Small interfering RNA (siRNA) therapeutics are a nucleic-acid drug modality that reduces the production of a specific disease-driving protein by triggering the RNA interference (RNAi) pathway. Unlike small-molecule inhibitors that block a protein's function or antibodies that bind a protein in circulation, siRNA drugs act upstream at the mRNA level, cutting production of the target protein at the source. The class became commercially validated with the 2018 FDA approval of Onpattro (patisiran) and now spans multiple approved products.
On this site, siRNA appears primarily through its peptide-adjacent modality intersections. The lead peptide-adjacent siRNA franchises: Alnylam's Amvuttra (vutrisiran) for transthyretin (ATTR) amyloidosis; Alnylam's obesity pipeline including ALN-6222 (Phase 1, NCT07624071) and ALN-2232 (Phase 1 readout second half 2026); Novartis's Leqvio (inclisiran) for PCSK9-mediated LDL cholesterol reduction (twice-yearly subcutaneous injection); and Arrowhead Pharmaceuticals's plozasiran (Redemplo) for severe hypertriglyceridemia (Phase 3 SHASTA-3 and SHASTA-4 positive data July 23, 2026, 79-81% median triglyceride reductions).
The Alnylam-PeptiDream collaboration announced in 2021 has produced a December 2025 preclinical milestone demonstrating peptide-ligand-mediated targeted siRNA delivery to specific extrahepatic tissues, opening a peptide-siRNA conjugate platform that could extend the siRNA modality beyond the liver (the default extraction site for GalNAc-conjugated siRNAs). Stories here cover siRNA trial readouts, approvals, and the peptide-siRNA conjugate delivery platforms that increasingly bridge peptide chemistry and nucleic-acid pharmacology. See [[alnylam]], [[peptidream]], and [[peptide-conjugate]] for adjacent threads.
Silence Therapeutics (NASDAQ: SLN) announced the closing of its upsized $201.3 million underwritten public offering of American Depositary Shares. Terms: priced August 11 at $13.50 per ADS for 12,962,963 ADSs. The underwriters (Jefferies, Morgan Stanley, Cantor Fitzgerald, and William Blair as joint book-running managers) fully exercised their 30-day option to purchase an additional 1,944,444 ADSs, bringing the total offering to 14,907,407 ADSs and gross proceeds to approximately $201.3 million. The financing follows the August 10 Phase 2 SANRECO trial win in polycythemia vera with divesiran (first-in-class TMPRSS6-targeting siRNA that increases hepcidin production to restrict iron availability to bone marrow) achieving an 88% response rate versus 19% on placebo (P<0.0001, 69% placebo-adjusted response rate) in 48 phlebotomy-dependent patients over 36 weeks. Use of proceeds: advance divesiran into Phase 3 (planned initiation H1 2027 evaluating Q12W dosing versus placebo) plus broader pipeline progression including hepatic-target GalNAc-conjugated siRNA portfolio across TMPRSS6, complement component 3 (SLN-124/SLN-501), and other liver-targeted RNAi candidates. Divesiran has FDA Fast Track and Orphan Drug designations for polycythemia vera.
Silence Therapeutics (NASDAQ: SLN) closed its upsized $175 million underwritten public offering of American Depositary Shares (ADSs) following the August 10, 2026 Phase 2 SANRECO trial win in polycythemia vera. Trial anchor: divesiran achieved 88% response versus 19% on placebo (P<0.0001, 69% placebo-adjusted response rate) in 48 phlebotomy-dependent patients over 36 weeks. Offering mechanics: priced August 11 at $13.50 per ADS for 12,962,963 ADSs. The underwriters (Jefferies, Morgan Stanley, Cantor Fitzgerald, and William Blair as joint book-running managers) fully exercised their 30-day overallotment option for an additional 1,944,444 ADSs, bringing the total offering to 14,907,407 ADSs and gross proceeds to approximately $175 million. The financing provides the capital to advance divesiran into Phase 3 (planned initiation H1 2027) plus broader pipeline progression including the GalNAc-conjugated hepatic-target siRNA portfolio across TMPRSS6, complement component 3 (SLN-124/SLN-501), and other hepatic and extrahepatic targets. Divesiran has FDA Fast Track and Orphan Drug designations for polycythemia vera; the transferable-voucher secondary market and the recently completed Arrowhead $215 million Priority Review Voucher purchase provide comparable references for the broader siRNA regulatory-instrument landscape.
