{"documentId":"1H3NICESubmissionPlanVeltarix_vwx109XyZ123AbCdEfGh","title":"NICE STA Submission Plan — Veltarix","revisionId":"rev-1H3NICESubmi","body":{"content":[{"sectionBreak":{"sectionStyle":{"columnSeparatorStyle":"NONE","contentDirection":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":72,"textRun":{"content":"NICE Single Technology Appraisal — Veltarix for NSCLC. Submission Plan\n","textStyle":{"bold":true}}}],"paragraphStyle":{"namedStyleType":"TITLE","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":167,"textRun":{"content":"Prepared by Sara Lindqvist, HEOR Director (UK HTA Lead). Distribution: VP Commercial, Global Value & Access, Clinical Development, External Assessment Group liaison.\n","textStyle":{}}}],"paragraphStyle":{"namedStyleType":"NORMAL_TEXT","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":10,"textRun":{"content":"Overview\n","textStyle":{"bold":true}}}],"paragraphStyle":{"namedStyleType":"HEADING_2","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":389,"textRun":{"content":"Veltarix is the EU brand name for the molecule sold as Zenvara in the United States. The chemical entity, indication, and clinical evidence are identical; only the brand, pack, and regional pricing differ. This submission is to NICE under the Single Technology Appraisal (STA) process per PMG24 for the indication of first-line treatment of metastatic NSCLC in patients with PD-L1 ≥ 50%.\n","textStyle":{}}}],"paragraphStyle":{"namedStyleType":"NORMAL_TEXT","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":330,"textRun":{"content":"Reference number: GID-TA11218 (in development). NICE process anchor dates: scoping completed 2026-04-02; company submission deadline 2026-09-01; External Assessment Group engagement 2026-06-15; first committee meeting 2026-10-14; second committee meeting (if required) 2026-12-02; expected final guidance publication 2026-12-23.\n","textStyle":{}}}],"paragraphStyle":{"namedStyleType":"NORMAL_TEXT","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":347,"textRun":{"content":"ICER threshold strategy: assume £28,000 per QALY base case, well within the NICE standard range of £20,000-£30,000 per QALY. End-of-life modifier applied (Veltarix qualifies as 24-month median life extension in indicated population is met). Patient Access Scheme (PAS) under legal review; expected approval mid-July to support submission timing.\n","textStyle":{}}}],"paragraphStyle":{"namedStyleType":"NORMAL_TEXT","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":41,"textRun":{"content":"Decision problem (per final NICE scope)\n","textStyle":{"bold":true}}}],"paragraphStyle":{"namedStyleType":"HEADING_2","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":137,"textRun":{"content":"Population: Adults with metastatic NSCLC, PD-L1 TPS ≥ 50%, no prior systemic therapy. Approximately 4,200 patients per year in England.\n","textStyle":{}}}],"paragraphStyle":{"namedStyleType":"NORMAL_TEXT","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":61,"textRun":{"content":"Intervention: Veltarix monotherapy, 480mg IV every 6 weeks.\n","textStyle":{}}}],"paragraphStyle":{"namedStyleType":"NORMAL_TEXT","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":97,"textRun":{"content":"Comparators (per NICE scope): (1) pembrolizumab monotherapy; (2) platinum doublet chemotherapy.\n","textStyle":{}}}],"paragraphStyle":{"namedStyleType":"NORMAL_TEXT","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":183,"textRun":{"content":"Outcomes: Overall survival, progression-free survival, response rate, health-related quality of life (using EQ-5D-5L), adverse events grade 3+, treatment discontinuation due to AEs.\n","textStyle":{}}}],"paragraphStyle":{"namedStyleType":"NORMAL_TEXT","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":15,"textRun":{"content":"Module status\n","textStyle":{"bold":true}}}],"paragraphStyle":{"namedStyleType":"HEADING_2","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":123,"textRun":{"content":"Module A (Decision problem and description of technology): Complete. Reviewed by VP Commercial and signed off 2026-04-30.\n","textStyle":{}}}],"paragraphStyle":{"namedStyleType":"NORMAL_TEXT","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":294,"textRun":{"content":"Module B (Clinical effectiveness): In review. Systematic literature review (SLR) complete; ITC vs platinum doublet methodology finalized in March 2026. Awaiting final IPD-level ZENITH-1 5-year update for inclusion (ASCO 2026 presentation embargoed until June 2). Expected complete by July 15.\n","textStyle":{}}}],"paragraphStyle":{"namedStyleType":"NORMAL_TEXT","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":350,"textRun":{"content":"Module C (Cost-effectiveness model): Tech engagement with EAG scheduled June 8. The economic model is a 4-state partitioned-survival model with progression-free, post-progression, and death states. Extrapolation method: parametric (Weibull) for PFS, log-logistic for OS. Time horizon: 30 years (lifetime). Discount rate: 3.5% per UK reference case.