Arrowhead Pharmaceuticals (NASDAQ: ARWR), headquartered in Pasadena, California, is a clinical- and commercial-stage RNAi therapeutics company with a proprietary Targeted RNAi Molecule (TRiM) platform for delivering siRNA to hepatic and extrahepatic tissues. The lead commercial asset is Redemplo (plozasiran), an ApoC-III-targeting siRNA administered as a 25 mg subcutaneous injection every three months.
Redemplo received FDA approval in November 2025 for familial chylomicronemia syndrome. The July 23, 2026 Phase 3 SHASTA-3 and SHASTA-4 readouts documented 79% and 81% median triglyceride reductions at Month 12 versus approximately 27% for placebo in severe hypertriglyceridemia, plus statistically significant reductions in acute pancreatitis events. Arrowhead plans to file a supplemental new drug application (sNDA) before end of 2026 for the sHTG indication, supported by a $215 million Priority Review Voucher (PRV) acquired in fiscal Q2 2026 to compress the FDA review from 10 to 6 months (projected 3x return on the PRV investment).
Beyond plozasiran, Arrowhead's pipeline includes ARO-INHBE (obesity, Phase 1/2a in combination with tirzepatide showed -9.4% weight loss at Week 16 versus -4.8% tirzepatide alone), ARO-ALK7 (obesity), and multiple hepatic-target siRNAs for cardiovascular and rare-disease indications. Q3 fiscal 2026 Redemplo prescription volume approximately doubled versus fiscal Q2 with continued momentum into the current quarter. Stories here cover Arrowhead trial readouts, commercial launch trajectory, and pipeline advances. See [[plozasiran]], [[redemplo]], and [[sirna]] for adjacent threads.
Silence Therapeutics (NASDAQ: SLN) announced positive topline results from the Phase 2 SANRECO trial of divesiran, a first-in-class TMPRSS6-targeting siRNA product candidate developed from the company's proprietary mRNAi GOLD platform. The trial enrolled 48 phlebotomy-dependent adults with polycythemia vera (PV) and evaluated divesiran 6 mg/kg administered subcutaneously every 6 weeks (Q6W) or every 12 weeks (Q12W) versus placebo over a 36-week randomized double-blind period. Results: 88% of divesiran-treated patients achieved a response versus 19% on placebo (P<0.0001), corresponding to a 69% placebo-adjusted response rate. How divesiran works: it silences TMPRSS6 (transmembrane serine protease 6) expressed almost exclusively in the liver; TMPRSS6 is a negative regulator of hepcidin, the body's master regulator of iron metabolism. By silencing TMPRSS6, divesiran increases hepcidin production and release by liver hepatocytes, which restricts iron availability to bone marrow and reduces the excessive red blood cell production that drives PV symptoms. Divesiran has FDA Fast Track and Orphan Drug designations for PV. Silence Therapeutics anticipates initiating a Phase 3 trial evaluating divesiran Q12W versus placebo in the first half of 2027. Shares rose sharply on the news, touching a 52-week high. The read-through extends the broader siRNA cardiometabolic and rare-disease franchise landscape that also includes Alnylam's Amvuttra and Arrowhead's Redemplo (plozasiran) in adjacent hepatic-target siRNA categories.
Arrowhead Pharmaceuticals (NASDAQ: ARWR) disclosed the full terms of its Priority Review Voucher (PRV) acquisition first mentioned on the August 4, 2026 fiscal Q2 2026 conference call. Terms: $215 million paid to an undisclosed seller under an asset purchase agreement expected to close in fiscal Q4 2026. Applied to: the plozasiran (Redemplo) supplemental new drug application (sNDA) for severe hypertriglyceridemia (sHTG), planned for submission before end of 2026 following the July 23, 2026 Phase 3 SHASTA-3 and SHASTA-4 positive readouts (79% SHASTA-3 and 81% SHASTA-4 median triglyceride reductions at Month 12 versus approximately 27% for placebo, plus statistically significant reductions in acute pancreatitis events). Return projection: Arrowhead management projects a 3x return on the $215 million PRV investment by shifting the plozasiran sHTG commercial uptake curve forward by approximately four months (the PRV compresses FDA new drug application review from the standard 10-month timeline to a 6-month priority review timeline). PRVs are transferable FDA-issued regulatory instruments awarded to sponsors that develop drugs for rare pediatric diseases, tropical diseases, or specific medical countermeasures; recent secondary-market transactions have priced PRVs in the $100-250 million range depending on demand and pipeline urgency. Redemplo (plozasiran) was FDA-approved November 2025 for familial chylomicronemia syndrome; the sHTG indication would substantially expand the addressable patient population.
