📁Pharma Team / Shared drive

Across the global submission portfolio (NICE, G-BA, HAS, CADTH, JCA), three blocker-severity gaps remain at Q2 2026. The combined estimated time to close all three is approximately 18 months, with the long-term durability extrapolation being the rate-limiting step. None of the blocker gaps prevents the NICE submission from filing in September 2026; all three are expected to be raised by the External Assessment Group and our response is being prepared in parallel.

Blocker gaps

Gap 1 — Indirect Treatment Comparison vs Platinum Doublet Chemotherapy. ZENITH-1 did not include a platinum doublet arm. The ITC is required by NICE (Module B), G-BA (Module 4 patient-relevant endpoints), CADTH (clinical evidence section), and JCA. Methodology challenge: heterogeneity in PD-L1 testing across constituent trials (KEYNOTE-189, KEYNOTE-024, IMpower-130). Three NMA methodological variants prepared (Bucher, Bayesian, ITC with adjustment for PD-L1 cut-off). Estimated months to close: 3 (target June 2026). Owner: HEOR.

Gap 2 — Long-term OS Durability Extrapolation. Trial follow-up is 48 months; the economic model requires extrapolation to 360 months (30-year horizon) for the NICE reference case. Four alternative parametric extrapolation methods are tested in PSA; the differences in ICER are within ±£8,000/QALY between methods. Critical evidence to support choice: ZEN-RWD real-world registry interim analysis. Estimated months to close: 14 (target Q3 2027). Owner: Clinical Development.

Gap 3 — Subgroup analysis for renal-impaired patients (eGFR < 60). G-BA has specifically requested subgroup analysis in this patient population. ZENITH-1 enrolled patients with eGFR ≥ 50 mL/min; the subgroup of eGFR 50-60 is small (n=42). Power for the subgroup analysis is limited. Estimated months to close: 6 (target Q4 2026, contingent on pooled analysis with IMpact-2 data). Owner: Clinical Development + HEOR.

Major-severity gaps

Real-world utility data for the post-progression health state. Source: ZEN-RWD registry, target Q3 2026.

Treatment-discontinuation modeling in the post-progression state. Source: literature + ZEN-RWD, target Q4 2026.

HRQoL data collection beyond month 36. Source: ZEN-RWD, target Q3 2026.

Comparator price-erosion modeling (post-pembrolizumab biosimilar entry forecast). Source: external market intelligence, target Q3 2026.

Minor-severity gaps

Disease management cost data updates (UK PSSRU 2026, Germany EBM 2026, France ATIH 2026). Source: standard health-economic data sources, target Q3 2026.

Drug acquisition cost confirmation post-PAS in UK. Source: contracting team, target on PAS approval.

Patient organization engagement evidence (Italy, Spain — preparing for HAS and JCA submissions). Source: medical communications, target Q4 2026.

Gap close trajectory

Q3 2026: ITC vs platinum doublet (blocker) closed. ZEN-RWD interim analysis published (closes 4 major gaps).

Q4 2026: Renal subgroup analysis published (closes blocker 3). Comparator price erosion modeling complete.

Q1 2027: HAS submission filed. CADTH submission filed.

Q3 2027: ZEN-RWD long-term durability analysis sufficient to close blocker 1 (long-term extrapolation).

Q4 2027: All Q2 2026 blocker gaps closed. Portfolio in steady state through 2028 indication-expansion cycle.

Risks

ZEN-RWD enrollment lag: current enrollment 1,840 vs target 4,000 by Q4 2026. If enrollment continues at current pace (220 patients per quarter), target is achievable. Risk: a 25% enrollment slowdown would push the durability gap close from Q3 2027 to Q1 2028, with knock-on effect on G-BA reassessment cycle.

EAG critique severity: low to medium probability that the EAG raises issues beyond the prepared responses. Mitigation: tech engagement meeting June 8 will allow early triangulation.

JCA scoping changes: JCA PICOs are still being consolidated. If late-stage member-state submissions introduce new PICO requirements, evidence gaps could expand.

Cross-references

Evidence Dossier Index (1I8…), NICE STA Submission Plan (1H3…), 2024 G-BA Dossier Lessons Learned (1K7…).