India: USFDA Approves First Therapy For Rare, Inherited Form Of Rickets - X-Linked Hypophosphatemia

On April 17, 2018, the United States Food and Drug Administration (US-FDA) approved Crysvita (burosumab), the first drug approved to treat adults and children aged 1 year and older with x-linked hypophosphatemia (XLH), a rare, inherited form of rickets51. XLH causes low levels of phosphorus in the blood. It leads to impaired bone growth and development in children and adolescents and problems with bone mineralization throughout a patient's life.

The FDA granted approval of Crysvita to Ultragenyx Pharmaceutical Inc., a biopharmaceutical company focused on the development of novel products for rare and ultra-rare diseases.

The safety and efficacy of Crysvita were studied in four clinical trials. In the placebo-controlled trial, 94 percent of adults receiving Crysvita once a month achieved normal phosphorus levels compared to 8 percent of those receiving placebo. In children, 94 - 100% of patients treated with Crysvita every two weeks, achieved normal phosphorus levels. In both children and adults, X-ray findings associated with XLH improved with Crysvita therapy. Comparison of the results to a natural history cohort also provided support for the effectiveness of Crysvita.

About X-Linked Hypophosphatemia (XLH)                                                                             

According to the National Institute of Health (NIH) of the United States, X-linked hypophosphatemia (XLH) is an inherited disorder characterized by low levels of phosphate in the blood. Phosphate levels are low because phosphate is abnormally processed in the kidneys, which causes a loss of phosphate in the urine (phosphate wasting) and leads to soft, weak bones (rickets). XLH is usually diagnosed in childhood. Features include bowed or bent legs, short stature, bone pain, and severe dental pain52.

XLH is caused by mutations in the PHEX gene on the X chromosome, and inheritance is X-linked dominant. Treatment generally involves supplements of phosphate and high-dose calcitriol (the active form of Vitamin D), and may also include growth hormones, corrective surgery, and dental treatment. The long-term outlook varies depending on severity and whether complications arise. While some adults with XLH may have minimal medical problems, others may experience persistent discomfort or complications.

XLH is a serious disease affecting approximately 3,000 children and 12,000 adults in the United States. Most children with XLH experience bowed or bent legs, short stature, bone pain and severe dental pain. Some adults with XLH experience persistent discomfort or complications, such as joint pain, impaired mobility, tooth abscesses and hearing loss.

Crysvita is designed to bind the excess FGF23 in these patients, normalizing phosphorus levels, improving bone mineralization, improving rickets in children and healing fractures in adults.

About Crysvita                                                                                                                      

Crysvita is a recombinant fully human monoclonal IgG1 antibody, discovered by Kyowa Hakko Kirin, against the phosphaturic hormone fibroblast growth factor 23 (FGF23). FGF23 is a hormone that reduces serum levels of phosphorus and active vitamin D by regulating phosphate excretion and active vitamin D production by the kidney. Phosphate wasting in XLH is caused by excessive levels and activity of FGF23. Crysvita is designed to bind to and thereby inhibit the biological activity of FGF23. By blocking excess FGF23 in patients, Crysvita is intended to increase phosphate reabsorption from the kidney and increase the production of active vitamin D, which enhances intestinal absorption of phosphate and calcium53.

Earlier, Crysvita was granted Breakthrough Therapy designation, under which the FDA provides intensive guidance to the company on efficient drug development, and expedites its review of drugs that are intended to treat serious conditions where clinical evidence shows the drug may represent a substantial improvement over other available therapies. Crysvita also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

The sponsor also received a Rare Pediatric Disease Priority Review Voucher. According to the Federal Food, Drug, and Cosmetic Act (FD&C Act), FDA awards priority review vouchers to sponsors of rare pediatric disease product applications that meet certain criteria. Under this program, a sponsor who receives an approval for a drug or biologic for a "rare pediatric disease" may qualify for a voucher that can be redeemed to receive a priority review of a subsequent marketing application for a different product54.. This is only the 14th Rare Pediatric Disease Priority Review Voucher issued by the FDA since the program began.

Footnotes

51 https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm604810.htm

52 https://rarediseases.info.nih.gov/diseases/12943/x-linked-hypophosphatemia

53 http://ir.ultragenyx.com/news-releases/news-release-details/ultragenyx-and-kyowa-kirin-announce-fda-approval-crysvitar

54 https://www.fda.gov/ForIndustry/DevelopingProductsforRareDiseasesConditions/RarePediatricDiseasePriorityVoucherProgram/default.htm

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