Intro: When “positive” data isn’t enough for price
Teams celebrate a Phase 3 readout: primary endpoint met, safety clean, filing on track. But the mood changes once pricing and HTA teams start modelling. The comparator used in the pivotal trial doesn’t align with real-world standard of care in major markets.
Suddenly the asset struggles to show incremental value. HTAs downgrade the evidence. Payers push for deep discounts. A program that looked “de-risked” hits a commercial wall.
This is more common than people admit—especially in global programs trying to reconcile FDA expectations with EU access realities.
Why this happens in real life
- Global trial design anchored to FDA norms, not EU HTA evidence needs.
- Emerging competitor enters as new standard of care during the long Phase 3 execution window.
- Protocol locked before payer input or landscape simulation was performed.
- Bridging studies dismissed as “nice to have” due to budget or timeline pressure.
- Internal teams underestimate how aggressively some HTAs benchmark against real-world treatment patterns.
Commercial & deal impact
- Price corridor drops 20–40% vs. initial business case assumptions.
- Payer negotiations drag 6–12 months due to weak comparative effect size.
- Partnering discussions stall or shift to lower upfront/milestones.
- Access delayed in EU5, disproportionately affecting first-year revenue curves.
- NPV compression forces reprioritization of label expansion or lifecycle investments.
How strong teams handle it
- Run a payer-derived “evidence acceptability” review before finalizing Phase 3 comparator.
- Use HTA simulation models to test price elasticity under different comparator assumptions.
- Pre-plan indirect treatment comparisons (ITCs) with robust methodology, not as an afterthought.
- Establish a governance gate: trial design cannot lock without cross-functional sign-off (regulatory + MAx + HEOR).
- Monitor live competitor uptake during the trial and prepare contingency evidence packages.
- Budget small, rapid real-world evidence studies to bridge gaps pre-HTA submission.
Why this matters for BD & strategy
- Comparator risk is one of the biggest hidden drivers of value erosion in late-stage assets.
- BD teams must discount projections if pivotal evidence is misaligned with payer expectations.
- Portfolio strategy should flag therapeutic areas where standards of care shift rapidly.
- Ignoring comparator dynamics leads to poor deal timing, mispriced assets, and avoidable post-deal tensions.