FDA Approves Drug for Progeria, a Rare Disease Causing Rapid Aging in Children

Research behind the therapy could lead to other discoveries about heart disease as well as the aging process.

The FDA approved the first treatment to reduce the risk of mortality from progeria, an extremely rare disease that causes rapid aging and death, usually by age 15.

The approval was granted to Eiger BioPharmaceuticals, which partnered with the Progeria Research Foundation (PRF) on lonafarnib (Zokinvy). Lonafarnib is an oral farnesyltransferase inhibitor (FTI) that has shown survival benefit in children with Hutchinson-Gilford progeria syndrome and for the treatment of certain processing-deficient progeroid laminopathies in patients 1 year and older.

The drug is not approved for use in patients with other progeroid syndromes or laminopathies, the FDA said.

Eiger began supplying the drug for clinical trials in 2015, and partnered with PRF in 2018 with the aim of getting the drug through the FDA approval process. The application received Priority Review designation and the drug was designated as an Orphan Drug and also a Breakthrough Therapy. In addition, Eiger received a rare pediatric disease priority review voucher.

The company said the research behind the therapy could lead to other discoveries about heart disease as well as the aging process.

Patients with Hutchinson-Gilford progeria syndrome and progeroid laminopathies experience accelerated cardiovascular disease from the buildup of defective progerin or progerin-like protein in cells. Lonafarnib helps to prevent the buildup of the defective protein.

Effectiveness was shown in 62 patients from 2 single-arm trials who were compared with matched, untreated patients from a separate natural history study. Data based on information from the PRF International Patient Registry and clinical trials co-coordinated by PRF and Boston Children's Hospital demonstrated that lonafarnib reduced the incidence of mortality by 60% (P = .0064) and increased average survival time by 2.5 years through the maximum follow-up time of 11 years.

Without treatment, children with progeria die of heart disease at an average age of 14.5 years.

The approval took into account similarities in the underlying genetic mechanism of this disease and other available data, the FDA said.

“Hutchinson-Gilford progeria syndrome and progeroid laminopathies are rare genetic diseases that cause premature aging and death and have a debilitating effect on people’s lives,” said Hylton V. Joffe, MD, MMSc, director of the Office of Rare Diseases, Pediatrics, Urologic and Reproductive Medicine in the FDA’s Center for Drug Evaluation and Research. “With today’s approval, Zokinvy is the first FDA-approved medication for these devastating diseases. The FDA will continue to work with stakeholders to advance the development of additional new, effective and safe therapies for these patients.”

The most common adverse effects included nausea vomiting, diarrhea, infection, decreased appetite, and fatigue.

Zokinvy is contraindicated for co-administration with strong or moderate CYP3A inhibitors and inducers, as well as midazolam and certain cholesterol-lowering medications. Some patients treated with Zokinvy developed laboratory test abnormalities, such as changes in blood sodium and potassium levels, lowered white blood cell counts, and increased liver blood tests.

PRF, created by the family of Sam Berns after his diagnosis at age 2, also partnered with the National Institutes of Health on the treatment; there are about 400 children worldwide with the disorder. Berns died in 2014.