Amvuttra (vutrisiran) is Alnylam Pharmaceuticals's GalNAc-conjugated small interfering RNA (siRNA) therapeutic that reduces hepatic production of transthyretin (TTR) protein. It is FDA-approved for hereditary transthyretin amyloid polyneuropathy (hATTR-PN, approved June 2022) and hereditary and wild-type transthyretin amyloid cardiomyopathy (ATTR-CM, expanded indication approved March 2025). Administration is a single subcutaneous injection every 3 months, a substantially reduced burden compared with the every-3-week IV infusion required for the earlier Onpattro (patisiran).
The ATTR-CM launch has driven Alnylam's commercial franchise into the top-tier RNAi therapeutics category. Amvuttra Q1 2026 revenue reached $889.9 million (+187% year-over-year), and Q2 2026 revenue crossed $1 billion for the first time at $1.012 billion (approximately a $4 billion annualized run rate about 15 months after the ATTR-CM launch). Alnylam revised full-year 2026 TTR product sales guidance down to $4.2-4.5 billion on the Q2 earnings call to reflect normalized second-line volume after initial pent-up demand.
Amvuttra competes with Pfizer's Vyndaqel/Vyndamax (tafamidis, small-molecule TTR stabilizer, approved 2019) and BridgeBio's Attruby (acoramidis, next-generation TTR stabilizer, approved November 2024) in the ATTR-CM segment. The siRNA mechanism (reducing TTR production at the mRNA level) is mechanistically distinct from the stabilizer mechanism (binding circulating TTR to prevent misfolding), and head-to-head clinical evidence continues to shape prescribing patterns.
Stories here cover Amvuttra commercial performance, competitive positioning, real-world outcomes, and Alnylam pipeline advances beyond the TTR franchise. See [[alnylam]], [[sirna]], and [[hattr-cm]] for adjacent threads.
Alnylam Pharmaceuticals (NASDAQ: ALNY) presented Monday September 14, 2026 at 10:00 a.m. ET at the Morgan Stanley 24th Annual Global Healthcare Conference in New York with CEO Yvonne Greenstreet and John Kennedy (SVP Global Commercialization / TTR Franchise Lead), disclosing a modest trim to full-year TTR franchise revenue guidance as early AMVUTTRA (vutrisiran, subcutaneous RNAi TTR silencer approved March 2025 for adults with ATTR amyloidosis with cardiomyopathy) launch demand normalized. Management emphasized the underlying market remains large and underdiagnosed, physician adoption is strong, and pipeline funding from AMVUTTRA commercial success is not at risk. AMVUTTRA competes in ATTR-CM against Pfizer's Vyndaqel/Vyndamax (tafamidis, oral small-molecule stabilizer) plus the recently launched BridgeBio Attruby (acoramidis, oral) — the launch mix has shifted as switch-from-tafamidis patients and treatment-naive patients balance out. HELIOS-B Phase 3 data anchored the approval with a 33% reduction in the composite of all-cause mortality plus recurrent cardiovascular events at 36 months. The trim adds nuance to the Alnylam commercial story that had run largely positive through Q2 2026 earnings; investors focused on the deeper pipeline (nucresiran next-generation TTR silencer plus the broader RNAi platform) rather than the near-term guidance move.
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).
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.