\n","textStyle":{}}}],"paragraphStyle":{"namedStyleType":"NORMAL_TEXT","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":256,"textRun":{"content":"Module D (Budget impact analysis): In progress. 5-year BIA for NHS England. Eligible population estimated at 4,200 patients per year; current standard of care assumption uses 78% pembrolizumab / 22% platinum doublet split based on Cancer Drugs Fund data.\n","textStyle":{}}}],"paragraphStyle":{"namedStyleType":"NORMAL_TEXT","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":191,"textRun":{"content":"Patient Access Scheme: Under legal review. Expected approval mid-July. Discount structure confidential; will be filed as confidential commercial information per NICE PAS submission process.\n","textStyle":{}}}],"paragraphStyle":{"namedStyleType":"NORMAL_TEXT","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":224,"textRun":{"content":"External Assessment Group report: independent. EAG appointed by NICE 2026-04-15 (BMJ Technology Assessment Group, University of York). EAG critique expected approximately 8 weeks after company submission (~early November).\n","textStyle":{}}}],"paragraphStyle":{"namedStyleType":"NORMAL_TEXT","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":26,"textRun":{"content":"Decision problem details\n","textStyle":{"bold":true}}}],"paragraphStyle":{"namedStyleType":"HEADING_2","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":357,"textRun":{"content":"Why pembrolizumab and platinum doublet as comparators: pembrolizumab monotherapy is the current standard for PD-L1 ≥ 50% per NICE TA683. Platinum doublet remains relevant for patients ineligible for or intolerant to immunotherapy. NICE scope does not include atezolizumab or cemiplimab as primary comparators despite both being licensed in the indication.\n","textStyle":{}}}],"paragraphStyle":{"namedStyleType":"NORMAL_TEXT","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":400,"textRun":{"content":"Why NICE end-of-life criteria are met: Indication has median life expectancy < 24 months on standard of care (current 19.4 months from ZENITH-1 control arm). Veltarix extends life by > 3 months (median 24.7 vs 19.4, delta 5.3 months). Veltarix is licensed for a population of approximately 4,200 patients per year in England — below the 7,000-patient threshold for end-of-life modifier eligibility.\n","textStyle":{}}}],"paragraphStyle":{"namedStyleType":"NORMAL_TEXT","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":24,"textRun":{"content":"Economic model summary\n","textStyle":{"bold":true}}}],"paragraphStyle":{"namedStyleType":"HEADING_2","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":150,"textRun":{"content":"Manufacturer base-case ICER: £24,800 per QALY vs pembrolizumab; £19,200 per QALY vs platinum doublet. Both within the £20k-£30k NICE standard range.\n","textStyle":{}}}],"paragraphStyle":{"namedStyleType":"NORMAL_TEXT","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":306,"textRun":{"content":"Key driver of ICER: long-term OS extrapolation beyond trial follow-up. The trial provides direct evidence to month 48; from month 48 to month 360 (lifetime horizon) is extrapolated. The base-case uses log-logistic extrapolation; sensitivity analyses use Weibull, Gompertz, and a constant-mortality model.\n","textStyle":{}}}],"paragraphStyle":{"namedStyleType":"NORMAL_TEXT","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":155,"textRun":{"content":"PSA results: 78% probability cost-effective at £30,000/QALY versus pembrolizumab; 91% probability cost-effective at £30,000/QALY versus platinum doublet.\n","textStyle":{}}}],"paragraphStyle":{"namedStyleType":"NORMAL_TEXT","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":139,"textRun":{"content":"Patient Access Scheme: confidential discount applied to net price; PAS reduces base-case ICER by an additional approximately £4,800/QALY.\n","textStyle":{}}}],"paragraphStyle":{"namedStyleType":"NORMAL_TEXT","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":45,"textRun":{"content":"Outstanding gaps (4 blocker gaps remaining)\n","textStyle":{"bold":true}}}],"paragraphStyle":{"namedStyleType":"HEADING_2","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":496,"textRun":{"content":"Gap 1 (BLOCKER) — Long-term OS durability extrapolation. The trial follow-up is 48 months; the model extrapolates to 360 months. The EAG is likely to challenge the log-logistic extrapolation method. Mitigation: include sensitivity analyses with three alternative extrapolation methods, plus real-world evidence from the ZEN-RWD registry (interim analysis available Q3 2026). Estimated months to close: 14 months (real-world data maturity is the rate-limiting step). Owner: Clinical Development.