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.
Keywords
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Article info
Publication history
Published online: December 12, 2022
Accepted:
November 1,
2022
Received in revised form:
October 31,
2022
Received:
June 10,
2022
Publication stage
In Press Corrected ProofIdentification
Copyright
Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics.
