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Keytruda (pembrolizumab) · anti-PD-1 · Merck & Co.
This page covers the 2L advanced-HCC indication only (KEYNOTE-224 + KEYNOTE-394, post-sorafenib/post-1L pembrolizumab monotherapy), not the 1L-NSCLC, perioperative, or other Keytruda settings, and not the 1L HCC IO-combo regimens. See all Keytruda indications →
SCOPE CORRECTION - the row's population description is stale. Current label 1.13: 'for the treatment of patients with hepatocellular carcinoma (HCC) SECONDARY TO HEPATITIS B who have received prior systemic therapy other than a PD-1/PD-L1-containing regimen.' The row's '2L hepatocellular carcinoma (post-sorafenib)' describes the ORIGINAL accelerated approval of 2018-11-09 on KEYNOTE-224. When that AA was converted to traditional approval on 2024-01-25 on the strength of KEYNOTE-394 - a trial conducted in Asian patients where HBV aetiology predominates - FDA rewrote the indication to HBV-related HCC and replaced the sorafenib-specific wording with any prior systemic therapy other than a checkpoint inhibitor. Both the aetiology restriction and the prior-therapy wording are materially different from the row. The trial pairing KEYNOTE-224/-394 is correct. No EU extension of indication on the EPAR as of 2026-09-16.
All markets
2026 net revenue · modelled 2L-HCC slice, WW 8-geo
$161M
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 is a Keytruda indication being squeezed from above and from behind at the same time. The 2L HCC pool shrinks every year that 1L IO combinations, atezolizumab plus bevacizumab from 2020, STRIDE from 2022, nivolumab plus ipilimumab from 2025, leave fewer patients IO-naive at second line, and then the ~2028 US pembrolizumab composition-of-matter expiry takes what is left. The curve reflects both: peak $171M in 2025, $79M by 2030, $46M by 2034. It is also an unusually geography-dependent label, because the Western confirmatory KEYNOTE-240 missed significance and the durable OS benefit rests on the Asian KEYNOTE-394 (HR 0.79), which matters commercially, since China holds the largest absolute pool and is exactly where cheaper NRDL-listed domestic PD-1s and camrelizumab plus rivoceranib take share. The honest read: modest single-agent activity at ~17% ORR, a defensible durable-responder tail, and a setting that is disappearing on schedule.
Threats land:1L IO adoption reaches near-universal in Western markets faster than modelled and the IO-naive 2L remainder collapses, while China's domestic PD-1 and IO-TKI combinations take the rest, so the line falls below the modelled $135M in 2028 before biosimilars are even the issue.
Modelled path:The 2L IO-naive pool keeps compressing on trend, pembrolizumab biosimilars arrive in the US ~2028 and EU ~2029, and the combined drag takes the line from $161M today to $79M in 2030 and a $46M tail.
Levers land:China's slower 1L IO shift keeps a structurally larger IO-naive 2L pool there than in the West, subcutaneous Keytruda Qlex defends administration share against IV biosimilars after 2028, and rising MASH-driven Western HCC incidence cushions the decline above the modelled $60M in 2031.
The fraction reaching second-line systemic therapy, roughly 13-18% of HCC patients, the digest names it as the softest input and it is stepped down from the HIMALAYA advanced fraction rather than measured. Stacked with the ~35-50% IO-naive share and China's ~55% access reach, these are Ormeval scoping estimates: Merck reports Keytruda as a $31.68B FY2025 franchise and never by indication or country.
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.
2L HCC is a modest, defensive slice of the Keytruda franchise rather than a major revenue line, its strategic value is breadth (another solid-tumour indication on the label) and the ASIAN 2L foothold won by KEYNOTE-394, not volume. It is structurally pressured from two sides: above, by 1L IO combinations (atezo+bev / IMbrave150, STRIDE / HIMALAYA, nivo+ipi / CheckMate 9DW) that compress the IO-naive 2L pool; and ahead, by the ~2028 pembrolizumab composition-of-matter LOE that exposes the whole franchise to biosimilars. China, the dominant HCC pool, is contested by cheaper domestic PD-1s and IO-TKI combos (camrelizumab+rivoceranib), capping branded penetration. The value lever is the durable-responder tail in the post-systemic-therapy setting, not market leadership.