\n","textStyle":{}}}],"paragraphStyle":{"namedStyleType":"NORMAL_TEXT","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":456,"textRun":{"content":"Gap 2 (BLOCKER) — Indirect treatment comparison vs platinum doublet. ZENITH-1 did not include a platinum doublet arm; ITC is via network meta-analysis using KEYNOTE-189 and KEYNOTE-024 historic controls. Methodological challenge: heterogeneity in PD-L1 testing across constituent trials. Mitigation: include three NMA methodological variants in the submission, document heterogeneity exhaustively. Estimated months to close: 3 months (June). Owner: HEOR.\n","textStyle":{}}}],"paragraphStyle":{"namedStyleType":"NORMAL_TEXT","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":283,"textRun":{"content":"Gap 3 (BLOCKER) — Subgroup analyses for restricted PD-L1 expression definitions. NICE may request analyses on TPS 50-79% vs TPS 80%+ separately. Mitigation: pre-prepare subgroup analyses for both definitions, include in submission. Estimated months to close: 6 months. Owner: HEOR.\n","textStyle":{}}}],"paragraphStyle":{"namedStyleType":"NORMAL_TEXT","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":308,"textRun":{"content":"Gap 4 (BLOCKER) — Patient and public involvement consultation. NICE requires patient organization submissions. Mitigation: confirmed engagement with Roy Castle Lung Cancer Foundation (UK), Lung Cancer Europe. Submissions due to NICE 2026-08-15. Estimated months to close: 4 months. Owner: Patient Advocacy.\n","textStyle":{}}}],"paragraphStyle":{"namedStyleType":"NORMAL_TEXT","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":46,"textRun":{"content":"Gaps with manageable risk (4 major, 3 minor)\n","textStyle":{"bold":true}}}],"paragraphStyle":{"namedStyleType":"HEADING_2","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":255,"textRun":{"content":"Major: Real-world utility data for the post-progression health state. Major: ITC sensitivity to PD-L1 testing methodology assumptions. Major: Treatment-discontinuation modeling in the post-progression state. Major: HRQoL data collection beyond month 36.\n","textStyle":{}}}],"paragraphStyle":{"namedStyleType":"NORMAL_TEXT","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":140,"textRun":{"content":"Minor: Disease management cost data updates. Minor: Drug acquisition cost confirmation post-PAS. Minor: Comparator price-erosion modeling.\n","textStyle":{}}}],"paragraphStyle":{"namedStyleType":"NORMAL_TEXT","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":7,"textRun":{"content":"Risks\n","textStyle":{"bold":true}}}],"paragraphStyle":{"namedStyleType":"HEADING_2","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":139,"textRun":{"content":"EAG critique of extrapolation method: HIGH probability of formal challenge. Mitigation: pre-engagement at tech engagement meeting June 8.\n","textStyle":{}}}],"paragraphStyle":{"namedStyleType":"NORMAL_TEXT","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":129,"textRun":{"content":"EAG critique of ITC methodology: MEDIUM probability. Mitigation: comprehensive sensitivity analyses, transparent documentation.\n","textStyle":{}}}],"paragraphStyle":{"namedStyleType":"NORMAL_TEXT","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":130,"textRun":{"content":"Patient organization submission timing: LOW probability of delay. Mitigation: established relationships with both organizations.\n","textStyle":{}}}],"paragraphStyle":{"namedStyleType":"NORMAL_TEXT","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":117,"textRun":{"content":"PAS approval timing: LOW probability of slippage. Mitigation: legal review is on track per current weekly check-in.\n","textStyle":{}}}],"paragraphStyle":{"namedStyleType":"NORMAL_TEXT","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":18,"textRun":{"content":"Cross-references\n","textStyle":{"bold":true}}}],"paragraphStyle":{"namedStyleType":"HEADING_2","direction":"LEFT_TO_RIGHT"}}},{"paragraph":{"elements":[{"startIndex":1,"endIndex":145,"textRun":{"content":"Evidence Dossier Index (1I8…), HTA Evidence Gap Report Q2 2026 (1J4…), 2024 G-BA Dossier Lessons Learned (1K7…), Zenvara US Launch Plan (1V3…).\n","textStyle":{}}}],"paragraphStyle":{"namedStyleType":"NORMAL_TEXT","direction":"LEFT_TO_RIGHT"}}}]},"documentStyle":{"pageNumberStart":1,"marginTop":{"magnitude":72,"unit":"PT"},"marginBottom":{"magnitude":72,"unit":"PT"},"marginLeft":{"magnitude":72,"unit":"PT"},"marginRight":{"magnitude":72,"unit":"PT"},"pageSize":{"height":{"magnitude":792,"unit":"PT"},"width":{"magnitude":612,"unit":"PT"}}},"namedStyles":{"styles":[{"namedStyleType":"NORMAL_TEXT","textStyle":{"fontSize":{"magnitude":11,"unit":"PT"}}},{"namedStyleType":"TITLE","textStyle":{"fontSize":{"magnitude":26,"unit":"PT"},"bold":true}},{"namedStyleType":"HEADING_1","textStyle":{"fontSize":{"magnitude":20,"unit":"PT"},"bold":true}},{"namedStyleType":"HEADING_2","textStyle":{"fontSize":{"magnitude":16,"unit":"PT"},"bold":true}}]},"lists":{},"inlineObjects":{},"headers":{},"footers":{},"footnotes":{},"suggestionsViewMode":"DEFAULT_FOR_CURRENT_ACCESS"}