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Keytruda (pembrolizumab) · anti-PD-1 + BCG · Merck & Co.
This page covers the high-risk NMIBC BCG-combination indication only (the KEYNOTE-676 program), not the full Keytruda franchise. Pembrolizumab is already approved (2020) as monotherapy for BCG-unresponsive CIS (KEYNOTE-057); KEYNOTE-676 is the BCG-combination, earlier-line expansion. See all Keytruda indications →
NCT03711032; pembro + BCG vs BCG; CR in CIS.
All markets
Pre-approval, revenue is a conditional scenario
$467M
CONCLUDED · modelled net revenue - indication slice, all markets; Merck & Co. reports no indication revenue. Modelled scenario · assumes approval · not guidance
No model change since the 20 Sep 2026 snapshot.
The 15-second read
The awkward arithmetic of this page is that the modelled launch year and the molecule's loss of exclusivity are the same year. Pembrolizumab IV composition-of-matter protection lapses around 2028 in the US, and KEYNOTE-676 is modelled to launch ~2028, ramp to a $467M peak in 2031, then fall to $364M by 2034 as subcutaneous pembrolizumab and biosimilars erode the molecule underneath the indication. Strategically the move makes sense, it takes Keytruda from a narrow BCG-unresponsive CIS monotherapy niche (KEYNOTE-057, CR 41%, approved 2020) into first-line, BCG-combination high-risk NMIBC, an earlier, larger, longer-duration, urology-managed pool. The unresolved clinical question is whether a systemic checkpoint inhibitor earns its toxicity in an organ-confined, largely curable disease when the competing approaches (TAR-200, Anktiva, nadofaragene, cretostimogene) all deliver into the bladder itself. That readout is close: primary completion is estimated Jul 2026.
Threats land:Cohort B's event-free-survival benefit in BCG-naïve patients is modest, and urologists decline to add IV immunotherapy with systemic immune-related toxicity to BCG in early organ-confined disease when TAR-200 and cretostimogene offer bladder-local delivery with high complete-response rates, approval into a niche, not a first line.
Modelled path:KEYNOTE-676 reads out positive around mid-2026 on at least one cohort, pembrolizumab plus BCG launches ~2028 into an already-crowded novel-agent field as the last entrant, peaks at $467M in 2031, and then declines as the molecule itself genericises.
Levers land:A strong Cohort B EFS result makes pembrolizumab plus BCG the new BCG-naïve standard rather than an add-on option, and because that cohort is the largest slice of high-risk NMIBC, the indication captures more of the ~55k addressable patients a year than the modelled category-penetration share allows.
Pembrolizumab plus BCG's share of the BCG-treated, regimen-fit high-risk NMIBC pool is the figure most at risk, an Ormeval scoping estimate for an unread-out trial entering last against four novel agents, and applied on top of a category-penetration assumption about how many high-risk patients receive any novel add-on at all.
At a glance
Mechanism anti-PD-1 + BCG
Clinical
Commercial
Development to approval
This indication is not yet approved: the phases show development stage and regulatory approval is expected, not granted (2028). Per-market timing is modelled from the Phase 3 readout plus standard regulatory lags (US/EU ~1 yr; Japan/China ~2 yr), an estimate, not company guidance. Status cross-checked against Merck & Co. disclosures and trial registries.
KEYNOTE-676 would push Keytruda upstream from its narrow BCG-unresponsive CIS monotherapy niche (KEYNOTE-057, 2020) into the much larger FIRST-LINE, BCG-combination high-risk NMIBC population, an early-disease, long-duration, urology-managed setting. It is one of several Merck moves to entrench Keytruda across the genitourinary continuum ahead of the 2028 US composition-of-matter LOE. Strategically the prize is durable, earlier-line volume; the risk is a crowded and fast-moving NMIBC field (TAR-200, Anktiva, nadofaragene, cretostimogene) and the open question of whether a systemic anti-PD-1 adds enough on top of BCG to justify the cost and toxicity in an organ-confined, largely curable disease.
