Arrowhead Pharmaceuticals Lines Up SHASTA Readout as REDEMPLO Launch Gains Traction

Key Points

• SHASTA-3 and SHASTA-4 topline data for plozasiran in severe hypertriglyceridemia remain on track for third-quarter reporting, with Arrowhead saying it is cautiously optimistic but still waiting on final patient visits and event adjudication.
• The REDEMPLO launch for familial chylomicronemia syndrome is gaining traction, and management said early uptake is trending better than Ionis’ comparable launch, helped by a reduced $45,000 list price and positive payer feedback.
• Arrowhead also highlighted multiple upcoming pipeline catalysts across obesity, MASH, CNS, and lipid programs, including more data for ARO-INHBE, ARO-ALK7, ARO-MAPT, the APOC3-PCSK9 dimer program, and potential enrollment completion for zodasiran later this year.

Arrowhead Pharmaceuticals NASDAQ: ARWR executives outlined upcoming clinical catalysts, early commercial trends and pipeline priorities during a Jefferies fireside chat, with Chief Medical Officer James Hamilton emphasizing that the company remains focused exclusively on siRNA therapeutics through its TRiM, or Targeted RNAi Molecule, platform.

Hamilton said Arrowhead has advanced 20 clinical candidates into various stages of development. Partnered programs include olpasiran with Amgen, fazirsiran with Takeda, hepatitis B and MASH programs with GSK, a broad discovery collaboration with Sarepta and a recently announced discovery collaboration with Novartis. On the wholly owned side, Hamilton highlighted REDEMPLO, which was recently approved for familial chylomicronemia syndrome, as well as plozasiran in severe hypertriglyceridemia, zodasiran in homozygous familial hypercholesterolemia, obesity candidates ARO-ALK7 and ARO-INHBE, and ARO-MAPT for tau-related neurological diseases.

SHASTA Data Remain on Track for Third Quarter

Hamilton said the company remains on schedule to report topline data in the third quarter from SHASTA-3 and SHASTA-4, pivotal studies of plozasiran in severe hypertriglyceridemia. He said the final patients are expected to complete visits “over the next month or so,” but Arrowhead is not narrowing its guidance to a specific month because late acute pancreatitis events or serious adverse events could still require adjudication.

On the acute pancreatitis endpoint, Hamilton said Arrowhead remains “cautiously optimistic” while blinded to the data. He said the company has previously indicated that roughly nine or more acute pancreatitis events, with event rates similar to those seen in CORE and CORE2 studies, would provide around 80% power. He added that events have not appeared “wildly out of our range of expectations,” but said the outcome will not be known until the third-quarter readout.

Hamilton said Arrowhead does not plan changes to its statistical analysis plan and has long planned to pool acute pancreatitis data from SHASTA-3 and SHASTA-4. He also said baseline triglyceride values across the combined studies are about 860, compared with about 600 in the SHASTA-2 study, where the company saw approximately a 70% triglyceride reduction. He said a 10% decline in the placebo group “wouldn’t surprise” him, reflecting diet adherence and potential reversion to the mean.

Safety, Liver Fat and Competitive Context

Asked about Ionis’ olezarsen, Hamilton said he expects approval and said acute pancreatitis may be included in the label, though he said it is unclear where such information would appear. He described the CORE and CORE2 data as “really good and really convincing,” particularly on acute pancreatitis.

Hamilton also discussed safety differences between Arrowhead’s siRNA approach and antisense oligonucleotide, or ASO, therapies. He said Arrowhead is not seeing hypersensitivity reactions or thrombocytopenia, which he characterized as more consistent with ASO class effects. On liver fat, Hamilton said Arrowhead did not observe an increase at the 25-milligram dose in SHASTA-2, which he described as the go-to-market dose, though a 2% absolute increase from baseline was seen at a 50-milligram dose the company is no longer using. He said Arrowhead should provide an update on liver fat when it reports severe hypertriglyceridemia data.

REDEMPLO Launch and Pricing

Daniel Apel, Arrowhead’s chief financial officer, said the REDEMPLO launch in familial chylomicronemia syndrome is trending better than Ionis’ launch at a similar time point when normalized for price and viewed on a unit basis, though he cautioned against overemphasizing early numbers in an ultra-rare indication. He said there was some pent-up demand from expanded access program switches and some patients switching from TRYNGOLZA, but most demand has been new to class.

Apel said Arrowhead expects continued largely linear growth, primarily from patients naive to the APOC3 class, with some contribution from switchers. He cited REDEMPLO’s three-month dosing schedule, potency and lack of warnings, precautions or contraindications as factors the company believes will support physician choice.

On pricing, Apel said payer feedback has been positive after Arrowhead reduced REDEMPLO’s wholesale acquisition cost to $45,000 from $60,000. He said the move maintained a premium position while keeping the therapy within a range that payers view as cost comparable, and said payer discussions are proceeding well and aligned with the approved label.

Obesity, MASH and CNS Programs

Hamilton said recent EASL data for ARO-INHBE showed about a 40% reduction in liver fat from baseline in patients with hepatic steatosis, supporting a potential monotherapy pathway in MASH. He said Arrowhead is also evaluating ARO-INHBE with GLP-1 therapy, especially in diabetics, where it has seen additional weight loss versus GLP-1 alone.

Hamilton said ARO-ALK7 and ARO-INHBE studies are fully enrolled with about 240 total patients across monotherapy and tirzepatide combination cohorts. Additional ARO-INHBE cohorts include higher-dose monotherapy in Type 2 diabetics and combinations with 5 mg and 15 mg tirzepatide. He said Arrowhead plans more ARO-ALK7 data in the second half, focusing on body composition, weight loss, visceral fat and lean mass.

For ARO-MAPT, Hamilton said later-year data will focus on safety and tau knockdown in healthy volunteers, with patient data likely next year. He said Arrowhead would like to see total tau knockdown in cerebrospinal fluid comparable to the 50% to 60% reported by Ionis in Alzheimer’s patients, and said successful subcutaneous CNS knockdown would be important for the broader platform.

Additional Catalysts

Hamilton said Arrowhead plans to report third-quarter data from its APOC3-PCSK9 dimer program in patients with mixed hyperlipidemia. He said initial success would include total ApoB reductions of about 40% or better, with the company ultimately aiming to move toward outcomes testing after establishing long-term safety and dose.

Apel said Arrowhead is not planning to out-license additional programs or disclose new business development activity. He listed upcoming catalysts including SHASTA-3 and SHASTA-4 data, dimer data, ARO-MAPT cerebrospinal fluid data, additional obesity data and potential full enrollment of the zodasiran program later this year. No specific cash runway update was provided in the discussion.

About Arrowhead Pharmaceuticals NASDAQ: ARWR

Arrowhead Pharmaceuticals, Inc is a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of RNA interference (RNAi) therapeutics. Since its founding in 2008, Arrowhead has leveraged its proprietary delivery platform—known internally as the Advanced RNAi Compound (ARC) technology—to silence disease-causing genes in patients suffering from genetically defined diseases. The company's approach aims to offer durable, targeted treatments across a range of therapeutic areas.

The company's pipeline includes multiple candidates in various stages of development.

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