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Keytruda (pembrolizumab) · anti-PD-1 · Merck & Co.
This page covers 1L MSI-H/dMMR metastatic colorectal cancer only (KEYNOTE-177), the CRC slice carved out of the tumor-agnostic MSI-H pool (KEYNOTE-158 covers non-CRC). Not the 1L NSCLC, melanoma or other Keytruda settings. See all Keytruda indications →
Label 1.9 reads simply: 'for the treatment of patients with unresectable or metastatic MSI-H or dMMR colorectal cancer (CRC) as determined by an FDA-authorized test.' The label carries NO line-of-therapy restriction, so the row's '1L' is narrower than the indication as written - pembrolizumab is not label-limited to first line in MSI-H CRC, even though KEYNOTE-177 was a first-line trial. Approved 2020-06-29 as a traditional approval from the outset. The separate older MSI-H CRC accelerated approval that sat under the tumour-agnostic entry was verified 2023-03-28.
All markets
2026 net revenue · modelled MSI-H CRC slice
$607M
CONCLUDED · 2026 modelled net revenue - indication slice, all markets; Merck & Co. reports no indication revenue. Modelled net revenue · sourced funnel
No model change since the 20 Sep 2026 snapshot.
The 15-second read
KEYNOTE-177 proved something bigger than its own revenue: that checkpoint monotherapy can replace chemotherapy outright in a biomarker-selected colorectal population (PFS 16.5 vs 8.2 months, HR 0.59, FDA Jun 2020). Commercially it is a focused, capped slice, only ~5% of metastatic CRC is MSI-H/dMMR, and it is at its ceiling right now: $607M in 2026 is the peak year, with erosion to $244M by 2034 as pembrolizumab's US composition-of-matter protection lapses around 2028 (EU ~2029). Two live pressures beyond the patent. BMS's nivolumab + ipilimumab (CheckMate-8HW) is a genuine chemo-free doublet challenger for the same first-line decision, and roughly 30% of these patients have primary resistance, the KEYNOTE-177 curves cross early before separating. The one thing that could still add patients is unglamorous: universal MSI/MMR testing is incomplete in community practice, so eligible patients are simply never identified.
Threats land:CheckMate-8HW's doublet takes the front-line decision on depth of response before the LOE arrives, so pembrolizumab enters biosimilar competition from a smaller base and the 2028–2030 fall is steeper than modelled.
Modelled path:Pembrolizumab holds its share of the 1L MSI-H mCRC pool through 2027 on Category 1 preferred standing, then erodes on schedule as biosimilars enter from ~2028 US and ~2029 EU, settling near $244M by 2034.
Levers land:Subcutaneous Keytruda Qlex (approved Sep 2025) converts enough volume into a defended formulation, and wider universal MSI/MMR testing identifies more eligible patients, so the post-LOE floor sits materially above the modelled tail.
The tested-and-treated fraction is the figure most at risk, an Ormeval scoping estimate sitting after the ~5% MSI-H/dMMR gate, capturing how completely community oncology actually runs universal MSI/MMR testing; the model itself calls testing completeness the key funnel leak, and unlike a share assumption it is a leak that could close.
At a glance
Mechanism anti-PD-1
Clinical
Commercial
Development to approval
These are regulatory approval dates (FDA/EMA/NMPA/PMDA), not commercial launch; launch follows after pricing & reimbursement (see the access-lag column in the HTA table). All four regulators have approved this indication. Cross-checked against Merck & Co. disclosures and regulator databases.
KEYNOTE-177 carved a defensible, high-value 1L niche out of the largest GI cancer, proving checkpoint monotherapy can replace chemotherapy entirely in a biomarker-selected colorectal subset, and reinforcing pembrolizumab's leadership across MSI-H disease. At a ~$0.7B modelled peak it is a focused slice, strategically important as the colorectal anchor of the MSI-H franchise and a proof point for biomarker-driven chemo-free oncology. It is now contested 1L by BMS's nivolumab-based chemo-free doublet (CheckMate-8HW) and exposed to the ~2028 biologic LOE.