Hepatocellular carcinoma, HBV-driven and Asia-concentrated (China ~half of global HCC), increasingly MASH/HCV-driven in the West, is usually diagnosed advanced. After progression on 1L therapy, pembrolizumab monotherapy is a 2L option: KEYNOTE-224 (ORR ~17%, FDA accelerated approval Nov 2018) and the confirmatory Asian KEYNOTE-394 Ph3 (OS HR 0.79; JCO 2023). It is a modest, China/Asia-weighted Keytruda line whose pool is structurally compressed as 1L IO combos (atezo+bev, STRIDE, nivo+ipi) push immunotherapy into the front line, shrinking the IO-naive 2L remainder. Exposed to the ~2028 pembrolizumab biologic LOE.
Hepatocellular carcinoma is >80% of primary liver cancer, a disease of chronic liver injury (hepatitis B in China, historically HCV in Japan, and rapidly-rising MASH/alcohol-related disease in the West). Liver cancer is markedly Asia-weighted: China alone is ~42% of global cases and roughly half of global HCC, Japan another high-incidence market, the West smaller but rising. HCC is usually diagnosed advanced and only a minority ever receives systemic therapy. The 2L setting is the subset who received 1L systemic therapy (historically sorafenib; increasingly a 1L IO combo) and progressed, are still Child-Pugh A and fit, and go on to a second line. Pembrolizumab monotherapy is one of the 2L options (alongside regorafenib, cabozantinib, ramucirumab and nivolumab). Critically, this 2L IO-naive pool SHRINKS as 1L IO combinations (atezolizumab+bevacizumab, durvalumab+tremelimumab, nivolumab+ipilimumab) become standard front-line, patients who already received IO in 1L are less likely to receive 2L pembrolizumab. Across the 8 modelled markets this is a small, China/Asia-weighted pool.
KEYNOTE-224 (single-arm Phase 2, Zhu/Lancet Oncology 2018) showed durable responses to pembrolizumab monotherapy in advanced HCC progressing on or intolerant to sorafenib (ORR ~17%, durable), driving the FDA ACCELERATED approval in November 2018. The confirmatory KEYNOTE-394 Phase 3 (Qin, JCO 2023), conducted predominantly in an ASIAN post-systemic-therapy HCC population, met its OS endpoint (HR 0.79), securing the 2L indication where the single-arm data alone could not. The companion KEYNOTE-240 Western Ph3 had earlier missed statistical significance on its co-primary endpoints, so the durable 2L label rests on the Asian KEYNOTE-394 win. This is a modest, Asia-weighted slice of the Keytruda franchise, and the 2L pool is compressed over time as 1L IO combinations move immunotherapy earlier.
2L sequencing depends on what was given in 1L: as 1L IO combos (atezo+bev, STRIDE, nivo+ipi) become standard, fewer patients are IO-naive at 2L, so 2L pembrolizumab is increasingly reserved for those whose 1L was a TKI (sorafenib/lenvatinib). The shrinking IO-naive 2L pool is the main forward funnel headwind. Child-Pugh A and adequate organ function are required.
KEYNOTE-224: single-arm, open-label Phase 2 (n=104) of pembrolizumab 200 mg q3w in advanced HCC previously treated with sorafenib; primary endpoint ORR (RECIST v1.1, blinded central review). KEYNOTE-394: randomized, double-blind Phase 3 (n=453) in a predominantly ASIAN post-systemic-therapy (post-sorafenib/oxaliplatin) advanced-HCC population, pembrolizumab + best supportive care vs placebo + BSC; primary endpoint OS. Both Child-Pugh A; all-comers (no PD-L1 selection); pembrolizumab continued until progression. The Western confirmatory KEYNOTE-240 (n=413) earlier missed statistical significance on its co-primary OS/PFS endpoints.
Load-bearing 6/7 sourced. ASSUMED uptake is yours to change.