High-risk NMIBC (high-grade Ta, any T1, and/or CIS) is bladder cancer confined to the mucosa/lamina propria but with a high risk of recurrence (~60–80% at 5 yr) and progression to muscle-invasive disease. Standard of care is TURBT + intravesical BCG, but many patients recur or fail BCG. KEYNOTE-676 tests pembrolizumab + BCG in both the post-BCG-induction (persistent/recurrent) and BCG-naïve settings. The pivotal readout is not yet public, this page is a PRE-APPROVAL conditional scenario, not a reported result.
Non-muscle-invasive bladder cancer (NMIBC) is ~70–75% of all bladder cancer at diagnosis (Ta, T1, CIS). Within NMIBC, the AUA/EAU high-risk group, high-grade Ta, any T1, and/or CIS, is roughly 40% of NMIBC and carries the greatest recurrence/progression risk, which is why it is treated with intravesical BCG after TURBT. BCG remains the backbone, but recurrence and BCG failure are common, and a wave of new agents (pembrolizumab, TAR-200, N-803/Anktiva, nadofaragene, cretostimogene) is entering both the BCG-unresponsive and, via combination trials like KEYNOTE-676, the BCG-naïve first-line setting. Across the modelled markets roughly 55,000 high-risk NMIBC patients per year start BCG-based therapy and could be addressable for a BCG-combination regimen; this is a specialized, urology-office segment, not a broad oncology market.
KEYNOTE-676 (NCT03711032) is a Phase 3, randomized, comparator-controlled trial testing whether adding pembrolizumab to standard intravesical BCG improves outcomes in high-risk NMIBC, both after BCG induction (persistent/recurrent, Cohort A, primary endpoint complete-response rate) and in BCG-naïve patients (Cohort B, primary endpoint event-free survival). It is Merck's move to bring Keytruda into the FIRST-LINE / BCG-combination NMIBC setting, beyond its existing BCG-unresponsive CIS monotherapy label (KEYNOTE-057). As of mid-2026 the pivotal readout is NOT public (primary completion estimated Jul 2026), so no efficacy figure is asserted here; the clinical section is design/method-only and the revenue line is a labelled scenario contingent on a positive readout and approval.
Pembrolizumab is ALREADY guideline-listed as MONOTHERAPY for BCG-unresponsive CIS (KEYNOTE-057, 2020). KEYNOTE-676 tests the earlier-line BCG-COMBINATION use, which is not yet in guidelines pending the pivotal readout.
Randomized, comparator-controlled Phase 3 in high-risk NMIBC (high-grade Ta, any T1, and/or CIS). Cohort A (persistent/recurrent after BCG induction): pembrolizumab 200 mg IV Q3W + BCG vs BCG monotherapy; primary endpoint complete-response rate by blinded independent central review. Cohort B (BCG-naïve or BCG-remote >2 yr): pembrolizumab 400 mg IV Q6W + BCG (reduced-maintenance Arm B-1 or full-maintenance Arm B-2) vs BCG monotherapy (Arm B-3); primary endpoint event-free survival. Estimated enrollment 1,397; sponsor Merck Sharp & Dohme. Start Dec 2018; primary completion estimated Jul 2026; study completion estimated Nov 2034.
Pre-approval · Phase III · conditional scenario
This indication is not approved. The revenue below is a modelled scenario that assumes approval and launch around 2028, every input (epidemiology, trial, pricing) is cited, but the approval itself is uncertain. It is an estimate, not guidance and not a reported figure. Read the pivotal-trial and development-timeline sections below for the regulatory basis.
Load-bearing 0/1 sourced. ASSUMED uptake is yours to change.
PRE-APPROVAL SCENARIO, KEYNOTE-676 has not read out (primary completion est. Jul 2026). Revenue below is a labelled conditional forecast contingent on positive Cohort A/B data and regulatory approval, NOT a reported result.
