Early access authorisation : a positive initial report and refined assessment methods

HAS and the ANSM are publishing an initial report on the medicinal product early access authorisation (AAP) procedure, set up on 1^st July 2021. In 10 months, around one hundred early access authorisation applications (pre-MA and post-MA) have been submitted to HAS by pharmaceutical companies. On 30 April, 50 decisions had already been issued, leading to granting of early access authorisation in 80% of cases. These authorisations concern innovative medicinal products answering to unmet needs and for severe, rare or incapacitating diseases. They therefore benefit patients directly by providing them with rapid access to a medicinal product with no alternative.

A positive outcome 10 months after the effective date of the reform

From the summer, and the creation of this new procedure, HAS and the ANSM authorised medicinal products which brought hope for patients in a therapeutic stalemate. For example, HAS, after analysis by the ANSM, granted early access authorisations for Trodelvy® and Keytruda® (see press release), medicines potentially benefiting thousands of women with triple-negative breast cancer each year; for Ronapreve® (see press release), effective treatment against the COVID-19 Delta variant, early access to which, granted very rapidly, made this treatment accessible right in the middle of the variant wave, thus preventing some patients contracting severe forms of the disease; or event the Kaftrio®/Kalydeco® combination (see press release) which represents real hope in the treatment of cystic fibrosis in certain patients over the age of 6.

Another reason to be satisfied, application processing time is short, enabling rapid access to innovative treatments. Whereas regulatory processing time is set at 90 days, together both agencies can boast mean processing times of around 60 days. Concerning products aiming to treat or prevent severe forms of COVID-19, mean processing time has been reduced to 35 days, to be able to meet this medical need as early as possible.

It should also be noted that out of the 50 decisions returned, 23 were supported by the written contribution from a patient's association and 11 associations were heard by the Transparency Committee.

A new version of the doctrine to refine the procedure

In light of this initial report, but also of the feedback from the permanent dialogue with the French National Agency for Medicines and Health Products Safety ANSM) firstly, and with manufacturers secondly, or even with representatives of patient's associations, HAS is changing its assessment methods.

Therefore, in its new version, HAS’s early access doctrine included refined criteria and subcriteria to determine whether an appropriate treatment is available or not, especially with regard to past experience with the first applications. Therefore, exceptionally, especially where a treatment is likely to provide an answer to a health emergency, clinically relevant treatment options may not be considered appropriate treatments.

The other major change made to the doctrine covers presumed innovation. The doctrine now specifies that a medicinal product likely to be innovative in the context of early access authorisation must fulfil the following three conditions, along with the additional elements in bold:

• It is a novel treatment regimen likely to offer patients a substantial change;
• It has a suitable development plan and clinical findings supporting a presumptive benefit for the patient in the context of the existing therapeutic strategy;
• It meets an unmet or insufficiently met medical need.

In view of the wide range of clinical scenarios encountered over the first 10 months, HAS confirms that it is not possible to envisage a single definition of presumptive innovation. To this effect, HAS is assessing various components, taking the specific features of certain therapeutic areas into account especially, for which the medical need is significant with regards to the disease-related mortality and morbidity.

See the new version of HAS’s assessment doctrine on early access authorisations on HAS’s website: Medicinal product early access authorisation: HAS assessment doctrine (has-sante.fr)

Two options for early access authorisation applications

Early access authorisation (AAP) is an exceptional derogation-based scheme enabling the early availability and funding of a medicinal product (for one or more indications) before its reimbursement by the National Health Insurance under common law. The objective is to fast-track access to this medicinal product for patients. Early access authorisation can be granted on request by the pharmaceutical company for treatment meeting each of the following conditions (specific in article L.5121-12 of the French code of public health) :

• when it does not yet have marketing authorisation, the efficacy and safety of the medicinal product are strongly presumed based on the results of clinical trials ;
• it is indicated in a severe, rare or incapacitating disease ;
• there is no appropriate treatment;
• the initiation of treatment cannot be delayed;
• the medicinal product is presumptively innovative, particularly compared to any clinically relevant comparator.

The first criterion is assessed by the ANSM, the other four by HAS.

Two scenarios are possible :

• The early access application is made before marketing authorisation (pre-MA) :
  The ANSM first assesses the medicinal product’s benefit/risk ratio. If it issues an unfavourable opinion, HAS assesses it with respect to the criteria set out in the previous section. HAS’s decision must be issued within 90 days from the date the application becomes administratively admissible. If authorisation is issued, the pharmaceutical company undertakes to submit an MA application within 2 years at most.
• The application is made after marketing authorisation (post-MA) :
  Once the marketing authorisation granted to a medicinal product, its price is set by the healthcare products pricing committee, generally by negotiating with the company operating the medicinal product. As this phase can take several months, the pharmaceutical company can request post-MA early access authorisation for all or part of the indication on the marketing authorisation obtained.
  In any case, the pharmaceutical company applying for early access undertakes to provide the medicinal product to patients in the 2 months following issue of early access, and to submit a request for inclusion on reimbursement lists further to granting of MA.

In any case, the pharmaceutical company applying for early access undertakes to provide the medicinal product to patients in the 2 months following issue of early access, and to submit a request for inclusion on reimbursement lists further to granting of MA.