Most Value-Added Medicines don't fail in the lab. They fail at the point where a regulator, an HTA body or a payer has to decide what the improvement is actually worth.
A Value-Added Medicine (VAM)starts from a molecule that is already known, already approved, already trusted — and builds new value around it: a better formulation, a new route of administration, a smarter device, a repositioned indication. The science is often the easier part. The harder part is proving, market by market, that, based on the evidence available, the incremental benefit deserves to be recognised and paid for.
That gap between the perceived (and demonstrated) value created and the value recognised is where most VAM strategies succeed or stall.
Five routes to additional value add for a known molecule
Incremental innovation isn't one thing. It takes several recognisable forms, each with its own evidence requirements and its own value recognition.
| Archetype | What it does | Example |
| Repurposing | A known molecule in a new therapeutic indication | Low-dose colchicine, repurposed for coronary artery disease |
| Reformulation | A new formulation, salt or extended-release profile of the same active | Liposomal doxorubicin, reducing cardiotoxicity |
| Fixed-dose combination | Two or more approved actives combined into one unit | Sacubitril/valsartan, combining an off-patent ARB with a new agent |
| Route of administration | A new way of delivering the same active | Subcutaneous trastuzumab, replacing IV infusion |
| Device differentiation | A new delivery device around an established product | Self-dose injector pens replacing prefilled syringes |
Each type of incremental value faces different burden of proof, and a different payer reaction, as the next sections show. A sixth case sits outside this list: Rx-to-OTC switches (naproxen in the UK, for example) take a product out of standard reimbursement negotiations altogether, so value is captured through out-of-pocket purchasing and brand loyalty rather than payer pricing.
The Recognition Gap
HTA frameworks assess demonstrated benefit over existing treatments, rather than novelty of mechanism of action, but may not fully capture the broader value of improvements to established medicines. This mismatch is often called the Recognition Gap: the challenge of translating clinical, economic and organisational benefits into evidence that actually moves a pricing or reimbursement decision.
The lesson isn't that the evidence was weak. It's that evidence alone doesn't close the Recognition Gap — the pricing case has to be built alongside it, market by market, from early in development and from a payer perspective.
Five markets, five different answers
Europe has no single VAM pathway. France, Germany, Italy, Spain and the UK each decide differently whether incremental value counts — and what it takes to prove it.
| Market | Who decides | Does convenience count? | What actually wins |
| France | HAS assesses, CEPS prices | Only once converted into a clinical outcome | Robust clinical endpoints, designed in prospectively, plus care-pathway evidence (HAS Section 8) where relevant |
| Germany | G-BA decides, GKV-SV prices | Only as therapeutic improvement under §35 SGB V | Morbidity outcomes vs. the G-BA comparator, in defined subgroups |
| Italy | AIFA — one merged scientific and economic commission | Yes, explicitly — including PROMs and PREMs | A full economic portfolio (budget impact, cost-effectiveness, cost-utility) plus registry data |
| Spain | Ministry of Health + CIPM, then 17 regions | Only if quantified as compliance or resource saving | Budget impact plus a regional resource case, made 17 times over |
| UK | NICE/SMC, then Integrated Care Boards locally | Yes — if it is cash-releasing | Operational cost-offsets a finance director can actually bank |
In France, around half of important products rated ASMR V (the lowest clinical-improvement rating) in 2025 went unrewarded for their incremental value. In Spain, post-approval uptake is decided independently across 17 autonomous communities, and in 2025 just over half of medicines faced restrictions somewhere in the country.
The practical consequence: a dossier built for one market rarely travels to the next. Evidence and pricing strategy have to be designed market by market, from the outset — not adapted after the fact.
Article 84: a new incentive, with limits
Adopted in December 2025 and expected to apply from around 2028, Article 84 gives Europe something it didn't have before: a defined regulatory pathway that rewards repurposing research, broadly analogous to the US 505(b)(2) route. It grants four years of data protection — but only on the new-indication data, not on the active substance itself. For now, it covers repurposing specifically; the European Commission has signalled it may extend to reformulation and new routes of administration later.
Article 84 sits alongside the existing EU pathways (Article 8 full dossiers, the Article 10 family for generic, bibliographic and fixed-dose-combination routes, and the PUMA route for paediatric use) rather than replacing any of them.
The strategic implication is the one that matters most: a regulatory reward doesn't automatically become a pricing reward. The PUMA pathway is a cautionary tale: pricing outcomes for approved PUMA products have been inconsistent, and a regulatory premium has not always survived contact with payers. The sponsors who get the most out of Article 84 will be the ones who engage HTA bodies early, from the CMC stage, and build their evidence generation strategy around the eventual pricing case, not just the regulatory dossier.
How PLG supports sponsors, end to end
PLG works alongside pharmaceutical companies throughout the Value-Added Medicines journey, organised as one cross-functional programme in which regulatory, HTA and evidence timelines are aligned from the start, rather than a different vendor at every stage. Four business units contribute:
- Product Development & Engineering: build value in by design. Clinical strategy and study design around payer-recognised endpoints, clinical pharmacology, CMC and galenic development, and regulatory strategy across the Article 10, PUMA and Article 84 routes.
- Market & Patient Access: turn value into price. Market access and pricing strategy, HTA and P&R submissions, and health-economic models anchored to cost-offsets payers can bank.
- Digital & Innovation: make soft outcomes hard. Validated PROMs and PREMs and digital patient-support programmes that turn adherence, persistence and experience into HTA-relevant data.
- Product Compliance: keep value live. Registrations, regulatory operations, safety and quality, so that authorisations stay active and synchronised across markets.
The result is one value story, adapted market by market: regulatory, clinical, HTA and market access expertise under one roof, with dialogue opened with HTA bodies before submission rather than after.
Talk to our experts
Whether you're assessing whether a known molecule deserves a new indication, a new formulation or a new route of administration — or trying to understand how that value will actually be assessed across France, Germany, Italy, Spain and the UK — our market access and regulatory experts can help you build the case from the start, not retrofit it later.
