Merck Has 26 Months to Move Keytruda Patients to a Shot Protected Until 2043

Merck’s Keytruda strategy has one objective: move as many US patients as possible onto Keytruda Qlex, a one-minute injection patented until 2043, before biosimilars of the intravenous original can launch in December 2028. On Merck’s own target most patients will not have moved by then, a Medicare proposal threatens the price protection the shot was meant to carry, and a new class of drug is aimed at Keytruda’s largest market.

Half of Merck’s revenue runs on a clock that stops market by market

Keytruda and Keytruda Qlex brought in $8,366 million in the second quarter, up 4% at constant exchange rates, against total company sales of $16,607 million, according to Merck’s results. Growth came from earlier-stage use in triple-negative breast, cervical, head and neck and bladder cancer, and from metastatic urothelial cancer. Management told analysts that US growth will moderate in several established indications because Keytruda is close to reaching every eligible patient there.

The patent estate is layered. Merck’s 2025 annual report lists the US compound patent at 2028, with two further patents in the same family expiring in 2029. Chief executive Rob Davis told analysts in February that these cover a method of making, to May 2029, and a method of use, to November 2029, and said that whether exclusivity ends in 2028 or 2029 does not change Merck’s strategy.

The sequence matters more than any single date. The royalty saving arrives two years before the first loss of exclusivity, while the Medicare price lands within weeks of possible US biosimilar entry, a double hit in a single quarter. Outside the US the runway extends to 2031 and beyond: a biosimilar launched in Argentina in 2025, and Merck expects more launches in smaller markets this year with an immaterial impact on 2026 sales.

Qlex is the defence, and Merck’s own target leaves most US use exposed

Keytruda Qlex combines pembrolizumab with berahyaluronidase alfa, an enzyme from Alteogen, and is given in about one minute every three weeks or two minutes every six. Sales rose from $128 million in the first quarter to $463 million in the second, helped by a permanent billing code from 1 April. Chief financial officer Caroline Litchfield said after the quarter that Qlex had reached a double-digit share of the US business and was on a path to 30% to 40% adoption by the end of 2027.

Merck announced on 21 September that Japan had approved the product for all 22 Keytruda indications there, to be sold as Keyject. The EU approved it in November 2025 as Keytruda SC, but Merck’s filings say country launches depend on reimbursement and on the outcome of litigation with Halozyme. Alteogen, which said in August it would receive its first $25 million sales milestone, is due royalties until its patents expire in 2043.

Merck is also writing Qlex into every new label. The US perioperative bladder indication with Padcev covers Keytruda and Keytruda Qlex alike, and the CHMP opinion of 18 September includes Keytruda SC. Parity matters because conversion has to reach every setting: an indication available only intravenously would anchor patients to the form biosimilars will undercut.

Every point of conversion before December 2028 moves volume from the contested pool to the protected one, which makes Qlex share the most important number Merck reports between now and the cliff. It also tells biosimilar makers where to aim: the hospital systems still infusing intravenously in 2028.

CMS could turn Qlex into a shield against biosimilars alone

Merck’s annual report says it expects Keytruda to be selected for Medicare price negotiation in 2027, with a government-set price effective from 1 January 2029. In June, CMS proposed that subcutaneous versions be negotiated at the same time as their intravenous originals, describing the change as closing a loophole that extends protected life. The proposal names no products. Keytruda Qlex and Bristol Myers Squibb’s Opdivo Qvantig fit its description.

If the rule is finalised in that form, Qlex keeps protecting Merck from biosimilar substitution, because biosimilars reference the intravenous product, but it stops protecting the Medicare price. Davis told analysts that Merck priced Qlex to drive adoption from the intravenous form, so the pitch to providers rests on chair time and capacity rather than on a pricing gap.

Earlier-stage labels add volume before 2028 and no exclusivity after

The second lane moves Keytruda earlier, where patients are treated with curative intent around surgery. On 18 September the CHMP backed Keytruda plus Padcev before and after cystectomy for resectable muscle-invasive bladder cancer regardless of cisplatin eligibility, based on KEYNOTE-B15, which cut the risk of event-free survival events by 47% and of death by 35% against neoadjuvant chemotherapy, with pathologic complete response of 55.8% against 32.5%. The FDA approved the regimen in July, and a European Commission decision is expected this quarter.