This indication only, not Keytruda's total revenue
Second-line pembrolizumab monotherapy in advanced hepatocellular carcinoma after prior systemic therapy (sorafenib / 1L), Child-Pugh A, all-comers by PD-L1. KEYNOTE-224 (single-arm Ph2, post-sorafenib) supported the US accelerated approval; KEYNOTE-394 (randomized Ph3 in an Asian post-systemic-therapy population) confirmed the OS benefit. Pembrolizumab is dosed 200 mg q3w (or 400 mg q6w) until progression, the same molecule/dosing/pricing basis as the 1L-NSCLC Keytruda model.
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.
$161M
8 modelled markets (US, EU5, JP, CN) · modelled net revenue · 2026 (forecast)
Peak $171M · 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 (no indication × country actuals are reported) and calibrated to Merck's reported Keytruda franchise (FY2025 ≈ $31.68B), 2L HCC is a MODEST, China/Asia-weighted slice. The modelled 2L-HCC line ramps from the 2018 US accelerated approval, builds further on the 2023 Asian KEYNOTE-394 OS win, and plateaus around ~$0.6B across 2024–2026 before the combined drag of a SHRINKING 2L pool (1L IO combos move IO earlier) and the ~2028 biosimilar cliff pulls it down toward ~$0.2–0.3bn by the early 2030s. The 1L HCC market is dominated by atezolizumab+bevacizumab (IMbrave150) and durvalumab+tremelimumab (HIMALAYA); Keytruda's value here is the KEYNOTE-394-anchored ASIAN 2L foothold, not market leadership. 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 the 2L-reaching and IO-naive gates, plus a pembrolizumab share of ~27-34% of the IO-naive 2L pool outside China, with nets set modestly below the NSCLC model's; China is flagged as the biggest judgement call because it is the largest absolute pool and the one where the branded price and penetration assumptions are weakest.
The decline is defended, not certain
This decline is better defended than most because two independent mechanisms drive it, a pool that demonstrably shrinks as 1L IO becomes standard, and a dated composition-of-matter expiry at ~2028 US and ~2029 EU, so it does not depend on either alone. What is uncertain is the interaction: biologic erosion is gradual share loss rather than an overnight cliff, the SC Qlex conversion approved Sep 2025 is an explicit retention lever the model credits, and the mAb precedent of losing 40-60% of branded volume within twelve months would make the modelled glide from $135M in 2028 to $79M in 2030 too shallow.
What would change our mind
The base case is wrong if pembrolizumab biosimilars have not entered the US by end-2029, roughly half the remaining value is booked away between 2028 and 2031 on that date. It is wrong for a different reason if the IO-naive share of 2L HCC has already fallen below the modelled 35-50% in Western markets, since the pool gate, not the patent, is what determines whether the $151M booked for 2027 is real.
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 |
|---|---|---|---|---|---|---|---|---|---|---|
| Liver cancer incidence (2026) | 43k | 11k | 9.2k | 12k | 6.6k | 6.7k | 42k | 375k | 506k | GLOBOCAN 2022 |
New liver-cancer cases/yr (HCC is >80%); heavily Asia-weighted (HBV-driven). ~stable/rising (MASH). Shown for 2026: 2024 basis +1%/yr → ×1.020. Liver cancer is heavily Asia-weighted: China is ~42% of global cases (367.7k) and roughly half of global HCC (HBV-driven); Japan another high-incidence market (~41k); the West smaller but rising with MASH/HCV legacy. HCC is >80% of primary liver cancer. +1%/yr (MASH-driven rise). Identical incidence values to the HIMALAYA model for cross-consistency. | ||||||||||
| × HCCest | 82% | 80% | 80% | 80% | 80% | 80% | 90% | 85% | share, not summed | literature (>80%) |
Hepatocellular carcinoma (vs cholangiocarcinoma / other liver). HCC accounts for >80% of primary liver cancer; the share is higher in HBV-endemic Asia (China/Japan ~85–90%) and slightly lower in the West where cholangiocarcinoma is relatively more common. Matched to the HIMALAYA HCC fractions. | ||||||||||
| × Advanced & reaching 2L systemicest | 16% | 16% | 16% | 16% | 16% | 16% | 15% | 20% | share, not summed | modelled (1L→2L) |
Advanced HCC that received 1L systemic therapy (sorafenib/lenvatinib or a 1L IO combo), progressed, and is Child-Pugh A & fit for a SECOND line. Built off the HIMALAYA advanced-fraction logic but stepped DOWN to the 2L subset: most HCC is caught early (resection/transplant/ablation/TACE) or too late; of the advanced patients who reach 1L systemic therapy (~28–35%), roughly half remain Child-Pugh A and fit enough to receive a second line after progression, yielding ~15–20% of all HCC reaching 2L. Higher in China (later presentation, more 1L→2L flow), lower in Japan (intensive surveillance → earlier stage). The single biggest cross-market estimate, flagged. | ||||||||||
