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.
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.