FDA Approves the first genetic rickets drug

Source: US and Chinese drug sources April 18, 2018 FDA approved the FGF23 antibody burosumab (trade name: crysvita ®) jointly developed by ultragenyx (rare) / Kyowa Kirin for the treatment of X-linked low phosphorus rickets (XLH) over one year old This is the first XLH drug to be launched in the United States, and the second first new drug to be launched by rare within six months after mepsevii Crysvita has previously obtained FDA's breakthrough drug status and priority approval qualification, so are will receive another priority review Certificate (PRV), because the PRV obtained by mepsevii has been sold to Novartis for $130 million Crysvita sells for $200000 a year, with an estimated peak sales of $1 billion XLH is a rare disorder of phosphorus metabolism caused by a gene mutation called PHEX It is estimated that 12000 XLH patients in the United States have bone deformation and delayed development Calcium and phosphorus are important inorganic salts in the process of life Their metabolism is controlled by many organs, such as bone, kidney, gastrointestinal and so on Parathyroid hormone and activated vitamin D are the main regulatory hormones, but for many years, scientists have speculated that there is another kind of hormone involved in the regulation of phosphorus and calcium metabolism, and named it phosphatonin In 2001, it was found that FGF23 (the 23rd member), a new member of the fibroblast growth factor (FGF) family, was one of the latent phosphatonins for many years Although several similar hormones were found later, FGF23 is still the most important phosphatonin FGF23 is mainly secreted by bone, which inhibits the reabsorption of phosphorus by kidney and the synthesis of active vitamin D PHEX mutation induced abnormal secretion of FGF23, which resulted in low serum phosphorus concentration XLH is different from other rickets caused by phosphorus metabolism because of the poor effect of vitamin D treatment, while phosphorus supplements are not only inconvenient to adjust the dosage frequently, but also not to interfere with the disease itself Crysvita combined with FGF23 and inhibited its function, which was closer to the treatment In two clinical trials in children, crysvita improved bone, increased blood phosphorus concentration, decreased alkaline phosphatase and improved development In two adult clinical trials, crysvita improved osteoporosis, the proportion of patients with normal blood phosphorus was significantly higher than that of placebo, and helped fracture recovery, but the failure to alleviate the pain caused some investors a bit of confusion Rare is a young small company founded in 2010 and listed in 2014 In addition to the two drugs already listed, there are two or three post phase II clinical assets Rare focuses on rare diseases with clear biological mechanism, and its products are mostly substitutes of endogenous substances (such as enzymes and hormones) or gene therapy I personally think this is the most direct treatment for the disease, of course, this disease is usually a rare disease with a limited number of people Balancing R & D risk and market return is a highly difficult technical activity The other extreme is the R & D black hole with huge return but complex mechanism like ad It took only 17 years from the discovery of target FGF23 to the launch of crysvita new drug, which is a great achievement, especially for a young enterprise like rare with limited resources Although some people think that the therapeutic effect of crysvita is not worth the high price, the R & D efficiency of two pioneering new drugs that are launched in the market in the past 8 years to solve the high unmet medical demand is still worth learning from the industry.