| × IO-naive at 2L (anti-PD-1-eligible)est | 40% | 40% | 40% | 40% | 40% | 40% | 45% | 55% | share, not summed | modelled (1L IO shift) |
2L patients who did NOT already receive immunotherapy in 1L, the shrinking pool eligible for 2L anti-PD-1. ERODES as 1L IO combos become standard. THE structural driver of this indication's decline. Pre-2020, almost all 2L patients were IO-naive (1L = sorafenib/lenvatinib TKI). As 1L IO combinations took over, the IO-naive share of the 2L pool fell, patients who got IO in 1L rarely receive 2L single-agent anti-PD-1. Modelled at a ~2024 mature level here (~0.40 West / ~0.55 China) and additionally captured in the pool trajectory's forward erosion; the steep Western 1L IO uptake makes the Western 2L IO-naive pool smaller than China's. Flagged estimated. | ||||||||||
| × 2L-systemic-treated & reachableest | 82% | 82% | 82% | 78% | 78% | 80% | 85% | 60% | share, not summed | access / 2L-treatment-rate |
Fit for and actually receiving a 2L systemic regimen (access/testing/oncology-reach). Branded pembrolizumab UPTAKE of this reachable pool is the share row below (excluded here to avoid double-counting). Captures the fraction of the IO-naive 2L pool that is fit for and actually reaches 2L systemic therapy (excludes those who decline to BSC, are unfit, or are untreated/unreached). High in Western academic systems and Japan (~0.78–0.85); lower in China (~0.60, oncology access concentrated in tier-1/2 cities, large rural under-treatment, though improved post-NRDL), broadly matching the 1L-NSCLC model's China reach. Excludes pembrolizumab UPTAKE, which is the competitive share layer below. | ||||||||||
| = Addressable 2L IO-naive HCC pool | 1.5k | 377 | 308 | 391 | 212 | 221 | 2.0k | 19k | 24k | computed |
Incidence × the rates above, advanced, Child-Pugh A HCC patients who reached 2L, are IO-naive, and are reachable for 2L anti-PD-1 therapy this year. Unlike the 1L pools, the 2L HCC IO-naive pool ERODES over the forecast: as 1L IO combinations (atezo+bev from 2020, STRIDE from 2022, nivo+ipi from 2025) become standard front-line, fewer 2L patients are IO-naive and eligible for 2L anti-PD-1. Western erosion is steeper (faster/earlier 1L IO uptake); Asia (esp. China, where TKI 1L lingered and 1L IO access is more gradual) erodes more slowly. Rising HCC incidence only partly offsets this. The forward trajectory therefore declines well before the ~2028 LOE, a genuinely shrinking addressable base. | ||||||||||
| × Keytruda uptake (branded) | 18% | 18% | 17% | 17% | 17% | 17% | 19% | 13% | 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 | 264 | 67 | 51 | 66 | 36 | 37 | 385 | 2.6k | 3.5k | computed · assumed input |
Addressable pool × branded uptake. | ||||||||||
| × Net price / patient (2026) | $168K | $85K | $88K | $80K | $75K | $83K | $69K | $27K | per patient, not summed | ASP · HTA · NRDL |
Same pembrolizumab molecule and dosing as the 1L-NSCLC model: 200 mg q3w (or 400 mg q6w) IV / SC Qlex until progression or a ~2-year cap, so per-patient revenue is the annual net cost while on-drug. US ASP ≈ $11.8k/200mg q3w (~$205k/yr list) net of ~10–15% physician-administered-biologic gross-to-net → ~$175k/yr net (set modestly below the NSCLC ~$180k to reflect shorter realized HCC course / poorer prognosis). EU nets ~$78–92k; Japan ~$72k (biennial NHI cuts); China ~$28k (NRDL/negotiated proxy, cheaper domestic PD-1 competition). −2%/yr forward erosion accelerating into LOE; held flat before 2024. ALL net prices are ESTIMATES, consistent with KEYTRUDA_1L_NSCLC_MODEL. 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 | $44.4M | $5.7M | $4.5M | $5.2M | $2.7M | $3.1M | $26.6M | $68.6M | $161M | 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, 2L systemic therapy in advanced HCC (IO-naive): 8 modelled markets (US, EU5, JP, CN)
Each agent's share of the addressable 2L IO-naive pool (advanced, Child-Pugh A HCC reaching 2L after 1L progression). The branded pembrolizumab line shows the post-2018 launch ramp, then the combined drag of a shrinking 2L pool and the ~2028 biosimilar erosion; the gap below the top line is patients on 2L TKIs, nivolumab, domestic PD-1s, or BSC. The branded pembrolizumab monotherapy line (IV + SC Qlex) is the only line this model monetizes.