About 5% of metastatic colorectal cancers are MSI-H/dMMR, a distinct, highly immune-responsive subset. KEYNOTE-177 (PFS 16.5 vs 8.2 mo; HR 0.59; FDA Jun 2020) made 1L pembrolizumab monotherapy the standard for these patients, displacing chemotherapy. A focused (~$0.7B modelled peak) but high-value slice; nivolumab±ipilimumab (CheckMate-8HW/-142) is the principal competitor, and BMS's chemo-free doublet is an increasingly strong 1L challenger.
Metastatic colorectal cancer is mostly microsatellite-stable (MSS) and immunotherapy-resistant, but the ~5% that are MSI-H/dMMR (deficient mismatch repair, high neoantigen load, often Lynch-associated) respond dramatically to checkpoint blockade. For this subset, KEYNOTE-177 showed 1L pembrolizumab monotherapy beats chemotherapy on PFS with durable responses and less toxicity, making it the chemo-free 1L standard. Across the 8 modelled markets ~12,000-15,000 patients/year are 1L MSI-H/dMMR mCRC, the pool this model sizes, gated by colorectal incidence, the metastatic fraction, the ~5% MSI-H rate, and testing completeness.
KEYNOTE-177 established pembrolizumab as the first-line standard of care for the ~5% of metastatic colorectal cancers that are MSI-H/dMMR, the first phase 3 win for checkpoint monotherapy over chemotherapy in 1L CRC. It roughly doubled progression-free survival (16.5 vs 8.2 months; HR 0.59) with a far better tolerability profile, defining a chemo-free 1L option for this molecularly-selected, immune-responsive subgroup.
Universal MSI/MMR testing in all colorectal cancer is guideline-recommended, testing completeness is the key funnel leak (incomplete in community settings). Only the ~5% MSI-H/dMMR subset is eligible; MSS disease is IO-resistant and excluded. Lynch-syndrome patients are enriched in this subset.
Randomized, open-label, active-controlled Phase 3; n=307; previously untreated unresectable/metastatic MSI-H/dMMR colorectal cancer; pembrolizumab 200 mg q3w vs investigator-choice chemotherapy (FOLFOX or FOLFIRI ± bevacizumab/cetuximab). Co-primary endpoints PFS and OS; crossover from chemo to pembrolizumab allowed (confounding OS).
Load-bearing 5/6 sourced. ASSUMED uptake is yours to change.
This indication only, not Keytruda's total revenue
First-line unresectable or metastatic MSI-H/dMMR colorectal cancer, pembrolizumab monotherapy (KEYNOTE-177), which doubled progression-free survival vs chemotherapy and became the 1L standard for this molecular subset. The branded Keytruda line is the monetized slice.
Reported actuals are always drawn and need no chip: a cited reported figure is a fact, not a claim. Everything forward of them is one of the 4 kinds above.
$607M
8 modelled markets (US, EU5, JP, CN) · modelled net revenue · 2026 (forecast)
Peak $607M · launch 2020 → 2034
modeled history (left of today)·click any year to decompose its funnel below.
Measured band: none - no measured band: n<8
Bull / bear elsewhere in the product are a sensitivity (fixed multipliers), not this band.
Pre-2026 figures are MODELLED and calibrated to Merck's reported Keytruda franchise (FY2025 ≈ $31.7B): the 1L MSI-H mCRC slice is a focused ~$0.7B line that rises from the 2020 approval to a ~$0.7B plateau, then erodes from ~2028 into the biosimilar cliff. The 'today' marker splits modelled history from forecast.
No reported anchor exists at this grain: companies publish this asset as one product line and never split it by indication × country, so every year above is modelled, including the years already past. The claims below are scored against reported actuals wherever a program has them.
