By Erfan Akbraian, Analyst
France’s National Agency for the Safety of Medicines and Health Products (ANSM)1 governs the early access program called autorisation temporaire d’utilisation (ATU). The ANSM are expected to implement changes set by the French social security law to the nominative ATU program later this year to ease the cost burden associated with the ATU.
The EU transparency directive states pricing and reimbursement (P&R) decisions should be made within a 180 days2 timeframe. In most cases this is not the reality, of the 38 orphan drugs in 2015 – 2017, the average delay from European medicines agency (EMA) market authorisation (MA) to commercialisation in France took 551 days3. With an increase in number of orphan drugs, cell and genes therapies achieving European MA, the ATU provides early paid for access for orphan drugs undergoing P&R and/or prior to EMA approval. Nominative (named patient) and cohort (group of patients) are the two types of ATU programs.
Nominative and Cohort ATU criteria for serious life-threatening therapies:
The nominative ATU application process is physician driven. There is no opportunity for the manufacturer to engage with the authorities, to provide a strong rationale to include their therapy on the nominative ATU program. Therefore, alongside a comprehensive physician justification and good efficacy and safety data, a therapy can be included on the nominative ATU list. In 2018, 5,642 and 15,987 patients4 had access to medicines via the cohort ATU and nominative ATU programs, respectively.
Expected changes for the nominative ATU:
French treating physicians generally are not budget conscious, in the 2018 ANSM report there appears to be three times as many patients on the nominative program compared to cohort4. This may be driven by the high unmet need for these rare disease patients and the low prevalence numbers which would be more convenient for the named patient program. Another reason may be the manufacturer did not seek a cohort ATU. In recent years there has been an increasing trend of approvals of therapies for rare disorders. It is difficult to find a price comparison for many of these therapies and due to the free pricing nature of the ATU this leaves a large budget impact (BI) for French authorities, which has exceeded €1 billion per year since 2014.6
- To reduce the BI of the ATU the French authorities aim to implement stricter eligibility criteria by capping the number of nominative requests per drug, by demanding drugs show a stronger therapeutic benefit. Additional criteria include the clinical trial must have already started and not be in the planning / submitted phase. 6,7
- Currently the manufacturer sets the price of therapy for nominative ATU and must pay back the price difference of up to €20,000 per patient once the therapy is commercialised in France. To reduce the BI the French authorities, aim to set the price of nominative ATU drugs and unlike before, the price will be confidential and not published.8,9,10
Implications for manufacturers:
These modifications to the nominative ATU criteria would lead to products late in the development cycle being approved, as they would need to possess strong benefit: risk data. Manufacturers with nominative ATU approval should expect lower uptake potential of their therapy as the number of nominative ATU requests per therapy will be capped. Therefore, the proxy pathway to commercialise very high cost therapies with a small population is no longer available and manufacturers would need to opt for full HTA submission. Also, with the French authorities having more responsibility in determining the cost of the therapy, a lower price is likely. These changes could therefore decrease the pre-commercialisation revenue opportunity through the nominative ATU program. As well as impact the price potential of a therapy in the long term, as the ATU price historically creates a price ceiling for discussions with Comité économique des produits de santé (CEPS).
- ANSM: Notice to applicants for marketing for Temporary authorisation for Use (ATU), 2015
- P4A primary research interview