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Keytruda (pembrolizumab) · anti-PD-1 · Merck & Co.
This page covers the BCG-unresponsive high-risk NMIBC with CIS indication only (KEYNOTE-057 cohort A, pembrolizumab monotherapy), not muscle-invasive bladder cancer, not 1L advanced urothelial, and not other Keytruda settings. See all Keytruda indications →
Label 1.7: 'KEYTRUDA, as a single agent, is indicated for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.' The row's 'BCG-unresponsive high-risk NMIBC (CIS)' is accurate. Two gates worth carrying into any model: CIS must be present (papillary-only disease is out of label), and the patient must be cystectomy-ineligible or have declined cystectomy - a materially smaller population than all BCG-unresponsive NMIBC. Approved 2020-01-08 as a traditional approval; absent from all three accelerated-approval registries. No EU extension of indication on the EPAR as of 2026-09-16.
All markets
2026 net revenue · modelled; competitor erosion
$202M
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
This niche has already peaked and the model does not pretend otherwise: $295M in 2024, $202M today, $73M by 2034. KEYNOTE-057 was a genuine landmark, the first systemic immunotherapy approved in non-muscle-invasive bladder cancer, but 41% complete response with a 16.2-month median duration is now the weakest number in the room, against nadofaragene firadenovec at 51% (FDA Dec 2022) and Anktiva+BCG at 62% (FDA Apr 2024), both delivered intravesically rather than systemically. The indication is also structurally capped: the EMA application was withdrawn, so EU5 is modelled at zero and the pool is US plus Japan only. Two forces then compound, share loss to higher-CRR local entrants through the late 2020s, and pembrolizumab's ~2028 US biologic LOE on top of it. This is a small, closing line item within a ~$31.7B franchise, and the page's job is to show how quickly a first-mover niche unwinds when the efficacy bar moves.
Threats land:TAR-200 (J&J) converts its pending approval into guideline placement around 2026 and takes the cystectomy-avoidance patients on top of nadofaragene and Anktiva, so branded pembrolizumab's share of the BCG-unresponsive CIS pool collapses before the 2028 LOE rather than after it, and the $73M 2034 floor proves generous.
Modelled path:Branded pembrolizumab keeps a shrinking minority of the US and Japan BCG-unresponsive CIS pool as higher-CRR intravesical options take the responders, then biosimilars from ~2028 accelerate the fall from $202M today to $73M in 2034.
Levers land:Subcutaneous pembrolizumab (Qlex, Sep 2025) makes systemic delivery convenient enough to hold the cystectomy-unfit and instillation-averse segment, and Japan plus other ex-EU markets sustain the residual line above the modelled floor even after biosimilar entry.
The size of the addressable pool itself, the funnel of bladder-cancer incidence × ~75% high-risk NMIBC × ~7% BCG-unresponsive-CIS-and-bladder-sparing-eligible is an Ormeval scoping estimate calibrated backwards to a ~$0.3B peak, not an observed patient census. Merck reports Keytruda as one franchise line and never discloses NMIBC revenue, so no part of this curve is separately reported.
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-057 was a landmark, the first systemic immunotherapy approved in non-muscle-invasive bladder cancer, extending Keytruda into earlier-stage, bladder-sparing disease. Commercially, though, it is a niche (~$0.3B modelled peak): the BCG-unresponsive CIS pool is small, the regimen is US/Japan-only (NOT EU-approved, the EMA application was withdrawn), and intravesical competitors (nadofaragene firadenovec CRR 51%, Anktiva+BCG CRR 62%) report higher response rates with local rather than systemic delivery, pressuring share. Like the rest of the franchise it carries the ~2028 US biologic LOE.
BCG-unresponsive high-risk NMIBC with CIS is a small bladder-sparing niche where cystectomy was the only standard. Pembrolizumab monotherapy (KEYNOTE-057 cohort A) showed a 41% complete-response rate (median DOR 16.2 mo), the first systemic IO approval in NMIBC (FDA 8 Jan 2020). NOT EU-approved (EMA application withdrawn); Japan approved. A niche line (~$0.3B modelled peak) now contested by higher-CRR entrants, nadofaragene firadenovec (Adstiladrin, FDA Dec 2022, CRR 51%) and N-803/Anktiva+BCG (FDA Apr 2024, CRR 62%), plus gem/docetaxel and the pending TAR-200.
