The reformed early access scheme in France – has it met it’s objectives?

What is the reformed early access scheme?

The 2021 Social Security Finance Law (Loi de financement de la sécurité sociale, LFSS) made provision for overhauling the early access scheme in France. As of 1^st July 2021, two new schemes – the early access scheme (accès précoce) and the compassionate access (accès compassionnel) scheme – were introduced. These replace the previous schemes, the temporary use authorisation (autorisation temporaire d’utilisation, ATU) scheme and the recommendation for off-label use (recommendation temporaire d’utilisation, RTU) scheme.

Early Access

The early access scheme replaces the ATU de cohorte (ATUc, temporary use authorisation for a group of patients), the ATU EIT (temporary use authorisation for indication extensions of drugs which have marketing authorisation in a different indication), the post-ATU scheme (drugs for which an ATU is requested after marketing authorisation has been granted but before reimbursement listing) and the post-MA direct access schemes. Eligible are drugs which meet the following five criteria:

• Is to treat a rare, serious or disabling disease
• There is no therapeutic alternative
• Treatment cannot be deferred
• Is presumed to be innovative
• The risk-benefit profile is presumed to be favourable.

Manufacturers must commit to applying for MA within two years.

All requests for early access are evaluated by the HAS.

The company must commit to respect the protocol for therapeutic use established for the drug (compiled by the manufacturer and approved by the HAS), and to finance real-life data collection.

Compassionate Access

The compassionate access scheme replaces the former ATU nominative (temporary use authorisation for a named patient) and the RTU schemes. This scheme is for medicines which are not necessarily innovative and which are not intended to be commercialised in the indication in question, but which meet a therapeutic need. To be eligible, the drug in question must fulfil the following criteria:

• There is no clinical research underway for commercial purposes
• There is no appropriate treatment
• The drug’s efficacy and safety are presumed based on the available clinical data.

Under the compassionate access scheme, drugs can be granted either:

• compassionate access authorisation (granted for a period of one year, renewable): open to medicines which do not have MA in any indication
• compassionate prescription (granted for a period of three years, renewable): open to medicines which have MA in another indication.

The National Agency for Drug Safety (Agence nationale du sécurité du médicament et des produits de santé, ANSM) evaluates and takes decisions pertaining to compassionate access.

The company must commit to respect the protocol for therapeutic use established for the drug and patient data collection.

Pricing and Reimbursement

Both early access and compassionate access automatically guarantee full (ie 100%) reimbursement.

For drugs subject to early access, manufacturers are free to set the price.

For drugs subject to compassionate access, if the drug already has a price in another indication, this price applies. Otherwise, either the manufacturer can freely set the price or a flat-rate (per patient) is established.

Financial Regulation

Annual clawbacks are due in relation to drugs with early access or compassionate access. The rebate is determined according to legislated rates.

In addition, a final rebate is due once a price is negotiated with the Pricing Committee (Comité économique des produits de santé, CEPS).

What are the aims of the new scheme and have they been met?

The new scheme aims to simplify the mechanisms for early access, and to ensure faster access to new medicines for patients without other treatment options.

However, the reformed scheme is similarly complex and clawbacks are still unpredictable for manufacturers. Moreover, in the case of accès précoce the establishment of a protocol for therapeutic use and collection of data has created several bottlenecks in the implementation of the reform. Hospitals have to free up resources for the collection of data which is not always feasible and manufacturers need to align the protocol they put in place with the requests of the HAS which considerably delays the HAS’ decision and the start of patient access.

To date, 20 decisions concerning 18 products or product combinations have been made since implementation of the reform. Of these, HAS has granted early access to 16, including most recently (in January 2022):

• GSK’s Xevudy (sotrovimab) as a treatment for adults and adolescents aged 12 years and over who are infected with COVID-19 and who present a risk of developing a severe form of the disease.
• Pfizer’s Paxlovid (nirmatrelvir/ritonavir) as a treatment for adults infected with COVID-19 who do not require oxygen therapy and who are at high risk of developing a severe form of the disease.

Sources:

1. Réforme de l’accès dérogatoire aux médicaments. Accessed at has-sante.fr January 2022
2. Prescription et délivrance des médicaments: médicaments en accès précoce ou compassionnel. Accessed at vidal.fr January 2022
3. Autorisation d’accès précoce aux médicaments : doctrine d’évaluation de la HAS. Accessed at has-sante.fr January 2022
4. Réforme de l’accès dérogatoire aux medicaments: renforcer l’accès aux traitements innovants pour les patients en impasse thérapeutique. Accessed at https://ansm.sante.fr January 2022
5. Covid-19: accès précoce accordé aux Paxlovid en traitement curatif. Accessed at has-sante.fr January 2022
6. Covid-19: accès précoce accordé au Xevudy en traitement curatif. Accessed at has-sante.fr January 2022