Lonafarnib Clinical Studies in Hutchinson-Gilford Progeria Syndrome (Progeria)

»Lonafarnib Clinical Studies in Hutchinson-Gilford Progeria Syndrome (Progeria)
Lonafarnib Clinical Studies in Hutchinson-Gilford Progeria Syndrome (Progeria) 2018-05-22T20:54:22+00:00

Observational Cohort Study:  Association of Lonafarnib Treatment vs No Treatment with Mortality Rate in Children with Progeria

This observational cohort study assessed the mortality rate of Progeria patients treated with lonafarnib monotherapy versus those not treated with lonafarnib.  Treated patients were contemporaneously matched by gender, age and continent of residency with untreated patients.  Patients treated with lonafarnib monotherapy (150 mg/m2 twice daily) came from 2 single-group clinical studies (ProLon 1, n=27; and ProLon 2, n=36).

In ProLon 1, there was 1 death (3.7%) among 27 lonafarnib-treated patients and 9 deaths (33.3%) in the untreated matched group. Patients treated with lonafarnib had an 88% reduction in the risk of mortality compared to the untreated matched controls over an average follow-up period of 2.2 years (Hazard ratio 0.12; p=0.04) (Figure A). When ProLon 1 and ProLon 2 were combined there were 4 deaths (6.3%) among 63 lonafarnib-treated patients and 17 deaths (27%) in the untreated matched group. Patients treated with lonafarnib had a 77% reduction in the risk of mortality compared to the untreated matched controls over an average follow-up period of 2.2 years (Hazard ratio 0.23; p=0.04) (Figure B).

A. Patients Treated
in ProLon 1 (n=27)

B. Patients Treated in ProLon 1
and ProLon 2 (n=63)

Source: JAMA. 2018:319(16):1687-1695

Results were published in Journal of American Medical Association (JAMA). 2018;319(16):1687-1695. Click to open PDF.

Phase 2: Lonafarnib Monotherapy in Children with Progeria (ProLon 1)

This was an open-label dose adjusted Phase 2 trial. Twenty-six (26) patients were dosed with lonafarnib for 24-29 months.

Lonafarnib dosing was initiated at 115 mg/m2 and was increased to 150 mg/m2 after an adjustment period of at least 4 months. Dosage was reduced back to 115 mg/m2 for patients experiencing drug-related grade 3 or 4 toxicity and not responding to supportive care. Once dosage was reduced, patients were permitted to increase the dose of lonafarnib. Patients received oral lonafarnib either by capsule or liquid suspension dispersed in Ora-Blend SF or Ora-Plus (Paddock Laboratories, Inc.) every 12 ± 2 h for a period of 24–29 months.

The primary endpoint was the proportion of participants with successful rate of weight gain.  The a priori statistical design required 3 of the 25 enrolled patients to attain a >50% increase in slope for weight gain or a change from negative to positive slope.

Nine of 25 patients achieved success.

Additionally, carotid arteries demonstrated greater wall echodensity at the intima media and near adventitia in HGPS patients than in age and sex-matched controls.

Results were published in the Proceedings of the National Academy of Sciences of the United States of America. 2012:109:16666-16671. Click to open PDF.

For more information, please visit www.clinicaltrials.gov: NCT00425607.

Hutchinson-Gilford Progeria Syndrome (Progeria)

Photos Courtesy of The Progeria Research Foundation