Arrowhead Pharmaceuticals (NASDAQ: ARWR) confirmed on the Fiscal Q2 2026 conference call Tuesday August 4, 2026 that the company has acquired a Priority Review Voucher (PRV), a transferable FDA-issued voucher that provides the option to shorten a future FDA new drug application review from the standard 10-month timeline to a 6-month timeline. PRVs are issued to sponsors that develop drugs for rare pediatric diseases, tropical diseases, or specific medical countermeasures under FDA statutory authority; they are transferable and can be sold on the secondary market where recent transactions have priced PRVs in the $100-200 million range. Arrowhead did not disclose the specific candidate to which the PRV will be applied but the timing (following the July 23, 2026 Phase 3 SHASTA-3 and SHASTA-4 positive readouts for plozasiran/Redemplo in severe hypertriglyceridemia) suggests the voucher may support the sNDA filing planned before end of 2026 for the severe hypertriglyceridemia indication. Separately, REDEMPLO (plozasiran) prescription volume has approximately doubled over fiscal Q3 following the November 2025 FDA approval for familial chylomicronemia syndrome, with continued momentum into the current quarter. Arrowhead management expressed continued satisfaction with the launch trajectory approximately 8.5 months after initial approval.
Arrowhead Pharmaceuticals (NASDAQ: ARWR) reported positive Phase 3 topline results Thursday July 23, 2026 from the SHASTA-3 and SHASTA-4 studies of plozasiran, an ApoC-III-targeting siRNA administered as a 25 mg subcutaneous injection once every three months, in adults with severe hypertriglyceridemia (sHTG). Both trials met their primary endpoint: median triglyceride reductions of 79% (SHASTA-3) and 81% (SHASTA-4) at Month 12 versus approximately 27% for placebo. All prespecified secondary endpoints were met, including a statistically significant reduction in the rate of acute pancreatitis events compared with placebo. Arrowhead shares rose approximately 19% on the readout. The company plans to file a supplemental New Drug Application (sNDA) with the US FDA before the end of 2026 for the sHTG indication (which extends the current Redemplo label from familial chylomicronemia syndrome), and Arrowhead intends to use the SHASTA-3, SHASTA-4, and MUIR-3 program data for marketing authorization filings across multiple global geographies. Plozasiran is a nucleic-acid therapeutic (siRNA), an adjacent-modality to peptides that operates through RNA interference at the ApoC-III gene expression level to lower circulating triglycerides.
Arrowhead Pharmaceuticals presented Phase 1/2a interim clinical data on ARO-INHBE at EASL 2026 today (Rinki Murphy, MBChB, PhD presenting). ARO-INHBE is an RNAi therapeutic targeting the Activin E/ALK7 pathway — a genetically validated regulator of adipose fat storage. The data: a single 400 mg dose produced 85.3% mean maximum Activin E reduction with persistent effect beyond 3 months; ≥200 mg doses reduced liver fat 44%. In combination with low-dose tirzepatide 5 mg in obese patients with type 2 diabetes, ARO-INHBE doubled weight loss and tripled reductions in visceral fat, total fat, and liver fat versus tirzepatide alone. Effect persists through Week 24 supporting potential twice-yearly dosing. Arrowhead is engaging with regulatory authorities on Phase 2 designs in MASH and obesity. The combination data is the strongest evidence to date that adding a non-GLP-1 mechanism to incretin therapy can meaningfully amplify body-composition outcomes — a contrast to the GLP-1-alone monotherapy story that has dominated obesity-pharmacology since 2021.