Presentation (CTI)

OBJECTIVES: Personalized cancer vaccines (PCVs) utilize advanced artificial intelligence (AI) algorithms to design custom, patient-specific neoantigen immunotherapies. Operating as a dynamic "N-of-1" platform rather than a static compound, PCVs introduce unprecedented structural risks to traditional clinical development and market access pathways. With Phase 3 results for leading PCV programs anticipated within 2-3 years, biopharma faces an urgent strategic uncertainty whether the value of PCV will be recognized.
METHODS: A structured desk research review was conducted to identify characteristics of PCVs that are fundamentally incompatible with existing regulatory and HTA frameworks, and to define strategic mitigations for market access teams ahead of pivotal trial completion.
RESULTS: Regulatory and HTA incompatibilities were identified. Traditional Chemistry, Manufacturing, and Control frameworks cannot accommodate patient-specific lots, as standardised batch-release potency assays are inapplicable to individually manufactured products. Furthermore, the self-learning AI neoantigen selection algorithm creates a regulatory paradox, forcing platform-based assessment and iterative reevaluation as the algorithm evolves. HTA bodies lack methodology to appraise platform-based therapies where no two products are identical, fundamentally undermining population-level comparative evidence standards. The 4-to-8-week manufacturing turnaround introduces a pre-treatment lag that may exclude progressing patients from per-protocol populations, diluting observed treatment effects in intention-to-treat analyses. Finally, inter-patient variability in neoantigen profiles cannot be balanced through randomisation, limiting trial generalisability and complicating cost-effectiveness modelling. The absence of validated predictive biomarkers compounds these challenges by precluding the preselection of likely responders.
CONCLUSIONS: These incompatibilities cannot be resolved through conventional market access strategies. Moreover, with the EU HTA Regulation now mandating Joint Clinical Assessments (JCA) for all new oncology and ATMP products from January 2025, developers must proactively define JCA-suitable evidence packs. Recommended strategic actions include platform-level regulatory and HTA assessment supported with cross-indication immune response data aggregation, pre-specified immunologically driven biomarker patient stratification, and outcome-based reimbursement agreements incorporating long-term registries to support iterative reassessment.