A forecast year closes when an actual is reported for it. A miss is the distance from that actual, signed as the claim fell: under it, or over it.
| Claim | Closed years | Worst miss | Worst miss % |
|---|---|---|---|
| Ormeval modelMODELLED · Ormeval · live | - | no closed year yet | - |
A superseded team version keeps its own row: what it was off by is still a fact about that version. A row with no closed year is not a good score.
What it shows. A modelled base-case net-revenue curve for this indication, year by year, split at 'today' into modelled history and forecast, with the branded curve shown against its in-class rivals.
What to look for. The peak year and how steep the decline is after loss of exclusivity, and where a rival's curve crosses yours, that crossing is the share the model has you losing.
Common misread. Reading the pre-'today' portion as reported actuals (it's modelled), or treating the base case as a company target. It is one deterministic Ormeval-modelled scenario anchored to cited actuals, not guidance and not analyst consensus.
Key model assumptions · The headline rests on that testing-completeness estimate and on pembrolizumab's branded share of the 1L MSI-H pool against the nivolumab-based doublet, with an annual on-drug net derived from a ~$11.8k per 200 mg US ASP, Merck reports Keytruda as one ~$31.7B FY2025 franchise, so this indication's entire history is a modelled carve-out.
The decline is defended, not certain
The decline is anchored to a dated event, US pembrolizumab composition-of-matter expiry ~2028, EU ~2029, and is modelled gradually rather than as a cliff, which is right for a biologic; the genuine uncertainty is Qlex, since subcutaneous conversion could move volume into a defended presentation and make the post-2028 erosion of the branded line shallower than a pure IV-biosimilar assumption implies.
What would change our mind
If CheckMate-8HW's nivolumab + ipilimumab shows an overall-survival advantage in 1L MSI-H/dMMR mCRC, the endpoint KEYNOTE-177 could not deliver cleanly, its OS being confounded by 60% crossover, the modelled pembrolizumab share is too high and the decline should begin before the LOE rather than because of it; conversely, if universal MSI/MMR testing rates in US community oncology rise materially by 2028, the pool grows and the modelled peak year is wrong.
A scenario is your own assumptions layered on Ormeval’s cited baseline. We never change the baseline; save as many named scenarios as you like and click one to load it back later.
| Driver · 2026 | US | FR | DE | IT | ES | UK | JP | CN | Total | Source |
|---|---|---|---|---|---|---|---|---|---|---|
| Colorectal cancer incidence (2026) | 155k | 48k | 59k | 49k | 43k | 45k | 158k | 522k | 1.08M | GLOBOCAN 2022 |
New colorectal cancer cases per year; +0.5%/yr (rising early-onset offset by screening in older groups). Shown for 2026: 2024 basis +1%/yr → ×1.010. Country-specific GLOBOCAN 2022 colorectal cancer incidence; large across all markets, very large in China and Japan. +0.5%/yr (rising early-onset disease partly offset by screening in older populations). | ||||||||||
| × Metastatic (1L-eligible)est | 30% | 30% | 30% | 30% | 31% | 31% | 30% | 33% | share, not summed | SEER · registries |
Stage IV at diagnosis + recurrences progressing to metastatic, the 1L systemic-eligible fraction. About 20-22% of CRC presents de-novo Stage IV; adding earlier-stage recurrences that progress to metastatic disease, ~28-32% of incident CRC reaches 1L metastatic systemic therapy. Broadly consistent across markets; modestly higher where screening uptake is lower (later presentation). | ||||||||||
| × MSI-H/dMMR (~5%)est | 6% | 6% | 6% | 6% | 6% | 6% | 7% | 7% | share, not summed | Koopman · Le |