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.
Alnylam Pharmaceuticals (NASDAQ: ALNY) reports Q2 2026 earnings Thursday July 30, 2026 before market open with an 8:30 AM ET conference call. Wall Street consensus estimates: EPS of $2.05 (+540.6% year-over-year) and revenue of $1.32 billion (+70.4% year-over-year), reflecting the continued commercial ramp of Amvuttra (vutrisiran) across both hereditary transthyretin amyloid polyneuropathy (hATTR-PN) and hereditary transthyretin amyloid cardiomyopathy (hATTR-CM) after the Q1 2026 Amvuttra revenue of $889.9 million (+187% YoY). Analyst focus areas beyond the base-business ramp include: the ALN-6222 first-in-human Phase 1 obesity siRNA program (NCT07624071) that opened enrollment in July 2026 as a randomized double-blind placebo-controlled single-ascending-dose study of an undisclosed-target subcutaneous siRNA in adults with BMI 30-40 kg/m²; the ALN-2232 Phase 1 obesity program (Alnylam's second obesity-track siRNA) with Phase 1 readout expected in the second half of 2026; the Alnylam-PeptiDream peptide-siRNA conjugate extrahepatic delivery platform milestone announced December 2025; and the broader Alnylam 2030 strategy launch positioning beyond the Amvuttra franchise.
Alnylam Pharmaceuticals (NASDAQ: ALNY) reports Q2 2026 earnings Thursday July 30, 2026 before market open. Analyst focus areas include the new ALN-6222 investigational subcutaneous siRNA obesity Phase 1 trial (NCT07624071, first-in-human single-ascending-dose randomized double-blind placebo-controlled design enrolling approximately 88 adults with BMI 30 to less than 40 kg/m² and HbA1c below 6.5% at a single site in Mount Royal, Canada through December 2027; molecular target of ALN-6222 has not been publicly disclosed). Also under focus: the Phase 1 ALN-2232 program (Alnylam's second obesity-track siRNA, with a Phase 1 readout expected in the second half of 2026), the Alnylam-PeptiDream peptide-siRNA conjugate extrahepatic delivery platform milestone announced December 2025 (demonstrating peptide-ligand-mediated targeted siRNA delivery to specific extrahepatic tissues), and the broader Alnylam 2030 strategy launch positioning beyond the Amvuttra (vutrisiran) transthyretin amyloidosis franchise. Alnylam's obesity pipeline is programmed against inhibin subunit beta E (INHBE) in liver and activin receptor type 1C (ACVR1C) in adipose tissue, both nucleic-acid modality targets that are distinct from GLP-1 agonism.
Alnylam Pharmaceuticals (NASDAQ: ALNY) confirmed a first-in-human Phase 1 trial of ALN-6222, an investigational subcutaneous siRNA therapeutic in adults with obesity, in a July 22 filing update on ClinicalTrials.gov (NCT07624071). The randomized, double-blind, placebo-controlled, single ascending dose study will enroll approximately 88 participants with a BMI of 30 to less than 40 kg/m² and an HbA1c below 6.5% (excluding participants with diabetes). The primary endpoints are safety and pharmacodynamics; secondary endpoints include changes in body weight and metabolic markers. The molecular target of ALN-6222 has not been publicly disclosed. The trial is set to run through December 2027 at a single site in Mount Royal, Canada. ALN-6222 marks Alnylam's first clinical-stage entry into the obesity therapeutic area, joining a broader wave of nucleic-acid, peptide, and peptide-fusion modalities entering the space beyond the GLP-1 incumbents (Wegovy, Ozempic, Mounjaro, Zepbound) and the Alnylam-PeptiDream peptide-siRNA conjugate collaboration announced in 2021. Alnylam separately reports Q2 2026 earnings later this week and is expected to discuss the ALN-6222 program on the call.
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.