This indication only, not Keytruda's total revenue
Pembrolizumab added to intravesical BCG in high-risk non-muscle-invasive bladder cancer (HR-NMIBC): Cohort A = persistent/recurrent HR-NMIBC after BCG induction (pembrolizumab 200 mg IV Q3W + BCG vs BCG alone); Cohort B = BCG-naïve HR-NMIBC (pembrolizumab 400 mg IV Q6W + BCG, reduced or full maintenance, vs BCG alone). High-grade Ta, any T1, and/or carcinoma in situ (CIS). PRE-APPROVAL, forecast is a conditional scenario.
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.
$0
8 modelled markets (US, EU5, JP, CN) · modelled net revenue · 2026 (forecast)
Peak $467M · launch 2028 → 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.
This is a PRE-APPROVAL scenario for a NEW Keytruda indication (first-line/BCG-combination high-risk NMIBC). Merck reports Keytruda as one product line, never by indication × country, so there is no reported history for this use, every year shown is a forward, conditional model with zero revenue before the estimated ~2028 launch.
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 softest inputs are the funnel gates and the price. Getting from bladder-cancer incidence to the addressable pool requires three estimated fractions in a row (NMIBC ~70–75%, high-risk ~40%, BCG-treated and fit ~55%), and per-patient revenue is the standard Keytruda molecule net (~$11.8k per 200 mg) multiplied by an assumed ~1-year course to ~$150k US, with no indication-specific net price disclosed anywhere.
The decline is defended, not certain
The post-2031 decline is defended by a dated, molecule-level event rather than anything about NMIBC: US pembrolizumab IV composition-of-matter exclusivity lapses ~2028, and subcutaneous pembrolizumab plus biosimilars erode the molecule across the window. It is not certain in shape, the model treats it as a gentle taper, whereas an IV monoclonal facing biosimilars typically loses branded volume much faster, and conversely a successful subcutaneous conversion that biosimilars cannot match would keep this line flatter than shown.
What would change our mind
The base case is wrong if KEYNOTE-676's Cohort B EFS endpoint fails to separate from BCG alone when the trial reaches its estimated Jul 2026 primary completion, Cohort A alone would only re-cover the post-BCG population Keytruda already has a label in, which is not the pool this model sizes. It is separately wrong if TAR-200 secures a BCG-naïve high-risk NMIBC approval before 2028, because the model already puts pembrolizumab last into this field and a bladder-local rival owning the frontline would leave no room for the modelled share.
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 | 85k | 13k | 30k | 29k | 22k | 21k | 23k | 93k | 316k | ACS · GLOBOCAN 2022 |
New bladder-cancer cases/yr; ~75% male, highest ASR in Southern/Western Europe. Bladder cancer is the 9th most common cancer (~614k/yr globally). Same incidence base as the NIAGARA (MIBC) model in this file; ~+0.5%/yr for ageing demographics. | ||||||||||
| × Non-muscle-invasiveest | 75% | 75% | 75% | 75% | 75% | 75% | 73% | 70% | share, not summed | literature (~75%) |
NMIBC (Ta, T1, CIS) vs muscle-invasive at diagnosis. About three-quarters of bladder cancer presents non-muscle-invasive (the complement of the ~25% MIBC used in the NIAGARA model). Slightly lower in China/Japan (later presentation). | ||||||||||
| × High-risk (HG Ta / T1 / CIS)est | 40% | 40% | 40% | 40% | 40% | 40% | 40% | 42% | share, not summed | AUA/EAU (~40%) |
AUA/EAU high-risk NMIBC (high-grade Ta, any T1, and/or CIS), the BCG-treated group. Within NMIBC, the AUA/SUO & EAU high-risk group (high-grade Ta, any T1, and/or CIS) is roughly 40% of cases and is the population treated with intravesical BCG. Modelled at ~40% across markets; the softest funnel input. | ||||||||||
| × BCG-treated / regimen-fitest | 55% | 55% | 55% | 55% | 55% | 55% | 55% | 40% | share, not summed | modelled estimate |
