Four Pharma Franchises Stumble Despite Blockbuster Status
A drug generating more than $1bn in quarterly sales might ordinarily be cause for celebration. But when Alnylam Pharmaceuticals (ALNY) reported $1.01bn in second-quarter Amvuttra revenues — fractionally below published consensus estimates — and trimmed its full-year outlook for the broader transthyretin franchise, its shares tumbled nearly 30%.
Amvuttra works by lowering production of transthyretin, a protein that can misfold and form amyloid deposits in organs and tissues. Alnylam cut its 2026 revenue guidance for Amvuttra and Onpattro, a second drug in its transthyretin franchise, by $200mn to a range of $4.2bn to $4.5bn. The company attributed the revision primarily to normalizing second-line demand following an initial wave of patients who began treatment after Amvuttra's 2025 expansion into ATTR cardiomyopathy. The revised guidance came in roughly 4% below Wall Street expectations.
The FDA first approved Amvuttra in 2022 for polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults, before expanding its use in March 2025 to cardiomyopathy caused by wild-type or hereditary ATTR amyloidosis. With indications steadily broadening, the drug had appeared to be a reliable growth vehicle.
Investors may, however, have been responding to additional pressures in the background. Amvuttra competes in ATTR cardiomyopathy with stabilizers including Pfizer's (PFE) Vyndamax and BridgeBio's (BBIO) Attruby. Wainua, a gene silencer developed by AstraZeneca (AZN) and Ionis Pharmaceuticals (IONS) approved for the polyneuropathy form of hereditary ATTR amyloidosis, had been considered a potential rival in cardiomyopathy before failing a Phase 3 trial in July.
That failure initially appeared to clear a competitor from the field, but limited top-line results exposed a further complication: Wainua showed no treatment effect among patients already taking a stabilizer. Some investors interpreted that subgroup finding as potentially relevant to Amvuttra, though cross-trial comparisons carry significant limitations and full Wainua data had not yet been presented.
Amvuttra was not alone. Three other major franchises missed analyst expectations in the second quarter, each for distinct reasons.
AbbVie's Imbruvica
AbbVie's (ABBV) Imbruvica narrowly missed second-quarter expectations, generating $532mn in global net revenues against a consensus estimate of approximately $533mn — a decline of 29.4% year over year. The drug faced a double headwind: a newly effective Medicare negotiated price, set 38% below its 2023 list price under the Inflation Reduction Act, and intensifying competition from newer BTK inhibitors.
The negotiated price reduction — from $14,934 per course in 2023 to $9,319 in 2026 — compounds pressures that have been building for several years. After its 2013 approval, Imbruvica quickly became a mainstay in blood cancer treatment, particularly chronic lymphocytic leukemia. But second- and third-generation BTK inhibitors, including AstraZeneca's (AZN) Calquence, BeOne Medicines' (ONC) Brukinsa and Eli Lilly's (LLY) Jaypirca, which produce fewer side effects, have steadily eroded its market share. AbbVie does not expect US generic competition before March 2032.
Merck's vaccine portfolio
Merck's (MRK) childhood vaccine franchise — comprising chickenpox vaccine Varivax, the MMR-II measles, mumps and rubella vaccine, and the combination vaccine ProQuad — generated $592mn in the second quarter, roughly 2.6% below the $608mn analysts had forecast and 2.8% below the year-earlier period.
Merck attributed the year-over-year decline primarily to lower US demand, partly offset by higher domestic net pricing, increased European demand and favorable private-sector purchasing patterns for MMR-II in the US. The company stopped short of linking the quarterly shortfall to the more volatile federal vaccine policy environment that has emerged under Health and Human Services Secretary Robert F. Kennedy Jr., who dismissed all 17 members of the CDC's Advisory Committee on Immunization Practices last year. A January schedule that moved six vaccines out of the universally recommended category was subsequently stayed by a preliminary injunction, which the administration has appealed.
Roche's Vabysmo
Roche's (RHHBY) Vabysmo generated approximately $1.27bn in the second quarter, 7.1% below analyst consensus and down 1% year over year. Chief executive Teresa Graham attributed the shortfall partly to slower growth in the retinal market, which she said was settling into a new normal of 2% to 3% annual expansion.
Vabysmo grew rapidly following its 2022 approval, but momentum slowed in the second half of 2025 as closures of certain copay-assistance foundations contributed to a contraction in the US branded retinal-drug market. The picture was not uniformly negative: Roche reported first-half 2026 Vabysmo sales up 8% at constant exchange rates. The drug competes with Regeneron's (REGN) branded Eylea and Eylea HD.
Graham described consensus peak-sales expectations of approximately $7.4bn as very reasonable and said Roche remained confident of achieving that figure. More than 60% of US Vabysmo patient starts were treatment-naïve as of January, and the drug is under Phase 3 investigation for a potential fourth indication in myopic choroidal neovascularization.