Head and neck cancer follows the same pattern. China’s regulator has approved perioperative Keytruda for resectable locally advanced head and neck squamous cell carcinoma, joining US and EU approvals based on KEYNOTE-689, where the regimen cut the risk of event-free survival events by 30%.

These indications deepen use before December 2028, and none of them extends exclusivity. Their value to Merck after the cliff depends on how many of those patients are on Qlex when biosimilars arrive.

Third parties keep choosing pembrolizumab as the partner. Perspective Therapeutics will test its alpha-emitting radiopharmaceutical [212Pb]PSV359 with Keytruda in FAP-positive solid tumours, with Merck supplying drug at no cost under an agreement announced on 14 September. Inhibrx reported a confirmed response rate of 48.3% against 26.5% when its OX40 agonist was added to Keytruda in first-line head and neck cancer, from 63 evaluable patients in a randomised Phase 2, a sample too small to carry subgroup claims.

Each trial keeps pembrolizumab at the centre of new regimens. Whether those regimens end up given with branded Qlex or a biosimilar is a question Merck has to settle in the label and the contract, years before any of them is approved.

The biosimilar queue is pairing developers with established sellers

Four pembrolizumab programmes moved in 2026, and the structure of the deals says more than the filings themselves.

Qilu and Formycon have chosen partners with existing sales operations in their target markets, which is how a biosimilar reaches oncology formularies quickly after launch. The US filings, and their timing against the 2029 patents, are the signals Merck’s litigators will watch.

Merck is paying a premium for oncology outside PD-1

On 28 September Merck licensed SPR2015, a preclinical oral molecular-glue inhibitor of active KRAS G12D, from Shanghai-based SciBrunch Therapeutics for $400 million upfront and up to $2.13 billion in total, with a $400 million charge in the third quarter. The upfront is 18.8% of the headline, high for an asset with no human data. George Addona, senior vice president at Merck Research Laboratories, said it complements Merck’s pipeline of precision targeted candidates.

The licence follows the roughly $6.7 billion acquisition of cancer drug developer Terns Pharmaceuticals, which produced a $5.7 billion charge in the second quarter, and a March antibody discovery alliance with Infinimmune worth up to about $838 million. Business development head Sunil Patel said in early September that he expects a lot more deal flow, and Davis has called the years after 2028 more of a hill than a cliff. Merck told investors in January that it sees more than $70 billion of commercial opportunity from its pipeline by the mid-2030s.

Bispecifics could reach Keytruda’s lung franchise before biosimilars do

The sharpest near-term threat comes from a new class aimed at first-line non-small cell lung cancer, Keytruda’s largest market.

The deal values read as conviction. Bristol Myers Squibb and Pfizer each paid more than twice Merck’s upfront and are running head-to-head trials against Keytruda, while Merck, whose franchise is the target, has shown data from 11 treatment-naive patients. If a bispecific beats Keytruda in first-line lung cancer, that segment starts eroding before December 2028, and Qlex conversion protects nothing there.

Only one lane protects revenue after 2028 and sits fully in Merck’s hands

Set side by side, the lanes differ in what they protect and in who controls the outcome.

Conversion is the only lane that both protects revenue after 2028 and depends mainly on Merck’s own execution. The others expire with the patent, wait on courts and regulators, or sit years from revenue, which is why the strategy carries as much weight as it does on a single adoption curve.

What to watch

The FDA decision on ivonescimab in EGFR-mutated NSCLC, due on 14 November, the first US verdict on the PD-(L)1 x VEGF class. A positive decision gives Summit a US launch and a sales force before HARMONi-3 reports, and raises the pressure on Merck to show its hand on MK-2010.

The CMS final rule. Whether subcutaneous and intravenous versions are negotiated together decides whether Qlex shields the Medicare price in 2029 or only the biosimilar flank.

Qlex share at Merck’s third-quarter results. The path from double digits toward 30% to 40% by the end of 2027 is the best single measure of how much of Keytruda survives December 2028.

And Europe: the Commission’s KEYNOTE-B15 decision this quarter, and the point at which the Halozyme litigation lets Keytruda SC launch country by country.

The coverage counts Keytruda’s approvals. The number that decides Merck’s next five years is the share of US patients on a one-minute injection when the first biosimilar ships, and on Merck’s own target most of them will still be on the infusion.