Of high-risk NMIBC, those who start BCG-based therapy and are fit for a BCG-combination regimen (vs upfront cystectomy, low-volume watchful waiting, or BCG-shortage exclusion). Most high-risk NMIBC is treated with intravesical BCG after TURBT, but a share go to upfront cystectomy, are unfit, or are limited by chronic BCG supply shortages. Modelled at ~55% reaching a BCG-combination-eligible pool (lower in China where BCG access and practice patterns differ). | ||||||||||
| = Addressable high-risk NMIBC pool | 14k | 2.1k | 5.0k | 4.8k | 3.6k | 3.5k | 3.7k | 11k | 48k | computed |
Incidence × the rates above, high-risk NMIBC (high-grade Ta, any T1, and/or CIS) patients who start BCG-based therapy and are fit for a BCG-combination regimen this year. A specialized urology-office segment. The high-risk NMIBC pool drifts up modestly with ageing demographics and rising bladder-cancer incidence; intravesical-delivery competitors (TAR-200, N-803) shape share rather than the pool size. | ||||||||||
| × Keytruda uptake (branded) | 0% | 0% | 0% | 0% | 0% | 0% | 0% | 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 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | computed · assumed input |
Addressable pool × branded uptake. | ||||||||||
| × Net price / patient | $150K | $70K | $78K | $62K | $45K | $68K | $72K | $40K | per patient, not summed | derived (course-adj.) |
Pembrolizumab list is ~$11.8k per 200 mg (Q3W) in the US; a ~1-year course (≈17 Q3W or ≈9 Q6W doses) grosses ~$110k ASP, modelled at ~$150k realized after the BCG-combination course but well below metastatic multi-year exposure. Ex-US nets are lower per published tariffs. −4%/yr forward; all figures modelled and flagged. | ||||||||||
| = Net revenue / yrOutput | $0 | $0 | $0 | $0 | $0 | $0 | $0 | $0 | $0 | 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.
Novel-agent share of high-risk NMIBC (scenario): 8 modelled markets (US, EU5, JP, CN)
Each agent's share of the addressable high-risk NMIBC pool (BCG-treated / regimen-fit). Pembrolizumab + BCG is PRE-APPROVAL and ramps only from its estimated ~2028 launch; the gap below the lines is patients on BCG (or TURBT) alone with no novel add-on. All trajectories are stated assumptions in a pre-readout scenario, not reported figures.
Share of the 48k-patient addressable high-risk NMIBC pool this regimen is modelled to treat, by year
Keytruda is modelled at 0% of this pool in 2026, peaking at 12% in 2032; 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 (ImmunityBio) holds the largest rival share in 2026, 5% of the pool; that is the share Keytruda has to take or hold.
Rivals, rescaled - note the axis maximum (20%), 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.
Category timing: pembrolizumab BCG-unresponsive CIS monotherapy 2020; nadofaragene Dec 2022; N-803/Anktiva Apr 2024; TAR-200 and cretostimogene emerging. First-line BCG-combination pembrolizumab (KEYNOTE-676) modelled as an est. ~2028 US entry conditional on a positive readout. Shares reflect a crowded, delivery-diverse field and 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.
Estimated primary completion Jul 2026; pivotal Cohort A (CR rate) / Cohort B (EFS) data, the key de-risking event
Estimated US first approval (scenario, conditional on positive readout + filing)
IV pembrolizumab composition-of-matter LOE (~2028 US); subcutaneous pembrolizumab + biosimilars reshape franchise economics
✓ = 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 with BCG, high-risk NMIBC recurs in a majority of patients and a meaningful minority progress to muscle-invasive disease and cystectomy. The unmet need is durable, bladder-sparing disease control that reduces recurrence, progression and cystectomy, without the systemic toxicity of a checkpoint inhibitor in an early, organ-confined cancer. Whether pembrolizumab + BCG clears that bar (and how it compares with intravesical-delivery approaches like TAR-200 and N-803) is exactly what KEYNOTE-676 and its competitors are testing.
The synthesis for this indication, grounded in the cited trial, guideline and access facts above.