About 75% of bladder cancer presents non-muscle-invasive (NMIBC), and intravesical BCG is the standard for high-risk disease. A subset becomes BCG-unresponsive, and within that, patients with carcinoma in situ (CIS) who are unfit for or decline radical cystectomy are the KEYNOTE-057 population. This is a small slice: high-risk NMIBC with CIS that has failed BCG and is bladder-sparing-eligible. Pembrolizumab monotherapy delivered a 41% complete-response rate (median DOR 16.2 months), the first systemic IO approval here (FDA Jan 2020). Across the modelled markets the addressable BCG-unresponsive CIS pool is genuinely small; the indication is US- and Japan-centric (NOT EU-approved), and competition from intravesical entrants with higher CRRs limits pembrolizumab's share.
KEYNOTE-057 (cohort A) tested single-agent pembrolizumab in BCG-unresponsive high-risk NMIBC with carcinoma in situ, a setting where radical cystectomy was the only standard and many patients are unfit for or decline it. A complete response rate of 41% (median duration 16.2 months) supported the first systemic-immunotherapy approval in NMIBC (FDA, Jan 2020), offering a bladder-sparing alternative. It is a genuine but small niche, now contested by newer bladder-sparing entrants (nadofaragene firadenovec, N-803/Anktiva+BCG) with higher reported response rates.
Eligibility is BCG-unresponsive high-risk NMIBC with CIS in patients ineligible for or declining radical cystectomy. US- and Japan-centric (NOT EU-approved). Competition from intravesical entrants with higher CRRs (nadofaragene 51%, Anktiva+BCG 62%) and the pending TAR-200 limits uptake.
Single-arm, open-label Phase 2 (KEYNOTE-057, cohort A); n=101; BCG-unresponsive high-risk NMIBC with carcinoma in situ (± papillary tumours), ineligible for or declining radical cystectomy; pembrolizumab 200 mg q3w for up to 24 months. Primary endpoint complete response rate at 3 months; key secondary duration of response.
Load-bearing 4/5 sourced. ASSUMED uptake is yours to change.
This indication only, not Keytruda's total revenue
Pembrolizumab monotherapy in BCG-unresponsive, high-risk non-muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), with or without papillary tumours, in patients ineligible for or declining cystectomy (KEYNOTE-057 cohort A). A niche bladder-sparing option; FDA approved 8 Jan 2020. NOT EU-approved. 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.
$202M
8 modelled markets (US, EU5, JP, CN) · modelled net revenue · 2026 (forecast)
Peak $295M · launch 2018 → 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 BCG-unresponsive NMIBC slice is a small niche (~$0.3B modelled peak ~2024), a US/Japan-only line (NOT EU-approved) that peaks early and erodes as higher-CRR intravesical entrants (nadofaragene 2022, Anktiva+BCG 2024) take share and the ~2028 LOE bites. 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 soft inputs are the ~7% BCG-unresponsive-CIS gate that sizes the pool and pembrolizumab's declining share of it against nadofaragene and Anktiva, both are judgement calls; the price side is comparatively firm (US ASP ~$11.8k per 200 mg dose, up to a 24-month course, Japan at NHI), and EU and China are simply zeroed because the indication is not approved there.
The decline is defended, not certain
The fall from the 2024 peak is driven by two independently verifiable things rather than one guess, higher-CRR competitors already approved (51% and 62% versus 41%) and a ~2028 US composition-of-matter LOE, which is why it is defended. It is not certain: the model assumes share loss tracks the CRR gap, but in a cystectomy-avoidance setting clinicians often sequence rather than substitute, and a residual systemic option after intravesical failure could hold volume better than the curve allows.
What would change our mind
The base case is wrong if pembrolizumab retains guideline-recommended first-choice status in BCG-unresponsive CIS after TAR-200's expected approval, AUA/NCCN placement is the observable trigger, and if the systemic option stays ahead of the intravesical ones in the algorithm past 2027, the modelled share decline is too steep. Conversely, an EU approval would falsify the model's zeroing of the EU5 pool outright and reset the ceiling, though the withdrawn EMA application makes that unlikely.
