
Photo by Arrowhead Pharmaceuticals