The MSI-H/dMMR fraction of metastatic CRC, the IO-eligible molecular subset (MSS disease is IO-resistant, excluded). MSI-H/dMMR is ~15% of early-stage CRC but only ~4-5% of METASTATIC CRC (MSI-H tumours metastasize less often). This ~5% is the entire IO-eligible pool; the ~95% MSS remainder is checkpoint-resistant and excluded. Held at ~5% across markets (slightly higher in East Asia per some series). | ||||||||||
| × Tested, fit, 1L IO-treatedest | 90% | 88% | 88% | 85% | 85% | 88% | 88% | 50% | share, not summed | testing audits |
Of MSI-H mCRC, those MSI/MMR-tested, fit for and receiving 1L checkpoint therapy. Branded pembrolizumab UPTAKE is the share row below. Combines MSI/MMR testing completeness (the key leak, universal testing is guideline-recommended but incomplete in community settings) and fitness for/receipt of 1L checkpoint therapy. High where reflex universal testing is routine (~0.85-0.90 West, Japan); lower in China (~0.50, testing/access tier-concentrated). Excludes pembrolizumab UPTAKE (the share layer below). | ||||||||||
| = Addressable 1L MSI-H mCRC pool | 2.5k | 762 | 931 | 756 | 682 | 739 | 2.7k | 5.6k | 15k | computed |
CRC incidence × metastatic fraction × ~5% MSI-H × tested/treated, 1L MSI-H/dMMR mCRC patients reachable for checkpoint therapy this year. The 1L MSI-H mCRC pool is stable-to-rising, expanding universal MSI/MMR testing identifies more eligible patients (captured in the tested/treated gate) and CRC incidence drifts up modestly (+0.5%/yr, incl. early-onset disease). Modelled flat at the pool level. | ||||||||||
| × Keytruda uptake (branded) | 69% | 67% | 69% | 63% | 46% | 47% | 38% | 28% | share, not summed | ASSUMED |
Per-market branded uptake of the addressable pool this year (launch ramp net of competitors & biosimilars). See the competitive curve below; pick a market for its access basis. | ||||||||||
| = Treated with Keytruda | 1.7k | 513 | 642 | 475 | 311 | 347 | 1.0k | 1.6k | 6.6k | computed · assumed input |
Addressable pool × branded uptake. | ||||||||||
| × Net price / patient (2026) | $173K | $91K | $96K | $86K | $77K | $85K | $67K | $24K | per patient, not summed | ASP · HTA · NHI |
Until-progression IO: per-patient revenue is the annual net cost while on-drug. US ASP ≈ $11.8k/200mg q3w (~$205k/yr list) net of ~10-15% GTN → ~$180k/yr. EU nets ~$80-100k. Japan ~$70k. China ~$25k. −2%/yr forward; held flat before 2024. SHOWN FOR 2026: the per-market figures in "Net pricing: assumptions & basis" below are the 2024 basis; this row applies -2%/yr from 2024 (×0.9604), so it is the same source value at a later date, not a second price. | ||||||||||
| = Net revenue / yrOutput | $297M | $46.8M | $61.6M | $41.0M | $23.9M | $29.3M | $69.7M | $37.3M | $607M | computed · assumed input |
Treated patients × realized net price. | ||||||||||
Regional revenue mix · 2026 modelled
Model estimate, sourced from the funnel table above
No reported competitor-share series exists for this setting, so every trajectory below is modelled from approval timing, label breadth and the funnel, not reported data.
In-class share, 1L MSI-H/dMMR colorectal immunotherapy: 8 modelled markets (US, EU5, JP, CN)
Each agent's share of the addressable 1L MSI-H mCRC pool. The branded-pembrolizumab line shows the launch ramp from the 2020 approval, then the ~2028 LOE erosion; the gap below the top line is patients on nivolumab-based regimens, chemotherapy, or untested/untreated. The branded pembrolizumab line (IV + SC Qlex) is the only line this model monetizes.
Share of the 15k-patient addressable 1L MSI-H mCRC pool this regimen is modelled to treat, by year
Keytruda is modelled at 45% of this pool in 2026, peaking at 45% in 2026; each point of share is revenue on the chart above.
