Merck Targets $70B Pipeline Opportunity as Keytruda Loss of Exclusivity Nears in 2028
核心洞察
Merck (搜索) is building its next growth phase around a phase III pipeline that has nearly tripled since 2021 and a target of 20 new drug launches by 2030.
The company projects more than $70 billion in non-risk-adjusted commercial opportunity from its current pipeline by the mid-2030s, more than double Keytruda's $35 billion peak consensus estimate.
Merck (搜索) and Moderna reported the first positive phase 3 result for a personalized mRNA cancer vaccine, though detailed efficacy and overall survival data remain pending.
Merck (搜索) is positioning a rapidly expanding pipeline and a portfolio of newly launched medicines to absorb the 2028 loss of exclusivity (LOE) for Keytruda, its largest revenue driver. The company expects more than $70 billion of potential non-risk-adjusted commercial opportunity from its current pipeline by the mid-2030s — an estimate more than double the peak consensus sales estimate of $35 billion for Keytruda in 2028.
Keytruda generated $16.40 billion in first-half 2026 sales, up nearly 4.2% year over year, and is expected to remain strong until patent exclusivity expires in 2028. Once biosimilars enter around 2028–2029, however, sales are likely to decline sharply. Merck (搜索)'s phase III pipeline has almost tripled since 2021, supported by internal progress and acquisitions, and the company expects to launch 20 new drugs by 2030.
Newer Products Take On Growth Duties
Several recently launched products are already emerging as key growth drivers. Pulmonary arterial hypertension drug Winrevair and 21-valent pneumococcal conjugate vaccine Capvaxive generated $1.1 billion and $325 million, respectively, in first-half 2026 sales, while cancer drug Welireg sales surged 57% year over year to $470 million.
Merck (搜索) has also secured approvals for RSV antibody Enflonsia (搜索) (clesrovimab), HIV (搜索) treatment Idvynso (搜索) — a once-daily, single-tablet, two-drug regimen of doravirine and islatravir — and Lipfendra (搜索) (enlicitide), an oral PCSK9 inhibitor for lowering LDL cholesterol in adults with hypercholesterolemia (搜索).
Late-stage candidates include sacituzumab tirumotecan (sac-TMT), an anti-TROP2 (搜索) antibody-drug conjugate for multiple tumor types; MK-8591D/islatravir plus lenacapavir, a once-weekly oral HIV (搜索) treatment; and alimatravir (搜索), a monthly oral HIV PrEP candidate.
ADC Combinations and Women's Cancers
Merck (搜索) is testing whether pairing antibody-drug conjugates with Keytruda can improve treatment for breast and gynecologic cancers while preparing for the Keytruda patent cliff. The strategy places patient tolerability alongside efficacy, with the company hoping the combinations improve outcomes without adding a significant toxicity burden, according to Dr. Shweta Jain, vice president of global clinical development at Merck.
Sacituzumab tirumotecan recently improved overall and progression-free survival in a phase 3 trial in previously treated endometrial cancer (搜索). Merck (搜索) is testing ADCs alone and alongside Keytruda across several women's cancers, with a broader goal of replacing chemotherapy in some regimens. Company representatives said Merck intends to study sac-TMT broadly across PD-L1 (搜索)-related indications and sees potential combination opportunities with a PD-1/VEGF (搜索) approach, including with Welireg.
Personalized Cancer Vaccines Face a Scale Challenge
Merck (搜索) and Moderna last month reported the first positive phase 3 result for a personalized mRNA cancer vaccine, a milestone that also underscored how much work remains. Detailed efficacy data and overall survival results are still pending.
The commercial challenge is built into the product: each vaccine requires sequencing a patient's tumor, selecting targets and manufacturing an individualized batch — a scale-out model that must run thousands of production cycles in parallel rather than producing one standardized drug at high volume.
On individualized neoantigen therapy (INT), Merck (搜索) has focused development where Keytruda has already shown activity in earlier-stage disease and across tumors with varying tumor mutation burdens. In melanoma (搜索), phase II data suggested that adding INT to Keytruda "almost double[s]" the number of patients remaining cancer-free compared with Keytruda alone, though the company emphasized that investors will look to the phase III presentation to assess how closely results align with the earlier study. Renal cell carcinoma (搜索) data could serve as another reference point for assessing INT across other immune-sensitive tumors, including non-small cell lung cancer (搜索) and head and neck cancer (搜索).