Share of the 24k-patient addressable 2L IO-naive HCC pool this regimen is modelled to treat, by year
Keytruda is modelled at 14% of this pool in 2026, peaking at 14% in 2025; 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
Domestic PD-1 / IO-TKI (China) holds the largest rival share in 2026, 9% of the pool; that is the share Keytruda has to take or hold.
Rivals, rescaled - note the axis maximum (10%), 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 = market-by-market approval/reimbursement timing (US accelerated Nov 2018; ex-US 2019–20; China ~2022 post KN-394). 2L TKIs (regorafenib/cabozantinib/ramucirumab) and nivolumab take in-class share; domestic Chinese PD-1s take China-only share; pembrolizumab biosimilars timed to the ~2028 US / ~2029 EU LOE. Competitor trajectories are stated assumptions, not reported shares.
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.
Pembrolizumab composition-of-matter expiry (~2028); biosimilars erode the branded molecule across all indications, including 2L HCC
EU biosimilar entry; SC Qlex conversion partly defends administration share
Deeper 1L IO penetration (atezo+bev, STRIDE, nivo+ipi) continues to shrink the IO-naive 2L pembrolizumab pool
✓ = 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
Most 2L HCC patients progress quickly: pembrolizumab monotherapy ORR is ~17% (KEYNOTE-224), so the majority do not respond, and patients who already received a 1L IO combo derive little additional benefit from 2L single-agent anti-PD-1. There is no validated post-IO standard, liver decompensation (Child-Pugh B/C) removes many from any systemic option, and the 2L pool itself is shrinking as IO moves to 1L. That residual mortality and the post-IO gap keep the later-line HCC space contested (regorafenib, cabozantinib, ramucirumab, novel combinations) despite pembrolizumab's foothold.
The synthesis for this indication, grounded in the cited trial, guideline and access facts above.