Scope: 8 modelled markets (US, EU5, JP, CN) · follows the market selector above
Rivals' share, same pool
Nivolumab ± ipilimumab holds the largest rival share in 2026, 8% of the pool; that is the share Keytruda has to take or hold.
Rivals, rescaled - note the axis maximum (30%), which is smaller than the plot above. Same data, a linear axis of its own, so a low-share entrant is readable rather than a hairline on the baseline.
Launch ramp = approval timing (US Jun 2020); nivolumab+ipilimumab (CheckMate-142/-8HW) the principal competitor; pembrolizumab biosimilars timed to ~2028 US / ~2029 EU LOE. Competitor trajectories are stated assumptions.
Readouts, approvals and LOE events for pembrolizumab and its rivals in this setting. Estimated timing is flagged; confirmed dates cited from Merck & Co. disclosures and regulator databases.
Composition-of-matter expiry (~2028); pembrolizumab biosimilars erode the branded MSI-H CRC line
EU biosimilar entry; SC Qlex conversion mitigates share loss
✓ = reported public fact, cited. Upcoming timing is estimated from company guidance and trial registries, a projection, not a commitment. Approvals = US (FDA) · EU (EMA) · Japan (PMDA) · China (NMPA). ● = pembrolizumab, competitor tag = a same-setting rival.
Residual unmet need: why the field stays alive
Even in this immune-responsive subset, ~30% of MSI-H/dMMR mCRC patients have primary resistance and progress early on pembrolizumab monotherapy (the KEYNOTE-177 PFS curves cross early before separating durably), and there is no established post-checkpoint standard. Universal MSI/MMR testing is still incomplete in community settings (a real leak that leaves eligible patients unidentified), and the competing nivolumab+ipilimumab doublet may offer deeper responses for some, keeping the 1L choice genuinely contested.
The synthesis for this indication, grounded in the cited trial, guideline and access facts above.
Rivals in this setting (1L MSI-H/dMMR metastatic colorectal cancer)
Swipe to explore →
| Rival / regimen | Developer | Position in this setting | Approved (date, trial, n) | Head start vs this regimen (months) | Source |
|---|---|---|---|---|---|
| Nivolumab + ipilimumab (Live threat) | Bristol Myers Squibb | Live threatwhyStrong 1L PFS in MSI-H mCRC (CheckMate-8HW), the principal chemo-free doublet competitor; nivo entered the MSI-H CRC category first (2L, 2017) | not in the record | not in the record | CheckMate-8HW / CheckMate-142 |
| Nivolumab monotherapy (Watch) | Bristol Myers Squibb | WatchwhyApproved MSI-H CRC; a direct PD-1 alternative | not in the record | not in the record | CheckMate-8HW / CheckMate-142 |
| Domestic Chinese PD-1s (MSI-H CRC) (China rival) | Innovent / others | China rivalwhySome domestic PD-1s pursue MSI-H CRC, China-only share pressure | not in the record | not in the record | tumour-specific / NMPA |
| Keytruda Qlex (subcutaneous) (Merck & Co. pipeline) | Merck | Merck & Co. pipelinewhyFDA-approved Sep 2025, intra-brand LOE/convenience defense (monetized within the branded line) | Sep 2025, - | -63 (after) | - |
| Pembrolizumab biosimilars (Watch) | Generic (post-LOE) | WatchwhyUS LOE ~2028; EU ~2029, erosion of the branded MSI-H CRC line | not in the record | not in the record | pembrolizumab composition-of-matter LOE ~2028 (US) |
Not every rival is approved in every region, so a share here is the modelled position in the markets where it competes, not a global one.
Net pricing: assumptions & basis
Pembrolizumab is dosed 200 mg q3w (or 400 mg q6w) IV, or via subcutaneous Qlex (Sep 2025), until progression or 35 cycles (~2-year cap), so per-patient revenue is the annual net cost while on-drug. US ASP ~$11.8k per 200 mg; net prices below are per-market.