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 |
|---|---|---|---|---|---|---|---|---|---|---|
| Bladder cancer incidence (2026) | 84k | 13k | 30k | 29k | 22k | 21k | 23k | 94k | 317k | ACS · GLOBOCAN 2022 |
New bladder-cancer cases/yr; the BCG-unresponsive high-risk NMIBC-with-CIS subset is the addressable pool. Shown for 2026: 2024 basis +1%/yr → ×1.010. Country-specific GLOBOCAN 2022 bladder-cancer incidence; the KEYNOTE-057-addressable pool is the small BCG-unresponsive high-risk NMIBC-with-CIS subset (see rates). +0.5%/yr ageing. | ||||||||||
| × High-risk NMIBCest | 75% | 75% | 75% | 75% | 75% | 75% | 73% | 70% | share, not summed | literature (~75%) |
Non-muscle-invasive (~75% of bladder cancer); the high-risk subset that receives BCG. About three-quarters of bladder cancer presents non-muscle-invasive; the high-risk subset (high-grade T1, CIS, large/multifocal Ta) is treated with intravesical BCG and is the source of the BCG-unresponsive pool. | ||||||||||
| × BCG-unresponsive CIS, bladder-sparing-eligibleest | 7% | 7% | 7% | 7% | 7% | 7% | 7% | 6% | share, not summed | derived (BCG-unresp. CIS) |
Of NMIBC, the small BCG-unresponsive high-risk-with-CIS subset, cystectomy-unfit/declining (KEYNOTE-057-eligible). A narrow funnel within NMIBC: only high-grade BCG-treated patients who become BCG-unresponsive, have CIS, and are unfit for or decline cystectomy are KEYNOTE-057-eligible. Modelled at ~0.07 of NMIBC (~0.06 China), the key niche-sizing judgement, calibrated to a ~$0.3B peak. | ||||||||||
| = Addressable BCG-unresponsive CIS pool | 4.4k | 689 | 1.6k | 1.5k | 1.2k | 1.1k | 1.2k | 3.9k | 16k | computed |
Bladder incidence × high-risk NMIBC × BCG-unresponsive-CIS & bladder-sparing-eligible, a small niche; US + Japan only (NOT EU-approved). The BCG-unresponsive CIS pool is small and stable. Revenue is constrained less by pool size than by the closed EU markets (NOT approved), the competitive entry of higher-CRR intravesical agents (nadofaragene 2022, Anktiva 2024), and the ~2028 biologic LOE, so the line peaks early (~2024) and declines. | ||||||||||
| × Keytruda uptake (branded) | 23% | 0% | 0% | 0% | 0% | 0% | 40% | 0% | 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 | 1.0k | 0 | 0 | 0 | 0 | 0 | 475 | 0 | 1.5k | computed · assumed input |
Addressable pool × branded uptake. | ||||||||||
| × Net price / patient (2026) | $168K | $91K | $96K | $86K | $77K | $85K | $67K | $24K | per patient, not summed | ASP · NHI |
Pembrolizumab 200 mg q3w for up to 24 months: per-patient annual revenue ≈ one year of net cost. US ASP ≈ $11.8k/200mg q3w (~$205k/yr list) net of GTN → ~$175k. Japan NHI ~$70k. EU/China zero (NOT approved). −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 | $170M | $0 | $0 | $0 | $0 | $0 | $31.9M | $0 | $202M | 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, BCG-unresponsive NMIBC with CIS: 8 modelled markets (US, EU5, JP, CN)
Each agent's share of the addressable BCG-unresponsive CIS pool (US + Japan; EU markets are zero, NOT approved). The branded pembrolizumab line ramps from the 2020 launch, peaks early (~2024), then loses share to nadofaragene (2022) and Anktiva+BCG (2024) and erodes from the ~2028 LOE. The branded pembrolizumab line is the only one this model monetizes.
Share of the 16k-patient addressable BCG-unresponsive CIS pool this regimen is modelled to treat, by year
Keytruda is modelled at 10% of this pool in 2026, peaking at 12% in 2024; 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
N-803 / Anktiva + BCG holds the largest rival share in 2026, 4% of the pool; that is the share Keytruda has to take or hold.
Rivals, rescaled - note the axis maximum (5%), 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 = FDA Jan 2020 (US) + Japan ~2021; EU zero (NOT approved). Competitor entry: nadofaragene (Dec 2022, CRR 51%), Anktiva+BCG (Apr 2024, CRR 62%). Pembrolizumab biosimilars timed to ~2028 US LOE. Competitor trajectories and pembro's share 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.
