Access to innovation through the national early access program and clinical trials for patients with malignant melanoma

Abstract

Background: The arrival of immunotherapies and targeted therapies challenged the authorities to make them available as soon as possible. France has effective tools, such as clinical trials (CTs) and a national early access program (temporary authorizations for use [ATUs] and temporary recommendations for use [RTUs]), allowing the use of innovative drugs, whether or not they have been authorized or used off-label, for cases that have reached a therapeutic impasse.

Methods: The methodology involved real-time data collection from ATUs, RTUs (between September 1, 2009 and September 1, 2019), and CT authorizations (from December 1, 2017 to September 1, 2019) that were filed and reviewed by the French National Agency for Medicines for metastatic melanoma (MM).

Results: In total, 45 CTs were authorized for MM (51% early phase trials and 44% phase 2 and 3 trials), mainly for the metastatic line (86%) and with an industrial sponsor (73%). Immunotherapies and targeted therapies (63% and 24%, respectively) mostly were used in combination. Three RTUs were authorized for the adjuvant treatment of MM, whereas 13 drugs were available through nominal ATUs (nATUs), of which 5 were awarded a cohort ATU (cATU). This enabled the treatment of 6538 patients (28% through nATUs and 72% through cATUs). All of these drugs were granted marketing authorization and were included in the reimbursement list.

Conclusions: Thanks to CTs and the national early access program, patients in France have been able to benefit from innovative MM treatments.

Lay summary: Several tools allow the use of innovative drugs in France, even if they are not yet authorized or used off-label. From December 1, 2017 to September 1, 2019, 45 clinical trials have been authorized for metastatic melanoma, mostly using immunotherapy (63%) and targeted therapy (24%) at an early phase (51%). Since 2010, the national early access program has treated 6538 patients, including 28% under nominative temporary authorizations for use and 72% under cohort temporary authorizations for use. Fourteen drugs are available through nominative temporary authorizations for use, and 5 are available through cohort temporary authorizations for use, and all of these drugs were granted marketing authorization.

Keywords: France; clinical trials; compassionate use trials; data collection; delivery of health care; drugs investigational; empathy; humans; malignant melanoma.

Figure 1

The most common classes of drugs found in malignant melanoma clinical trials are shown according to the number of trials between December 1, 2017 and September 1, 2019. IT indicates immunotherapy; TT, targeted therapy.

Figure 2

This is a breakdown of clinical trials for the treatment of malignant melanoma according to treatment lines between December 1, 2017 and September 1, 2019.

Figure 3

This is a breakdown by drug of the number of patients who were included in a cohort temporary authorization for use (cATU) or who were granted a nominative temporary authorization for use (nATU) for the treatment of malignant melanoma between September 1, 2009 and September 1, 2019. LAG 525 indicates lymphocyte‐activation gene 525; MA, market authorization.

Figure 4

This is a timeline of granting nominative temporary authorization for use (nATU) and providing cohort temporary authorization for use (cATU), followed by awarding of marketing authorization (MA), and pricing and reimbursement schemes for the drugs used for the treatment of malignant melanoma between September 1, 2009 and September 1, 2019. LAG 525 indicates lymphocyte‐activation gene 525.

Figure 5

Efficacy data are illustrated for patients who were covered by cobimetinib, vemurafenib, and pembrolizumab cohort temporary authorizations for use according to Immune‐related Response Criteria and Response Criteria. ORR indicates overall response rate; W, week.