FDA approval summary for lonafarnib (Zokinvy) for the treatment of Hutchinson-Gilford progeria syndrome and processing-deficient progeroid laminopathies

• DOI: 10.1016/j.gim.2022.11.003
• Publication Date: 2022-12-12T20:22:23Z
• Authors: Mari Suzuki; Linda J.B. Jeng; Solomon Chefo; Yan Wang; Dionne Price; Xiaohui Li; Jie Wang; Ruo-Jing Li; Lian Ma; Yuching Yang; Xinyuan Zhang; Nan Zheng; Ke Zhang; David B. Joseph; Hitesh Shroff; Jenny Doan; Michael Pacanowski; Patroula Smpokou; Kathleen Donohue; Hylton V. Joffe
• Keywords: Progeria; Orphan drug

The U.S. Food and Drug Administration recently approved lonafarnib as the first treatment for Hutchinson-Gilford progeria syndrome (HGPS) and processing-deficient progeroid laminopathies. This approval was primarily based on a comparison of patients with HGPS treated with lonafarnib in 2 open-label trials with an untreated patient cohort. With up to 11 years of follow-up, it was found that the lonafarnib treated patients with HGPS had a survival benefit of 2.5 years compared with the untreated patients with HGPS. This large treatment effect on the objective endpoint of mortality using a well-matched comparator group mitigated potential sources of bias and together with other evidence, established compelling evidence of a drug effect with benefits that outweighed the risks. This approval is an example of U.S. Food and Drug Administration's regulatory flexibility for a rare disease while ensuring that standards for drug approval are met.