Access to innovation through clinical trials and the national early access program for patients with lung cancer in France: focus on atezolizumab and durvalumab.

PURPOSE: Tumor genomic profiling and PD-L1 testing mean lung cancer management can be tackled through a personalized approach. Targeted therapies and immunotherapy are necessary to improve survival and preserve the patients' quality of life. Early access to innovation before marketing authorization (MA) is possible in France through clinical trials and an early-access program called a Temporary Authorization for Use (ATU), which is a unique regulatory system in Europe. This study aims to assess the impact of early access to innovation through clinical trials and ATUs in thoracic oncology. METHODS: Data from clinical trials between 2018 and 2021 and ATUs between 2005 and 2019 were collected internally and assessed for drugs in thoracic oncology, with specific focus on 2 ATUs, respectively, atezolizumab and durvalumab. RESULTS: From 2018 to 2021, the National Agency for the Safety of Medicines and Health Products authorized 145 clinical trials in lung cancer. Between 2005 and 2019, 19 drugs obtained an EU MA or an MA extension for a therapeutic indication in lung cancer. During this period, 11 of these drugs were granted an ATU, corresponding to 6851 patients treated. Of this total number of patients, data were collected for 33.1% and 71.2%, who received durvalumab and atezolizumab, respectively. Real-life efficacy data were consistent with the clinical trial data. CONCLUSION: Over the past 15 years, clinical trials and the French early access program have allowed considerable early access to therapeutic innovation in real life for patients, especially in thoracic oncology.

Survival, cost and added therapeutic benefit of drugs granted early access through the French temporary authorization for use program in solid tumors from 2009 to 2019.

Decisions on market authorization (MA) and reimbursement have different durations across countries because of health technology assessment (HTA) procedures and negotiations between manufacturers and national authorities. To overcome this delay, France has implemented a Temporary Authorization for Use (ATU) program that allows early access to drugs before MA, in order to treat patients with unmet medical needs. The objectives of our study were to establish the added therapeutic benefit (ATB) of ATUs for solid tumors and to investigate the correlations between three tools evaluating ATB and survival outcomes and drug costs. Data on ATUs granted from January 2009 to December 2019 to treat solid tumors were analyzed. An assessment of their ATB was conducted using the American Society of Clinical Oncology-Value Framework (ASCO-VF), the European Society for Medical Oncology-Magnitude Clinical Benefit Scale (ESMO-MCBS) and the French HTA criterion, clinical added value (CAV). The latter score determines reimbursement and national market access. Thirty-five drugs in 39 indications were granted ATUs. All of them obtained MA and derived a clinical benefit to be reimbursed by the Social Security. Twenty-eight (71.8%) had CAV compared to preexisting therapies. 24/38 (63.2%) had a 4-5 ESMO-MCBS score and 19/33 (57.6%) had an ASCO-VF score over 45. No correlations were found between cost, PFS, OS, CAV and ASCO-VF score, while high ESMO-MCBS scores were correlated to OS. In conclusion, many patients were treated with innovations before MA thanks to ATU, although there are discrepancies between ATB scales, hence the importance of international collaboration in the evaluation of innovative therapies.

Comparative study on anticancer drug access times between FDA, EMA and the French temporary authorisation for use program over 13 years.

INTRODUCTION: The cancer incidence continues to rise worldwide. Medical innovation has a major impact on patient survival, but within drug development, it can take more than 10 years to obtain marketing authorisation (MA). The time required for access to therapeutic innovation remains critical, so France has developed a specific expanded access program named ATU, which allows the administration of drugs before the European Medicines Agency (EMA) approval. The purpose of this study is to put in perspective the average time to access antineoplastic drugs worldwide, taking into account ATU, US Food and Drug Administration (FDA) and EMA approvals. METHODS: The ATU system allows the use of a medicine before its MA, under exceptional conditions. All antineoplastic drugs in oncology that have benefited from the ATU system are analysed in terms of tumour site, biomarkers and number of patients who have access to the drug. RESULTS: Between 1st January 2007 and 31st December 2019, 36 of 64 drugs (56.2%) that received MA in oncology were assigned an ATU, to the benefit of 16,927 patients. Thanks to the ATU, 25 of 36 drugs (69.4%) were made available early, on average 203 d (95% CI, 76-330) before FDA approval and on average 428 d (95% CI, 272-583) before EMA approval. Only three of 36 drugs were approved by the EMA before the FDA, and the average time lapse between European MA and FDA approval for these 36 drugs was 216 d (95% CI, 140-293). CONCLUSION: This article demonstrates that the ATU system allows patients to benefit from therapeutic innovations before MA in Europe and USA, with full coverage by the healthcare system.

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

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.