Here comes the rare disease drug "meglumine chlorobenzoate soft capsule"

On February 6, the application for domestic listing of Pfizer chlorobenzoate meglumine soft capsule (acceptance No.: jxhs1900100) was changed to "issued document" in nmpa It is reported that the indication of this application is wild-type or hereditary transferrin amyloid cardiomyopathy (attr-cm), but no confirmation information from official sources was found It is expected that official information will be released soon Attr-cm is a rare and life-threatening disease caused by the instability of thyroxine protein (TTR) It is characterized by restrictive cardiomyopathy and progressive heart failure, and its core mechanism is the abnormal depolymerization of TTR protein TTR often exists in the form of tetramer After dissociation of unstable tetramer, it can lead to the aggregation of TTR with wrong folding and the deposition of amyloid fibril and amyloid protein in the myocardial interstitium, resulting in the hardening of the myocardium, and eventually progressive heart failure According to whether there is TTR gene mutation or not, attr-cm can be divided into wild type and heritability The genetic type attr-cm is due to TTR gene mutation, while the pathogenesis of wild type attr-cm is unclear, which may be related to oxidative emergency and degenerative change, and often occurs in men over 60 years old The diagnosis of attr-cm can only be obtained after the symptoms become serious, and once confirmed, the median survival time of patients is only 2-3.5 years According to statistics, there are about 100000 attr-cm patients in the United States, but only 1-2% of them are diagnosed Tafamidis meglumine (trade name vyndaqel) is a kind of TTR stabilizer developed by Pfizer By selectively binding with TTR, it can stabilize TTR and slow down its dissociation into monomers, thus delaying the production of attr amyloid protein deposition The drug was first approved by EMA in November 2011 for the treatment of attr-pn in adult patients with early symptomatic polyneuropathy to delay peripheral nerve injury In March 2019, vyndaqel was awarded the title of sakigake (leading type, pioneer type) drug by the Ministry of health, labor and welfare of Japan for the treatment of wild-type and variant attr-cm patients In May of the same year, vyndaqel was approved by the FDA for the treatment of adult wild-type or hereditary ttr-cm to reduce cardiovascular related mortality and hospitalization rate In December 2019, the EMA Committee on human medicinal products (CHMP) recommended vyndaqel for use in adult patients with wild-type or genetic attr-cm Chlorobenzoic acid is the first drug approved by FDA to treat attr-cm, and its annual sales have increased year by year since it was put on the market According to the data, vyndaqel's global sales continued to rise with the increase of approved countries, reaching US $180 million in 2018, an increase of 25.8% year on year In addition, in addition to vyndaqel, Pfizer's chlorobenzoic acid has another dosage form, namely, tafamidis (trade name vyndamax) At present, vyndamax and vyndaqel have been approved by FDA for the treatment of adult wild-type or genetic attr-cm in May 2019 However, it should be noted that the recommended dose of vyndaqel and vyndaqel is different in the treatment of attr-cm Among them, the recommended dose of vyndaqel is 80 mg (equivalent to four 20mg vyndaqel capsules), while the recommended dose of vyndamax is 61 Mg (i.e one vyndamax capsule) The development of this once-a-day dosage form is more convenient for patients to take and is conducive to improving patients' compliance In China, due to its breakthrough efficacy, chlorobenzoic acid was included in the "first batch of clinically urgent overseas new drugs list" in November 2018, and was listed and declared through the "technical guidelines for accepting overseas clinical trial data of drugs" and exempted from clinical trials in China In July 2019, CDE accepted the listing application of meglumine chlorbenzoate soft capsule After two months, CDE accepted the listing application of chlorbenzoate soft capsule (acceptance number is jxhs1900117), and the acceptance number is to be included in the priority review procedure.