Rivals in this setting (High-risk NMIBC (BCG combination))
Swipe to explore →
| Rival / regimen | Developer | Position in this setting | Approved (date, trial, n) | Head start vs this regimen (months) | Source |
|---|---|---|---|---|---|
| TAR-200 (intravesical gemcitabine system) (Live threat) | Johnson & Johnson | Live threatwhyLeading rival, high CR rates and bladder-local delivery in BCG-naïve and BCG-unresponsive HR-NMIBC; a key efficacy/tolerability benchmark. | not in the record | not in the record | SunRISe (Johnson & Johnson) |
| N-803/Anktiva + BCG (Live threat) | ImmunityBio | Live threatwhyApproved (FDA Apr 2024) for BCG-unresponsive CIS (CR 62%); a BCG-combination rival expanding across HR-NMIBC. | Apr 2024, QUILT-3.032 | not in the record | QUILT-3.032 / FDA 2024 |
| Nadofaragene firadenovec (Adstiladrin) (Live threat) | Ferring | Live threatwhyApproved (FDA Dec 2022) for BCG-unresponsive CIS; established intravesical gene-therapy option. | Dec 2022, CS-003 | not in the record | Adstiladrin / FDA 2022 |
| Cretostimogene grenadenorepvec (Live threat) | CG Oncology | Live threatwhyAdvancing in high-risk NMIBC (BCG-unresponsive and BCG-naïve) with high CR rates; a fast-emerging rival. | not in the record | not in the record | BOND-003 / PIVOT-006 |
| Pembrolizumab monotherapy (KEYNOTE-057) (Merck & Co. pipeline) | Merck | Merck & Co. pipelinewhyKeytruda's OWN existing NMIBC label (BCG-unresponsive CIS, 2020, CR 41%); the beachhead KEYNOTE-676 expands from, not a competitor. | not in the record | not in the record | FDA approval of pembrolizumab for BCG-unresponsive NMIBC/CIS (KEYNOTE-057, Jan 2020) |
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 IV Q3W (Cohort A) or 400 mg IV Q6W (Cohort B) added to intravesical BCG, for a defined course (~1 year). Per-patient revenue is modelled from each market's published pembrolizumab per-dose net × the course. No indication-specific net price is disclosed; NMIBC uses the standard Keytruda molecule net.
Figures below are 2026 net prices, the basis the model is anchored on. The funnel applies -4%/yr from 2026, 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.
A ~1-year pembrolizumab course grosses ~$110k ASP in the US (≈17 Q3W doses at ~$11.8k, or ≈9 Q6W doses at ~$23.6k); realized exposure per treated patient is modelled at ~$150k US and lower ex-US on published tariffs (France ~$70k, Germany ~$78k AMNOG, Italy ~$62k, Spain ~$45k, UK ~$68k PAS, Japan ~$72k NHI, China ~$40k negotiated). −4%/yr forward. All figures are modelled: no KEYNOTE-676-specific net price is public, and the whole revenue line is a pre-approval scenario.
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 | Not approved (est. ~2028) | reference | None planned | BCG monotherapy | PRE-APPROVAL scenario. Readout est. Jul 2026 → filing → est. first approval ~2028 (conditional on positive Cohort A/B data). Pembrolizumab already approved for BCG-unresponsive CIS (2020). |
| EU | EMA / EC | Not approved (est. ~2029) | ~1 yr | None planned | BCG monotherapy | PRE-APPROVAL. EU filing would follow a positive readout; access est. ~2029, subject to CHMP + national HTA. |
| Japan | PMDA / NHI | Not approved (est. ~2029) | ~1 yr | None planned | BCG monotherapy | PRE-APPROVAL. Estimated access ~2029; NHI listing would follow. |
| China | NMPA | Not approved (est. ~2030) | ~2 yr | None planned | BCG monotherapy | PRE-APPROVAL. BCG supply and local practice patterns temper the addressable base; estimated access ~2030 if pursued. |
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 material move on this page, newest first, the public fact, and what our model made of it.
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.