New ATU system: what changes for pharmaceutical companies in 2021?

The Temporary Authorization for Use (ATU) system allows patients with serious diseases to obtain early access to innovative medicines. Long considered a strength of the French model, the ATU system has now become extremely complex for pharmaceutical companies due to constant legislative changes. Article 38 of the Social Security Financing Bill for 2021 (PLFSS 2021), published in October 2020, proposes a global revision of the current derogatory access to medicines, by reorganizing the ATU around two main access categories: early access and compassionate access. In this article, we decipher the major changes in these systems and their consequences for pharmaceutical companies.

The temporary authorization of use (ATU) system: an opportunity for patients

In France, the average time between marketing authorization (MA) and market access process completion is about 500 days: a relatively long time for patients with life-threatening conditions or suffering from a rare, serious or disabling disease for which there is no therapeutic alternative.

To meet these needs, the French system provides an exceptional procedure for drugs that do not have a MA or still still in the P&R process: the ATU (Temporary Use Authorization).

This system was initiated in 1994 to make anti-HIV products available to patients (LEEM). Today, the issued ATU are mainly for anti-cancer drugs (ANSM).

In fact, in 2020, 45% of the 29 specialties authorized under cohort ATU were in the oncology field (ANSM). As promising but costly innovations such as CAR-T cell therapy reach the market, adjustments appear necessary to preserve the durability, excellence and attractiveness of the ATU system and thus guarantee quick access to innovations for French patients.

In this context, this dispositive was recently revised through the Article 38 of the PLFSS 2021 and thus reorganized the 5 current ATU categories (Temporary Authorization for Use (ATU), cohort ATU, nominative ATU, extension ATU, post-ATU, direct post-MA) into two main access systems:

• an early access authorization (EAA) system for drugs that are likely to be innovative before their MA.
• a compassionate access authorization (CAA) system for drugs that are not intended to obtain a MA but which meet a therapeutic need in a specific situation.

Early Access Authorization (EAA): merge of the cohort and post-ATU systems

The new article L. 5121-12 defines “early access” as:

“the use, on an exceptional basis, of certain medicinal products, in specific therapeutic indications, intended to treat rare or disabling diseases.”

The conditions for granting early access authorizations are the same as those for cohort ATU (absence of appropriate treatment, the treatment emergency, strong presumption of efficacy based on the clinical trials results). In addition, to benefit from this authorization, the drug must be presumed to be innovative, “based on a comparator clinically relevant”. However, the lack of details in the PLFSS 2021 on this subject raises questions regarding the evaluation modality of innovative conditions and thus could lead to a stricter selection process than the previous procedure.

The EAA can be granted to:

• drugs that do not have a MA for the indication, providing the pharmaceutical company commits to filling an MA application within a defined period. (corresponding to the former cohort ATU model)
• drugs that have a MA for the indication considered but is still in the P&R process (corresponding to the former post-ATU model). This second option is only applicable if the pharma company submits an application for reimbursement within one month of obtaining the MA.

The transformation of the cohort ATU and post-ATU into a single early access system will highly simplify the legibility and practical application of the system for pharma companies.

Unlike the previous ATU system, which was exclusively evaluated by the ANSM, the EAA would be granted by the French HTA Agency (HAS), after the ANSM notice. Besides, another new feature is that the time required to enter the early access system should be reduced and not exceed 80 days, whereas the average time required for cohort UTA is currently 135 days.

Additionally, the EAA is subject to compliance, by the pharma companies, of a Protocol for therapeutic use (PUT) and data collection defined by the French HTA Agency (previously established by the ANSM under the old system); collected data includes efficacy, adverse effects and the actual conditions of use of the drug.

These new interventions by the French HTA Agency, in the evaluation of the EAA and the PUT, demonstrate an ambition to reinforce the framework and better control the presumption of the efficacy of the drug. This could have the advantage of limiting the number of coverage interruptions for drugs which, previously authorized by the ANSM under the old system, could have been rejected for reimbursement by the French HTA Agency. Therefore, this new role for the French HTA Agency could strengthen the selection, according to new innovation criteria, of drugs that can benefit from early access.

As for the financing modalities, the treatment is still covered by the health insurance. In this new system, the pharma company sets the drug price by defining a maximum allowance. This allowance will be adjusted when the net reference price is set by the CEPS (Economic Committee on Health Products) in the form of a rebate. The PLFSS 2021 has thus abolished several rebate mechanisms, thereby simplifying the financial regulation of the early access system.

Compassionate Access Authorization (CAA): transformation of nominative ATU

Nominal ATUs became increasingly similar to “compassionate” treatments, prescribed by a physician in evaluation of a benefit-risk assessment, but whose beneficial effect cannot be deduced from a clinical trial.

In response to this observation, the new article L. 5121-12-1 introduces the possibility of “compassionate access for certain medicinal products“. These products are not necessarily innovative and  not always intended to obtain a MA in the considered indication but which meet a therapeutic need. The CAA can thus be granted to a named patient when there is no appropriate treatment and when the efficacy and safety are presumed given the available clinical data and is not subject of research involving the human being.

Similar to the nominative ATU, the CAA is granted by the ANSM at the request of prescribers, for one year and renewable, for a drug that does not have MA in any therapeutic indication.

Recently, the CAA can also be authorized for a drug with a MA in another indication, on the condition that the drug has been discontinued from the market.

Like the EAA, each CAA is associated with a Protocol for therapeutic use (PUT)  established by the laboratory and validated by the ANSM (and not by the French HTA Agency as in the case of the EAA), the data collection of which is the responsibility of the laboratory. The laboratory must therefore be informed of the implementation of a CAA by the ANSM, but is not involved in patient selection.

The article 38 of the PLFSS implements the revision of the Temporary Authorization for Use (ATU) system. This evolution provides an opportunity for patients to get a faster access to innovative medicines, but also for healthcare industry players by giving them a better visibility of the system. A dispositive intending to be faster but also simpler, particularly for financial regulations. However, we must be alert to the strengthening of selection criteria and the increasing role of the French HTA Agency in the choice of drugs eligible for early access. The early and compassionate access dispositive are scheduled to be effective no later than July 1, 2021. At Alcimed, we are ready to support our clients in the construction of their future temporary authorization project!

About the author, 

Eugénie, Consultant in Alcimed’s Healthcare team in France