OBJECTIVES: Hereditary angioedema is a rare genetic disease, characterized by occurrence of subcutaneous/submucosal, recurrent edema. Lanadelumab is a prophylactic treatment authorized in Europe since Nov18. It benefited from an Authorization for Temporary Use (ATU)/post-ATU in France since Oct18. If small patient numbers and short timelines are challenges, ATUs provide real world evidence (RWE) for assessment by Haute Autorité de Santé (HAS) and support early evidence generation plans (EGP).

METHODS: The lanadelumab EGP consisted of: (1) ATU collecting safety, effectiveness, QoL, (2) SERENITI, ambispective research enrolling ATU, post-ATU and early commercial period patients, collecting long-term utilization, effectiveness, safety, QoL (3) SERENITI+SNDS, linkage to French claims database SNDS studying disease management in France, utilization, effectiveness and economic impact of lanadelumab. The EGP is evaluated by number of participants, length of follow-up over enrichment, valorization of results.

RESULTS: The ATU included 78patients in 5months. Interim analysis provided HAS with results on 35patients treated up to 5months (vs 27patients in pivotal study). Due to its quality, it was fully reported in the HAS opinion, and used in health technology assessment processes in other countries worldwide. SERENITI enrolled 162patients treated 18-50months. The SERENITI+SNDS will analyze all patients treated in France over the first 4years of availability and will link the 162pts of SERENITI. The French EGP will contribute to lanadelumab value demonstration by HAS and positioned France as first enrolling country in the European post-launch study. It has already led to 6 scientific communications (Jun19-Dec22).

CONCLUSIONS: RWE generation is challenging in rare diseases where patients are few and health authorities request reliable data to motivate their decisions. An EGP, continuum based on the enrichment in patients and follow-up length from a high-quality data collection during early access framework in France, is possible with high performance and acceptability by health authorities across the world.