Beyond Oncology: Ophthalmology, Immunology and Cardiometabolic Bets
Merck (搜索)'s ophthalmology strategy includes MK-3000, a Wnt agonist, and MK-8748, an anti-VEGF (搜索) Tie2 agonist. The company is pursuing each independently but sees potential for the pair to offer ophthalmologists both a non-VEGF treatment option and a potential best-in-class anti-VEGF therapy. An estimated 30% to 40% of patients either do not respond or stop responding to anti-VEGF therapies; Merck hopes MK-3000 can establish a new treatment mechanism, while MK-8748 is being developed with the ambition of showing faster retinal drying than existing anti-VEGF options.
In immunology, Merck (搜索) aims to position its TL1A (搜索) program as an important treatment "node" alongside TNF, IL-23 and IL-17 approaches, targeting gastrointestinal, dermatology and rheumatology indications with a biologic that is highly effective and has a strong safety profile.
For Lipfendra (搜索), Merck (搜索) sees substantial potential, noting that 30 million U.S. patients on statins are not at their LDL target, with roughly half in secondary prevention and half in primary prevention. The company initially expects more use among patients with established ASCVD and described early prescription trends as encouraging, continuing to view the drug as a multibillion-dollar peak-revenue opportunity with uptake expected ahead of the SEAFOOT study.
LOE Framed as a "Hill," Not a Cliff
Merck (搜索) does not expect a revenue cliff during the Keytruda LOE period. Instead, management expects "more of a hill with a quick return to strong growth" on a risk-adjusted basis, while continuing to aspire to grow through the LOE period on a non-risk-adjusted basis. The company said it is focused on sustainable long-term growth rather than a specific revenue profile in a single year, and management has described the LOE period as a "shallow dip with a fast return back to growth."
Looking to 2027, Merck (搜索) expects modest top-line growth supported by recently launched products, partly offset by generic competition affecting Bridion, Januvia and Adempas, which loses exclusivity at the end of the year. Keytruda growth is slowing as the product matures, and policy changes in Germany are expected to create pricing pressure next year. Merck Animal Health is expected to continue growing strongly. The company also expects gross-margin improvement from the expiration of a Keytruda royalty, with expense growth in the mid- to high-single-digit range excluding business-development upfront payments and funding received for sac-TMT, and somewhat higher interest expense following debt issuance for business development.
Competitive and Business Development Landscape
Keytruda faces competition from other PD-L1 (搜索) inhibitors, including Bristol Myers Squibb (搜索)'s Opdivo, Roche's Tecentriq and AstraZeneca's Imfinzi. Bristol Myers recorded $4.63 billion in Opdivo sales in the first half of 2026, down 3.9% year over year. Roche recorded CHF 1.70 billion in Tecentriq sales, up 6%, while Imfinzi generated $3.55 billion, up 29%, driven by demand growth across established indications and new launches.
Merck (搜索) has stepped up acquisitions ahead of the 2028 patent expiry, with deals for Verona Pharma, Cidara Therapeutics and Terns Pharmaceuticals expanding its pipeline across COPD (搜索), influenza (搜索) and oncology, respectively. Management said the company will continue seeking externally sourced science that addresses unmet medical needs, identifying transactions in the $1 billion to $15 billion range as a continuing sweet spot, with interest in oncology, cardiometabolic disease and immunology.
Prediction Markets Add a Compliance Dimension
Beyond pipeline strategy, prediction markets now allow people to wager directly on clinical trial outcomes and FDA decisions, placing a visible price on information that can move a drugmaker's value. According to Mark Scallon, a principal at Baker Tilly who advises life sciences companies on compliance programs, auditing and risk, the industry should address the consequences immediately. Awareness is the critical first step: companies should map who can access tradable milestones, update training and confidentiality policies, and scrutinize controls at CROs, labs, manufacturers and other third-party partners. Scallon noted that prediction markets do not necessarily create a wholly new compliance problem, but they make confidential information more directly monetizable and widen the circle of people companies must consider when protecting sensitive milestones.