TAR-200 (intravesical gemcitabine system, J&J), pending/expected approval; further pressures the niche
Pembrolizumab composition-of-matter expiry (~2028); biosimilars erode the branded NMIBC niche
✓ = 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
Pembrolizumab's 41% complete-response rate leaves the majority of BCG-unresponsive CIS patients without durable benefit, and systemic anti-PD-1 toxicity is a meaningful trade-off for non-muscle-invasive disease versus intravesical options. There is no EU approval, no biomarker for selection, and durability beyond ~16 months is limited, sustaining intense competition (nadofaragene, Anktiva+BCG, gem/docetaxel, the pending TAR-200) and continued cystectomy for many.
The synthesis for this indication, grounded in the cited trial, guideline and access facts above.
Rivals in this setting (BCG-unresponsive high-risk NMIBC with CIS)
Swipe to explore →
| Rival / regimen | Developer | Position in this setting | Approved (date, trial, n) | Head start vs this regimen (months) | Source |
|---|---|---|---|---|---|
| Nadofaragene firadenovec (Adstiladrin) (Live threat) | Ferring | Live threatwhyFDA-approved Dec 2022 for BCG-unresponsive NMIBC with CIS; CRR 51%, higher than pembrolizumab; intravesical (quarterly). | Dec 2022, Study CS-003 | -35 (after) | Adstiladrin (nadofaragene firadenovec), FDA approval Dec 2022, CRR 51% |
| N-803 / Anktiva + BCG (Live threat) | ImmunityBio | Live threatwhyFDA-approved Apr 2024; CRR ~62%, the highest reported response in BCG-unresponsive CIS. | Apr 2024, QUILT-3.032 | -51 (after) | Anktiva (FDA Apr 2024) |
| Gemcitabine + docetaxel (sequential intravesical) (Live threat) | Generic / academic | Live threatwhyCheap, widely used intravesical doublet for BCG-unresponsive NMIBC; guideline-recognized. | not in the record | not in the record | Retrospective / SWOG |
| TAR-200 (intravesical gemcitabine system) (Watch) | Johnson & Johnson | WatchwhyPending/expected approval (~2026), high CRRs in BCG-unresponsive CIS; a major emerging competitor. | not in the record | not in the record | SunRISe-1 |
| Pembrolizumab biosimilars (Watch) | Generic (post-LOE) | WatchwhyUS LOE ~2028, erodes the branded NMIBC niche. | not in the record | not in the record | pembrolizumab composition-of-matter LOE ~2028 |
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 IV (or SC Qlex from Sep 2025) for up to 24 months, so per-patient annual revenue is ~one year of net cost. US ASP ~$11.8k per 200 mg; Japan NHI net below. EU/China prices are placeholders, the indication is NOT approved there (zero penetration).
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 in BCG-unresponsive NMIBC is 200 mg q3w (IV or SC Qlex) for up to 24 months. US ASP ≈ $11,795/200 mg q3w (~$205k/yr list) ⇒ ~$175k net after GTN. Japan NHI ~$70k. The EU markets and China carry placeholder prices but ZERO penetration, the indication is NOT approved there (EMA application withdrawn; no China NMIBC approval). −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 | 8 Jan 2020 (BCG-unresponsive NMIBC CIS) | reference | None | Single-arm (CRR) | Medicare Part B (J9271); the anchor market, but contested by nadofaragene (2022) and Anktiva+BCG (2024) |
| Germany | G-BA / EMA | NOT approved | n/a | None | - | NOT EU-approved, EMA application withdrawn; no German access for this indication |
| UK | NICE / MHRA | NOT approved | n/a | None | - | NOT approved for this indication; no UK access |
| France | HAS / EMA | NOT approved | n/a | None | - | NOT EU-approved; no French access for this indication |
| Italy | AIFA / EMA | NOT approved | n/a | None | - | NOT EU-approved; no Italian access for this indication |
| Spain | SEFH / EMA | NOT approved | n/a | None | - | NOT EU-approved; no Spanish access for this indication |
| Japan | PMDA / NHI | Approved (~2021) | ~1.5 yr | None | Single-arm (CRR) | PMDA-approved; NHI-listed, the second meaningful market after the US |
| China | NMPA | Not approved (this indication) | n/a | None | - | Not approved for NMIBC; no China access for this indication |
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.