Rivals in this setting (2L advanced HCC (post-sorafenib))
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| Rival / regimen | Developer | Position in this setting | Approved (date, trial, n) | Head start vs this regimen (months) | Failed endpoint | Source |
|---|---|---|---|---|---|---|
| Regorafenib (RESORCE) (Live threat) | Bayer | Live threatwhyApproved 2L after sorafenib (OS 10.6 vs 7.8 mo; HR 0.63), the established non-IO 2L backbone | not in the record | not in the record | - | RESORCE (2L, post-sorafenib) |
| Cabozantinib (CELESTIAL) (Live threat) | Exelixis / Ipsen | Live threatwhyApproved 2L/3L after prior systemic therapy (OS HR 0.76), a key non-IO competitor in the 2L slot | not in the record | not in the record | - | CELESTIAL (2L/3L) |
| Ramucirumab (REACH-2) (Watch) | Eli Lilly | WatchwhyApproved 2L for AFP-high HCC (OS HR 0.71), a biomarker-selected 2L option | not in the record | not in the record | - | REACH-2 (2L, AFP ≥400) |
| Nivolumab (CheckMate-040) (Live threat) | Bristol Myers Squibb | Live threatwhyThe other anti-PD-1 used in later-line HCC; CheckMate-459 1L missed OS significance, but nivolumab competes for the IO-naive 2L slot | not in the record | not in the record | 1L OS (CM-459) | CheckMate-040 |
| Camrelizumab + rivoceranib (CARES-310) (China rival) | Hengrui / Elevar | China rivalwhyChina-approved IO-TKI combo (OS HR 0.62), dominates the Chinese market and contests the 2L slot there | not in the record | not in the record | - | CARES-310 |
| Atezolizumab + bevacizumab (IMbrave150) (Pool erosion) | Roche / Genentech | Pool erosionwhyThe 1L LEADER (OS HR 0.58), not a direct 2L rival, but compresses the IO-naive 2L pool by moving IO to the front line | not in the record | not in the record | - | IMbrave150, atezolizumab + bevacizumab, 1L HCC (Finn, NEJM 2020) |
| Pembrolizumab biosimilars (Watch) | Generic (post-LOE) | WatchwhyUS composition-of-matter LOE ~2028; EU ~2029, erodes the branded molecule across all indications including 2L HCC | 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 the subcutaneous Qlex formulation (Sep 2025), continued until progression or 35 cycles (~2-year cap), so per-patient revenue is the annual net cost while on-drug. This is the SAME molecule/dosing/pricing as the 1L-NSCLC Keytruda model; net prices below are per-market, net of country discounts, set modestly below the NSCLC nets to reflect the shorter realized HCC course.
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 dosing and pricing here are identical in basis to the KEYTRUDA_1L_NSCLC_MODEL (same molecule): 200 mg q3w (or 400 mg q6w) IV / SC Qlex until progression or a ~2-year cap, so per-patient revenue is modelled as the annual net cost while on treatment. US ASP ≈ $11,795/200 mg q3w (~$205k/yr list) ⇒ ~$175k/yr net after ~10–15% physician-administered-biologic gross-to-net (set modestly below the NSCLC ~$180k to reflect the shorter realized 2L-HCC course and poorer prognosis). EU nets are HTA-negotiated (Germany ~$92k, France ~$88k, UK ~$86k, Italy ~$83k, Spain ~$78k); Japan NHI ~$72k (biennial cuts); China ~$28k (NRDL/negotiated proxy, cheaper domestic PD-1 competition). −2%/yr forward net erosion accelerating into LOE; 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 | 9 Nov 2018 (accelerated) | reference | None (all-comers) | Post-sorafenib (single-arm) | Accelerated approval on KEYNOTE-224 ORR; Medicare Part B (J9271); ~10–15% gross-to-net on a physician-administered biologic. Confirmed by KEYNOTE-394 OS (2023) |
| Japan | PMDA / NHI | ~2019–20 | ~1 yr | None | Post-systemic-therapy | High-incidence HCC market; NHI-listed; biennial NHI price cuts. Asian 2L data (KN-394) most relevant here |
| Germany | G-BA / IQWiG | ~2019 | ~0.6 yr | None | BSC / 2L TKI | AMNOG net below list; reimbursed but a small later-line HCC pool |
| France | HAS | ~2019–20 | ~0.8 yr | None | BSC / 2L TKI | ATU/reimbursement; SMR/ASMR modest for a later-line monotherapy |
| Italy | AIFA | ~2020 | ~1.5 yr | None | BSC / 2L TKI | Class H; managed entry + regional formulary lag; high HCV-legacy HCC burden |
| Spain | SEFH / MoH | ~2020 | ~2 yr | None | BSC / 2L TKI | Financed later-line; +17-region formulary lag; lowest Western net |
| UK | NICE | ~2020–21 | ~1.5 yr | None | BSC / 2L TKI | Confidential PAS; later-line HCC pool small |
| China | NMPA / NRDL | ~2022 (post KN-394) | ~1 yr | None | 2L TKI / domestic PD-1 | Asian KEYNOTE-394 data support 2L use; competes with cheaper NRDL-listed domestic PD-1s and IO-TKI combos, branded penetration capped, net price low |
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.