Alnylam Pharmaceuticals (NASDAQ: ALNY), headquartered in Cambridge, Massachusetts, is the pioneering RNA interference (RNAi) therapeutics company that turned an academic biology finding into a commercial-stage drug class. The commercial franchise is anchored in cardiovascular and rare-disease indications, with Amvuttra (vutrisiran) as the lead product for transthyretin (ATTR) amyloidosis in both hereditary polyneuropathy and cardiomyopathy indications.
On this site, Alnylam appears primarily through its obesity pipeline entry and its peptide-adjacent modality intersections. The ALN-6222 first-in-human Phase 1 obesity trial (NCT07624071) 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 and HbA1c below 6.5% at a single site in Mount Royal, Canada, targeting completion in December 2027. A second obesity siRNA, ALN-2232, is expected to produce Phase 1 readout in the second half of 2026. The Alnylam obesity pipeline targets include inhibin subunit beta E (INHBE) in liver and activin receptor type 1C (ACVR1C) in adipose tissue.
The Alnylam-PeptiDream collaboration first announced in 2021 produced a December 2025 preclinical milestone demonstrating peptide-ligand-mediated targeted siRNA delivery to specific extrahepatic tissues, laying groundwork for a peptide-siRNA conjugate platform beyond the liver. Stories here cover Alnylam trial readouts, franchise commercial performance, and pipeline milestones. See [[sirna]], [[amvuttra]], and [[obesity]] for adjacent threads.
Alnylam Pharmaceuticals (NASDAQ: ALNY) presented Saturday August 29 and Sunday August 30, 2026 late-breaking prespecified subgroup analyses from the Phase 3 HELIOS-B trial of vutrisiran (AMVUTTRA, an RNAi therapeutic targeting transthyretin for transthyretin amyloidosis with cardiomyopathy, ATTR-CM) at ESC Congress 2026 Munich. Vutrisiran demonstrated consistent clinical benefit across all-cause mortality and recurrent cardiovascular events in patients with or without background tafamidis (the transthyretin tetramer stabilizer marketed as Vyndaqel/Vyndamax by Pfizer). The HELIOS-B trial had documented 28.2% reduction in all-cause mortality and 32.8% reduction in cardiovascular events with vutrisiran plus stabilizer. Additional analyses examined healthy aging, functional capacity, safety, and outcomes by sex. Alnylam also presented Amylo'ExTTRa, a large real-world analysis from the French National Health Data System characterizing the multisystem burden of ATTR-CM beyond cardiac manifestations. Vutrisiran anchors Alnylam's ATTR franchise alongside inclisiran (Leqvio, licensed to Novartis for hypercholesterolemia) and zilebesiran (Phase 3 ZENITH trial in hypertension).
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.
The peptide-and-obesity Q2 2026 earnings week (Merck August 4, Pfizer August 4, Amgen August 4, Eli Lilly August 5, Novo Nordisk H1 August 4-5) delivered mixed signals across the pharma sector. Merck (NYSE: MRK) posted $16.61 billion Q2 revenue (+5% YoY, beat consensus by $250M), raised FY revenue guidance to $66.3-67.3 billion but cut adjusted EPS guidance to $2.66-2.76 due to a $5.7 billion Terns Pharmaceuticals acquisition charge; Keytruda reached $8.37 billion (+5%) and LIPFENDRA (enlicitide) launched at $315/month with $5 billion peak sales potential by 2034. Pfizer (NYSE: PFE) reported $15 billion revenue and $0.77 adjusted diluted EPS, raised FY revenue guidance midpoint to $60.5-62.5 billion, and CEO Bourla said the obesity program (danuglipron plus Metsera pipeline) is advancing with substantial momentum. Amgen (NASDAQ: AMGN) reported $10.05 billion Q2 revenue (+10% YoY), raised FY guidance to $38.2-39.4 billion, discontinued AMG 513 early-stage obesity candidate leaving MariTide as sole obesity focus. Eli Lilly (NYSE: LLY) delivered $23 billion Q2 revenue (+48% YoY blowout), raised FY guidance to $85-87 billion, Mounjaro reached $9.9 billion (+91%), Zepbound $4.9 billion US (+44%), and Foundayo generated $98 million in first fully operational commercial quarter. Novo Nordisk H1 reached 78.49 billion DKK ($12.09 billion, +3% CER) with Wegovy pill at 5 million+ prescriptions and raised guidance; NVO shares fell 5% on margin concerns. Alnylam (NASDAQ: ALNY) extended a 30% selloff (approximately $12 billion market cap lost) since the July 30 Q2 report on the Amvuttra TTR guidance cut plus eplontersen setback.
Alnylam Pharmaceuticals (NASDAQ: ALNY) shares extended a roughly 30% selloff since the Thursday July 30, 2026 Q2 2026 earnings report, losing approximately $12 billion in market capitalization over the intervening days. The selloff reflects two consecutive negative signals for the RNAi therapeutics leader: the July 30 Amvuttra (vutrisiran, the TTR-directed siRNA that crossed $1 billion in quarterly revenue for the first time at $1.012 billion) full-year 2026 TTR product sales guidance cut to $4.2-4.5 billion (down from prior higher expectations) to reflect normalized second-line volume after the initial pent-up demand from patients waiting for a new therapy, combined with the July AstraZeneca-Ionis eplontersen (Wainua, antisense oligonucleotide) Phase 3 CARDIO-TTRansform study setback that complicates the broader ATTR-CM competitive landscape. The Amvuttra franchise has been positioned as the primary siRNA alternative to Pfizer's Vyndaqel/Vyndamax (tafamidis, small-molecule TTR stabilizer) and BridgeBio's Attruby (acoramidis, next-generation TTR stabilizer). Alnylam presents full eplontersen study data at a late-August medical meeting; analysts flagged the timing as a continued overhang until the presentation clarifies the ATTR-CM segment dynamics. Analyst commentary described the combination as a 'one-two punch' for the company.
Alnylam Pharmaceuticals (NASDAQ: ALNY) reported Q2 2026 earnings Thursday July 30, 2026 before market open. Amvuttra (vutrisiran) quarterly revenue crossed $1 billion for the first time at $1.012 billion (approximately a $4 billion annualized run rate approximately 15 months after the ATTR-CM launch). Total Q2 revenue reached $1.29 billion (+67% year-over-year) but fell short of the $1.31 billion analyst consensus. Net product revenues were $1.17 billion (+74% YoY) versus the $1.22 billion estimate. GAAP diluted EPS was $1.21 versus the $1.49 estimate. Full-year 2026 TTR product sales guidance was revised down to $4.2-4.5 billion to reflect normalized second-line volume after the initial pent-up demand from patients waiting for a new therapy. Pipeline updates: Alnylam expects to announce clinical data from Phase 1 and Phase 2 trials of ALN-6400 in healthy volunteers and patients with hereditary hemorrhagic telangiectasia (HHT) in second-half 2026, plus results from the Phase 1 trial of ALN-2232 (Alnylam's second obesity-track siRNA) in the same second-half window. The ALN-6222 obesity siRNA Phase 1 trial (NCT07624071) opened enrollment in July 2026 with a first-in-human single-ascending-dose design in adults with BMI 30-40 kg/m² at a single site in Mount Royal, Canada through December 2027.
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.
On June 4, 2026, Alnylam Pharmaceuticals announced a partnership worth up to $2 billion with Inceptive, the AI biotech focused on programmable RNA and peptide medicines, to apply machine learning to peptide discovery. The deal is the second major back-loaded peptide-AI collaboration to land in the same week, following Regeneron's expanded Parabilis tie-up tied to Phase 3 LAG-3 setbacks.