FDA Approves First Drug for Hutchinson-Gilford Progeria Syndrome

The US Food and Drug Administration (FDA) has approved lonafarnib (Zokinvy) capsules for the reduced risk of death from Hutchinson-Gilford progeria syndrome, as well as for the treatment of some processing-deficient progeroid laminopathies in patients 1 year and older.

With the indication, the Eiger BioPharmaceuticals therapy becomes the first approved for either disease.

The rare genetic conditions are associated with premature aging and death in affected patients, resulting in accelerated cardiovascular disease due to defective progerin or progerin-like protein in cells. It’s fairly common for patients to die from a major adverse cardiovascular event—stroke, heart failure, myocardial infarction, or otherwise—by the age of 15.

Prior to this first indication, lone treatment options entailed supportive patient care and complication-associated therapies.

Lonafarnib is a farnesyltransferase inhibitor, administered as an oral therapy, which prevents the buildup of progerin. Its efficacy for the treatment of Hutchinson-Gilford progeria syndrome was observed in 62 patients from a pair of single-arm trials compared to control patients from a separate natural history trial.

Patients with the syndrome treated with lonafarnib reported an increased lifespan of 3 months through the first 3 years of treatment versus control—and an increase of 2.5 years through a maximum follow-up period of 11 years.

Lonafarnib’s approval for the treatment of certain, rare processing-deficient progeroid laminopathies was based on observed similarities in underlying genetic mechanisms of disease and other available data.

Commonly observed adverse events in the supporting-data trial included nausea, vomiting, diarrhea, increased appetite, and fatigue.

The FDA indicated that lonafarnib is contraindicated for co-administration with strong or moderate CYP3A inhibitors and inducers, as well as midazolam and certain cholesterol-lowering therapies.

The therapy’s application previously received Priority Review, Orphan Drug Designation, and Breakthrough Designation.