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

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

doi:10.1016/j.gim.2022.11.003

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

Genet Med. 2023 Feb;25(2):100335. doi: 10.1016/j.gim.2022.11.003. Epub 2022 Dec 12.

Authors

Mari Suzuki¹, Linda J B Jeng², Solomon Chefo³, Yan Wang³, Dionne Price³, Xiaohui Li⁴, Jie Wang⁴, Ruo-Jing Li⁴, Lian Ma⁴, Yuching Yang⁴, Xinyuan Zhang⁴, Nan Zheng⁴, Ke Zhang⁵, David B Joseph⁵, Hitesh Shroff⁶, Jenny Doan², Michael Pacanowski⁴, Patroula Smpokou², Kathleen Donohue², Hylton V Joffe²

Affiliations

¹ Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD. Electronic address: mari.suzuki@fda.hhs.gov.
² Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD.
³ Office of Biostatistics, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD.
⁴ Office of Clinical Pharmacology, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD.
⁵ Office of New Drugs, Office of Immunology and Inflammation, Division of Pharmacology/Toxicology for Immunology and Inflammation, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD.
⁶ Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD.

PMID: 36507973
DOI: 10.1016/j.gim.2022.11.003

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00425607 NCT00916747.

Keywords: Farnesyltransferase inhibitor; Hutchinson-Gilford progeriasyndrome; Lonafarnib; Processing-deficientprogeroid laminopathies; Regulatory flexibility.

Published by Elsevier Inc.

MeSH terms

Humans
Lamin Type A / genetics
Piperidines / therapeutic use
Progeria* / drug therapy
Progeria* / genetics
Pyridines / therapeutic use
United States

Substances

lonafarnib
Lamin Type A
Piperidines
Pyridines

Associated data

ClinicalTrials.gov/NCT00425607
ClinicalTrials.gov/NCT00916747