From Early Access to Reimbursement: Exploring Price Differences in France

France’s early access (Accès Précoce) program allows patients with serious, rare, or disabling diseases to access promising medicines before they enter the standard reimbursement pathway. However, certain eligibility requirements must be met: no appropriate treatment is available, treatment initiation cannot be delayed, and the medicine must be presumed innovative, with efficacy and safety strongly presumed.

For pharmaceutical companies, this program creates a distinctive pricing situation. During early access, manufacturers can freely set a maximum compensation price (indemnité maximale) before the price is negotiated with the French Economic Committee for Health Products (CEPS) for standard reimbursement (i.e., the conventional reimbursement pathway in France).

But what happens to that price when a medicine transitions to standard reimbursement?

We analyzed 34 medicines and found that standard reimbursement list prices were on average 14.5% lower than early access compensation prices. However, individual differences ranged widely, from a 73.1% decrease to an 11.2% increase.

Here, we discuss several emerging trends associated with smaller or greater price decreases and how manufacturers can better align their early access compensation strategy from the outset.

What did we analyze?

Using publicly available data, we identified medicines granted early access since the French early access scheme was reformed in July 2021.

Maximum early access compensation prices were obtained from French Ministry of Health data, while ex-factory list prices (prix fabricant hors taxe, PFHT) at standard reimbursement were retrieved from the French Official Journal. Throughout this article, “reimbursement price” refers to the ex-factory list price. It does not account for confidential rebates or contractual arrangements that may affect the actual net price negotiated between manufacturers and the CEPS.

Our analysis focused on first reimbursement listings and included only medicines for which early access was granted before publication of the reimbursement price. Early access applications for indication extensions were excluded.

Overall, 34 medicines were included.

Importantly, this was a purely descriptive analysis. No formal statistical analysis was performed to test associations between individual factors and price differences. The results should therefore be interpreted as trends observed within our sample rather than as evidence of causal relationships or predictors of future pricing outcomes.

Early access prices are generally higher, but the gap varies considerably

Across the 34 medicines analyzed, the average difference between the early access compensation price and the standard reimbursement list price was -14.5%, with a median difference of -10.9%.

More importantly, the magnitude of the difference varied substantially between products, ranging from -73.1% to +11.2%.

This variability suggests that there is no uniform relationship between the compensation price selected during early access and the list price ultimately obtained at standard reimbursement.

We therefore explored several characteristics of the subsequent HTA assessment to identify potential trends that could help understand these differences.

Clinical value and therapeutic positioning appear to matter

Two components of the French HTA assessment are particularly relevant to understanding these results:

1. The Clinical Value (Service Médical Rendu, SMR), which assesses the clinical benefit of a medicine and informs the reimbursement decision
2. The Added Clinical Value (Amélioration du Service Médical Rendu, ASMR), which assesses its added clinical benefit compared with existing alternatives and is an important consideration in price negotiations

In our sample, most medicines received an important SMR. Only two received a moderate SMR and one received a low SMR. The single medicine receiving a low SMR experienced a particularly large price decrease of -67.5%.

A clearer trend was observed for ASMR. Medicines receiving an ASMR III (moderate added clinical benefit) or ASMR IV (minor added clinical benefit) experienced average price decreases of -11.5% and -9.2%, respectively. By comparison, medicines receiving an ASMR V (no added clinical benefit) experienced a substantially larger average decrease of -36.9%.

Interestingly, ASMR III medicines did not experience a smaller average decrease than ASMR IV medicines in our sample.

Unmet medical need showed a similar pattern. When the medical need was considered unmet, the average price difference was -8.9%, compared with -16.0% when the need was considered partially or insufficiently met.

Positioning within the treatment pathway also appeared relevant. First-line treatments experienced an average price decrease of -10.8%, whereas decreases ranged from -17.4% to -19.1% for treatments positioned in second or later lines.

Taken together, these observations suggest that the value recognized at standard HTA assessment — including clinical benefit, added clinical benefit, unmet need, and therapeutic positioning — is an important consideration when anticipating the transition from early access to standard reimbursement.

The target population is also relevant

Medicines targeting very small populations generally experienced more limited price decreases. For target populations below 200 patients, average differences ranged from 0% to -7.5%.

At the other end of the spectrum, medicines with target populations exceeding 10,000 patients experienced an average decrease of -39.9%.

The relationship was not linear, but these results highlight another consideration when moving from early access to standard reimbursement: the potential evolution of the eligible population and associated budget impact.

This is particularly relevant when early access initially covers a restricted population, but standard reimbursement subsequently encompasses a broader group of patients.

Table 1: Observed Trends in Average Price Decrease from E

What about health economic assessment?

We also explored whether the Economic and Public Health Evaluation Committee (CEESP) health economic assessment was associated with the observed price differences. Medicines undergoing CEESP assessment showed a smaller average decrease than those without such an assessment, while no clear trend emerged according to the methodological acceptability of the economic model.

What does this mean for early access pricing strategy?

The main implication for manufacturers is that early access pricing and standard reimbursement pricing should not be approached as two independent decisions.

The environment at the time of early access is naturally important when setting the maximum compensation price. However, manufacturers should already be looking ahead to the conditions under which the product is likely to be assessed and priced at standard reimbursement.

Several questions should therefore be considered early:

• What SMR and ASMR levels can realistically be expected at standard assessment?
• Which clinically relevant comparators are likely to be considered, and what are their prices?
• Will the reimbursed population be broader than the early access population?
• How will the product ultimately be positioned within the treatment pathway?
• How could the target population and associated budget impact evolve?

Indeed, a product entering early access in a narrowly defined population with limited therapeutic options may face a very different environment at standard reimbursement if its population expands, new comparators become relevant or its added clinical benefit is not demonstrated.

Conversely, favorable therapeutic positioning, recognized added clinical benefit, limited alternatives, and a small target population coincided with the maintenance — or increase — of the early access compensation price in some cases.

Early access pricing should therefore be considered as the first step of a broader pricing strategy rather than as a standalone decision.

Final takeaways

In our sample of 34 medicines, standard reimbursement list prices were on average 14.5% lower than early access compensation prices, but outcomes varied considerably, from a 73.1% decrease to an 11.2% increase.

Several trends emerged. Greater recognized clinical value, unmet medical need, first-line positioning, and smaller target populations tended to coincide with more limited price decreases, while ASMR V (no added clinical benefit) and larger target populations were associated with larger decreases in our sample.

These findings remain purely descriptive and do not demonstrate causal relationships or predict the outcome of future CEPS negotiations. Pricing negotiations are multifactorial and confidential, and the analysis considers publicly available list prices only, without accounting for confidential rebates or contractual arrangements.

Nevertheless, the analysis highlights the value of considering the entire access pathway from the outset. Anticipating the expected HTA outcome, relevant comparators, therapeutic positioning, and potential evolution of the target population can help manufacturers better align their early access compensation strategy with the expected reimbursement environment in France.

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