Gordon LB, et al. - The association of monotherapy using the protein farnesyltransferase inhibitor lonafarnib with mortality rate was examined in children with Hutchinson-Gilford progeria syndrome (HGPS). Lonafarnib monotherapy was noted to be associated with a lower mortality rate after 2.2 years of follow-up compared with no treatment among these patients.

Methods

• Using conditional Cox proportional hazards regression, researchers compared contemporaneous (birth date ≥1991) untreated patients with HGPS matched with treated patients by age, sex, and continent of residency in this cohort study.
• In the treatment cohorts, patients from 2 single-group, single-site clinical trials were included (ProLon1 [n = 27; completed] and ProLon2 [n = 36; ongoing]).
• From a separate natural history study (n = 103), untreated patients were identified.
• January 1, 2018 was the cutoff date for patient follow-up.
• Oral lonafarnib (150 mg/m2) twice daily was received by treated patients.
• No clinical trial medications were administered to untreated patients.
• Mortality was noted to be the primary outcome.
• In the primary analysis, researchers compared treated patients from the first lonafarnib trial with matched untreated patients.
• The combined cohorts from both lonafarnib trials were compared with matched untreated patients in the secondary analysis.

Results

• Researchers identified 258 untreated and treated patients from 6 continents; 123 of these (47.7%) were female; 141 (54.7%) showed a known genotype, of which 125 (88.7%) were classic (c.1824C>T in LMNA).
• The primary cause of death, when identified (n = 73), was heart failure (79.4%).
• The median treatment duration of 2.2 years was noted.
• Follow-up was started at a median age of 8.4 (interquartile range [IQR], 4.8-9.5) years in the first trial cohort and 6.5 (IQR, 3.7-9.0) years in the combined cohort.
• Death of 1 patient (3.7%) among 27 patients in the first trial group and 9 patients (33.3%) among 27 patients in the matched untreated group were noted.
• A lower mortality rate was noted in association with treatment (hazard ratio, 0.12; 95% CI, 0.01-0.93; P=.04).
• In the combined cohort, 4 deaths (6.3%) among 63 patients in the treated group and 17 deaths (27.0%) among 63 patients in the matched untreated group (hazard ratio, 0.23; 95% CI, 0.06-0.90; P=.04) were reported.