Eiger is a biopharmaceutical company dedicated to the development and commercialization of targeted therapies to treat serious rare and ultra-rare diseases. Recently, the company announced that it has launched Zokinvy (lonafarnib) in the US market. The drug was approved by the US FDA in November 2020 for the treatment of progeria (Progeria, also known as: Hutchinson-Guilford Progeria Syndrome, HGPS) ) And Progeroid Laminopathies (PL) patients, reducing the risk of death. In clinical trials, Zokinvy treatment reduced mortality by 60% (p=0.0064) and prolonged life expectancy by 2.5 years. Many patients have used the drug for more than 10 years.
It is worth mentioning that Zokinvy is the world's first drug approved for the treatment of Progeria and Progeria-like Laminopathy (PL). At the same time as the approval, the FDA issued a rare pediatric disease priority review voucher (PRV) to Eiger to reward the company for its outstanding contributions in the field of progeria. On November 23, Eiger announced that it had sold this PRV for $95 million. According to the cooperation and supply agreement of the Progeria Research Foundation (PRF), Eiger retained 50% of the proceeds, or $47.5 million.
Eldon Mayer, Chief Commercial Officer of Eiger, said: “Zokinvy is a drug that has been proven to reduce the risk of death for patients with progeria. In order to fulfill our commitment to patients, we established Eiger OneCare, a comprehensive plan that includes professional care managers, Personalized support provided by reimbursement specialists, co-paid assistance for eligible patients, and other patient support services designed to help patients seeking treatment with Zokinvy."
In the United States, most of the identified Zokinvy eligible patients have received Zokinvy treatment through Eiger’s Global Expansion Access Program and have now joined Eiger OneCare, which will help smooth the transition to Zokinvy’s commercial supply.
In the United States, Zokinvy was approved through a priority review process, and the drug is currently undergoing accelerated evaluation by the European Medicines Agency (EMA). Previously, Zokinvy has been granted Orphan Drug Designation (ODD) for the treatment of Progeria and Progeria-like Laminopathy by the US FDA and EU EMA, and has been awarded Breakthrough Drug Designation (BTD) and Rare Pediatric Disease Designation (RPDD) by the FDA.
Progeria and Progeria-like Laminopathy (PL) is a unique, ultra-rare, hereditary premature aging disease that can cause premature aging of children and accelerate the death of young patients. Without treatment, children with progeria will die of heart disease, with an average age of death of 14.5 years. It is estimated that there are about 400 children with Progeria and 200 children with PL in the world, of which about 180 children and young adults have been confirmed by The Progeria Research Foundation, of which about 20 are in the United States and 23 are in the United States. Europe.
Zokinvy is a pioneering oral farnesyl transferase inhibitor (FTI) that blocks the farnesylation of progeria. The drug is a disease-modifying therapy that has significant survival benefits in children and young adults with Progeria. Among patients with progeria, Zokinvy reduced the mortality rate by 60% (p=0.0064) and increased the average survival time by 2.5 years. The most common adverse reactions are gastrointestinal reactions (vomiting, diarrhea, nausea), most of which are mild or moderate (grade 1 or 2). Many patients with Progeria have received Zokinvy treatment for more than 10 years.
Progeria (HGPS) is a rare and fatal genetic disease that accelerates aging in children. The disease is caused by a point mutation in the LMNA gene encoding lamin A (lamin A), which produces an abnormally farnesylated, toxic progerin. Lamin A is a part of the nuclear structure scaffold and plays an important role in nuclear structure and function. Children with progeria die from the same disease that affects millions of normally aging adults-arteriosclerosis, but the average age of death for children is 14.5 years. Progeria disease manifestations include severe hypoplasia, scleroderma-like skin, systemic lipodystrophy, hair loss, joint contractures, skeletal dysplasia, accelerated systemic atherosclerosis, decreased cardiovascular function, and stroke. It is estimated that there are about 400 children with Progeria worldwide.
Progeroid laminopathies are inherited from a series of mutations in the lamin A and/or Zmpste24 genes that accelerate aging. These mutations produce farnesylation that is different from progeroid laminopathies. protein. Although it does not produce progeria, mutations in these genes can cause disease manifestations that overlap but differ from those of progeria. In general, the incidence of Progeria-like lamina may be higher than Progeria on a global scale.
Lonafarnib is licensed by Eiger from Merck. The drug is an orally active inhibitor of farnesyltransferase with distinctive characteristics, which is in the late stage of development. Farnesyltransferase is called isoamylase. The process of diolefination is involved in the modification of proteins. Progeria is a farnesylated abnormal protein, which is believed to be unable to be cleaved, resulting in tight binding with the nuclear membrane, which leads to changes in nuclear membrane morphology and subsequent cell damage. Lonafarnib can block the farnesylation of progeria protein and has been proven to significantly reduce the risk of death in children with progeria.
Molecular structure of lonafarnib
In addition to treating progeria and progeria-like laminopathy, Eiger is also developing lonafarnib to treat hepatitis D virus (HDV) infection. At the end of December 2018, the FDA and EMA respectively granted lonafarnib the breakthrough drug designation (BTD) and the priority drug designation (PRIME) for the treatment of hepatitis D virus infection (HDV). Lonafarnib can inhibit the prenylation step of HDV replication in liver cells, blocking the virus life cycle during the virus assembly stage.
Data from a number of phase II clinical studies have confirmed the efficacy and safety of the lonafarnib-based regimen in the treatment of HDV infected patients. The data show that among the HDV-infected patients who have not previously received treatment (initial treatment), the lonafarnib-based regimen has achieved The combined primary endpoint of a reduction in HDV RNA levels ≥2 log10 and normalization of alanine aminotransferase (ALT) reflects an improvement in liver condition and virological response. Currently, the drug is in a pivotal HDV Phase III clinical study.
Hepatitis D is caused by HDV infection and is the most serious type of human viral hepatitis. Hepatitis D only occurs as a co-infection in individuals carrying the hepatitis B virus (HBV), causing liver diseases that are more serious than hepatitis B, and can accelerate liver fibrosis, liver cancer, and liver failure. Hepatitis D is a disease that seriously affects global human health. The disease may affect approximately 15-20 million people worldwide. The prevalence of hepatitis D varies in different regions of the world. According to reports, about 4.3%-5.7% of chronic hepatitis B virus carriers worldwide have HDV infection. In some regions, including parts of Outer Mongolia, China, Russia, Central Asia, Pakistan, Turkey, Africa, the Middle East and South America, the prevalence of HDV among chronic HBV infections is even higher. According to reports, Mongolia and Pakistan The prevalence of HDV among HBV infected persons is as high as 60%。