You’d think a drug that brought in more than $1 billion in quarterly sales would signal success. But when Alnylam Pharmaceuticals reported $1.01 billion in second-quarter Amvuttra sales — below published consensus estimates — and trimmed its full-year outlook for the broader transthyretin franchise in late July, its shares tumbled nearly 30%.
Amvuttra lowers production of a protein called transthyretin, which can misfold and form amyloid deposits in organs and tissues. Alnylam cut 2026 revenue guidance for Amvuttra and Onpattro, another player in its transthyretin franchise, by $200 million to the $4.2 billion to $4.5 billion range. The company attributed the revision mainly to normalizing second-line demand after an initial wave of patients came onto the treatment after Amvuttra’s 2025 expansion into ATTR cardiomyopathy, or ATTR-CM. That adjusted revenue revision fell 4% short of Wall Street expectations.
The FDA first approved Amvuttra in 2022 for polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults, then expanded its use in March 2025 to cardiomyopathy caused by wild-type or hereditary ATTR amyloidosis. The indications were steadily expanding; the modality seemed like a safe bet.
But investors may have also been responding to additional background factors. Amvuttra competes in ATTR-CM with stabilizers including Pfizer’s Vyndamax and BridgeBio’s Attruby. Wainua, an AstraZeneca-Ionis gene silencer approved for the polyneuropathy form of hereditary ATTR amyloidosis, had been a potential rival in cardiomyopathy before failing a phase 3 trial in July.
That failure initially appeared to remove a competitor, but the limited top-line results exposed another wrinkle: Wainua showed no treatment effect among patients already taking a stabilizer. Some investors read that subgroup result as potentially relevant to Amvuttra, although cross-trial comparisons are limited and full Wainua data had not yet been presented.
Alnylam remains confident. CEO Yvonne Greenstreet said the company would continue to “invest robustly in this franchise” as it works to establish Amvuttra as “a foundational therapy.” Even so, the episode illustrates how a blockbuster can disappoint when investors have priced in faster growth.
But Amvuttra wasn’t the only high-profile candidate to fall short of analyst expectations this year. Three other franchises face pressure — for different reasons.
AbbVie’s Imbruvica
AbbVie’s Imbruvica narrowly missed Q2 analyst expectations, generating $532 million in second-quarter global net revenue against a consensus estimate of roughly $533 million. Sales fell 29.4% year over year. The decline came as Imbruvica faced pressure from Medicare’s newly effective negotiated price, set 38% below its 2023 list price, and growing competition from newer BTK inhibitors.
The lower negotiated price bargained under the Inflation Reduction Act, which reduced the list price from $14,934 in 2023 to $9,319 in 2026, isn’t the only setback the drug has faced in recent years. After its 2013 approval, it quickly became a mainstay oncology therapy, primarily in blood cancers, such as chronic lymphocytic leukemia. But second-and-third generation BTK inhibitors, such as AstraZeneca’s Calquence, BeOne Medicines’ Brukinsa, and Eli Lilly’s Jaypirca, which produce fewer side effects, have eroded its market share.
Longer term, Imbruvica could face generic competition, although AbbVie does not expect U.S. generic entry before March 2032.
Merck’s vaccines
Merck’s chickenpox vaccine Varivax, its MMR-II vaccine for measles, mumps and rubella, and the MMRV combination vaccine ProQuad generated $592 million in Q2. That was about 2.6% below the $608 million analysts expected, according to Reuters, and 2.8% below the year-earlier period.
Merck attributed the year-over-year decline primarily to lower U.S. demand, partly offset by higher U.S. net pricing, increased European demand and favorable private-sector purchasing patterns for MMR-II in the U.S.
Federal vaccine policy has become more volatile under HHS 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 later stayed in a preliminary injunction, which the administration appealed. Merck did not attribute this quarter’s decline specifically to those policy changes.
Roche’s Vabysmo
Roche’s Vabysmo generated about $1.27 billion in Q2, 7.1% below analyst consensus and down 1% year over year. CEO Teresa Graham attributed the shortfall partly to slower retinal-market growth, which she said was settling into a “new normal” of 2% to 3%.
Vabysmo grew rapidly after its 2022 approval, but momentum slowed in the second half of 2025 as closures of some copay-assistance foundations contributed to a contraction in the U.S. branded retinal-drug market. That slowdown was not an across-the-board sales decline: Roche reported first-half 2026 Vabysmo sales up 8% at constant exchange rates.
Vabysmo also competes with Regeneron’s branded Eylea and Eylea HD.
Graham nevertheless called consensus peak-sales expectations of about $7.4 billion (6 billion Swiss francs) “very reasonable” and said Roche was “confident that we’re on track to achieve this number.” More than 60% of U.S. Vabysmo patient starts were treatment-naïve as of January, and the drug is being studied in phase 3 for a potential fourth indication, myopic choroidal neovascularization