Figures below are 2024 net prices, the basis the model is anchored on. The funnel applies -2%/yr from 2024, so the price it consumes for a later year is lower than the figure quoted here. Both come from this one value; the funnel row states the year it is showing.
Pembrolizumab is dosed 200 mg q3w (or 400 mg q6w) IV, or as SC Qlex (FDA Sep 2025), until progression or a 35-cycle (~2-year) cap, so per-patient revenue is the annual net cost while on treatment. US ASP ≈ $11,795/200 mg q3w (~$205k/yr list) ⇒ ~$180k/yr net after ~10-15% GTN. EU nets HTA-negotiated (~$80-100k). Japan NHI ~$70k. China low-reach/access-limited (~$25k). −2%/yr forward; held flat before 2024. ALL net prices are ESTIMATES.
What it shows. The approval-to-reimbursement journey by market: when each payer granted access, on what terms (PD-L1 or comparator restrictions), and the lag between regulatory approval and reimbursed revenue.
What to look for. The access-lag column, approval is not revenue and some markets take a year or more. And the restrictions that narrow the eligible population below the full label.
Common misread. Assuming a US price or approval transfers to other markets. Ex-US payers benchmark against comparators and reference prices, so the net price and the covered population are usually smaller.
Rows ordered by access speed. The approval→reimbursement lag is commercially load-bearing, and it is not one number per drug: a monotherapy indication and a later combination extension file separately with a payer and can reach routine commissioning years apart, even within the same asset’s first-line setting.
| Market | HTA body | Decision | Access lag | PD-L1 | Comparator | Key outcome / MEA note |
|---|---|---|---|---|---|---|
| US | FDA | 29 Jun 2020 (1L MSI-H mCRC) | reference | MSI-H/dMMR | Chemotherapy | Medicare Part B (J9271); biomarker-gated 1L coverage |
| Germany | G-BA / IQWiG | 2021 | ~0.4 yr | MSI-H/dMMR | Chemotherapy | Reimbursed; AMNOG net below list; densest EU access |
| UK | NICE TA709 | 2021 | ~1 yr | MSI-H/dMMR | Chemotherapy | Recommended 1L MSI-H/dMMR mCRC; confidential PAS |
| France | HAS | 2021 | ~0.6 yr | MSI-H/dMMR | Chemotherapy | Early access then reimbursement; SMR important |
| Italy | AIFA | 2021-2022 | ~1.5 yr | MSI-H/dMMR | Chemotherapy | Class H; managed entry; +regional formulary lag |
| Spain | SEFH / MoH | 2022 | ~2 yr | MSI-H/dMMR | Chemotherapy | Financed 1L; +17-region formulary lag |
| Japan | PMDA / NHI | 2021 | ~0.5 yr | MSI-H/dMMR | Chemotherapy | NHI-listed; routine MSI testing; biennial price cuts |
| China | NMPA | 2022-2023 | ~2.5 yr | MSI-H/dMMR | Chemotherapy | Approved; testing/access-limited; domestic PD-1 competition |
How much each assumption could move the forecast, one at a time, over the same cited baseline.
This is a sensitivity illustration, not a probability: it shows how far each assumption could move the forecast, never how likely it is.
Set a target and solve for one lever, what it would have to reach, benchmarked against real comparable launches.
One lever at a time: the other assumptions stay at baseline, so the trade-off stays visible.
A model that shows where its own risk is, not a number to trust. Never investment advice.
Cite this forecast as recorded on Q2 2026 → A permanent record of these figures that does not change when the model does.
Every reported figure here traces to a public source below; the model's own assumptions are labelled where they appear.
Reported figures are public facts from company filings; the forward peak is Ormeval's own modelled estimate, not company guidance and not analyst consensus. Approval and readout dates are cross-checked against public regulator and company disclosures. Not investment advice.