Eiger and AnGes’ Zokinvy Approved in Japan for Rare Progerias

Rare Daily Staff

Japan’s Ministry of Health, Labour and Welfare has approved Eiger BioPharmaceuticals’ and AnGes’ Zokinvy (lonafarnib) as a treatment for Hutchinson-Gilford progeria syndrome (HGPS) and processing deficient progeroid laminopathy (PDPL).

Collectively known as progeria, Hutchinson-Gilford progeria syndrome (HGPS) and processing deficient progeroid laminopathy (PDPL) are devastating ultra-rare and fatal pediatric diseases that cause dramatically accelerated aging and premature death. The main cause of death is heart attack or stroke due to severe hardening of the arteries.

HGPS is caused by a point mutation in the LMNA gene, yielding the farnesylated aberrant protein, progerin. Progeroid laminopathies are genetic conditions of accelerated aging caused by a constellation of mutations in the LMNA and/or ZMPSTE24 genes yielding farnesylated proteins that are distinct from progerin.

Children with HGPS commonly die of the same heart disease that affects millions of normally aging adults (arteriosclerosis), by an average age of 14.5 years. Disease manifestations include severe failure to thrive, scleroderma–like skin, global lipodystrophy, alopecia, joint contractures, skeletal dysplasia, global accelerated atherosclerosis with cardiovascular decline, and debilitating strokes.

The approval was based on the positive results of two pivotal clinical trials demonstrating that Zokinvy, an oral disease-modifying agent which targets the cause of progeria, lowered the risk of death in children by 72 percent and extended life by an average of 4.3 years in children and young adults with HGPS.

Zokinvy is a first-in-class disease-modifying agent that blocks the accumulation of defective progerin and progerin-like proteins which leads to cellular instability and premature aging in children and young adults with progeria. Zokinvy has demonstrated a statistically significant survival benefit in children and young adults with HGPS.

The most commonly reported adverse reactions were gastrointestinal (vomiting, diarrhea, nausea), and most were mild or moderate (Grade 1 or 2) in severity. Many progeria patients have received continuous Zokinvy therapy for more than 10 years.

Zokinvy is FDA approved for the treatment of patients 12 months of age and older with a genetically confirmed diagnosis of Hutchinson-Gilford progeria syndrome or a processing-deficient progeroid laminopathy associated with either a heterozygous LMNA mutation with progerin-like protein accumulation or a homozygous or compound heterozygous ZMPSTE24 mutation.

In 2022, Eiger and AnGes entered into an exclusive distribution agreement for Zokinvy for the treatment of HGPS and PDPL indications in Japan. In March 2023, the Ministry of Health, Labour and Welfare designated Zokinvy as an orphan drug. Zokinvy was approved in the United States in 2020, and 30 European countries in 2022. Eiger will receive $500,000 as an approval milestone payment from AnGes.