Improving the Implementation of Personalized Medicines into Clinical Practices with Early Access Programs: the Example with Olaparib in France

Key Contextual Factors

• The first European marketing authorization for olaparib was granted in 2014 for the maintenance treatment of adult patients with platinum-sensitive relapsed BRCA-mutated high grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete response or partial response) to platinum-based chemotherapy. Additional clinical data showed an interest of this molecule to treat newly diagnosed ovarian cancer with a BRCA 1/2 mutation. As this drug was already on the market, a risk for off-label use was identified by healthcare professionals, triggering the need to implement a secured access through an early access program for this new indication.
• Two regulatory frameworks existed in France to secure the access to medicines for unapproved indications, managed by the national agency for the safety of medicines and health products

• RTU: Temporary Recommendation of Use aims to supervise and secure the prescription of a marketed drug for an off-label indication that takes place in France.
• ATU: Temporary Authorization for Use aims to ensure early access for a new drug indication that does not yet have a marketing authorization.

• This early access program is evolving to gain even more efficiency and was revised in July 2021.

Key Components/Steps

• Alert from the French expert group working on the development of a clinical practice guideline for the initial management of epithelial ovarian cancer, of a risk for off-label use with olaparib for newly diagnosed ovarian cancer with a BRCA1/2 mutation, following the results of the SOLO1 trial.
• INCa formalized an alert to ANSM for the need to assess a RTU to cover this new indication in October 2018.
• Instead of a RTU, an ATU for extension of indication was granted started in 11 March 2019.
• The extension of marketing authorization was approved on 26 April 2019 by the CHMP (Committee for Medicinal Products for Human Use- EMA).
• The clinical practice guidelines for the initial management of epithelial ovarian cancer, endorsed by INCa, was published in November 2019, positioning olaparib in the cancer treatment strategy.
• ATU stopped on 16 January 2020 after the award of the extension of indication of the European marketing authorization.

Main Impacts / Added Value

• While awaiting for the European marketing authorization and the national decision for reimbursement, the ATU program enabled to provide a secured access to olaparib for its extension of indication for maintenance treatment of adult patients with advanced (FIGO stages III and IV) BRCA1/2-mutated (germline and/or somatic) high-grade epithelial ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy.

Lessons Learned

• Strong interactions between INCa and practicing healthcare professionals, clinician experts help identifying uncover needs, potential off-label use. INCa enabled a coordinated approach to better implement olaparib into clinical practices by being involved at the different steps of the drug circuit: anticipation, early access, implementation into clinical practice guidelines.
• The ATU program was chosen over the RTU as the marketing authorization holder submitted an application for implementing an ATU program. The RTU remains an interesting leverage to provide a secured access to off-label indications when pharmaceutical companies do not file the marketing authorization dossier for the corresponding indication.

Download PDF