Patients who have rickets experience a softening and weakening of their bones traced to a vitamin deficiency. In a rare, inherited form of the disease, vitamin D supplements don’t work.
Ultragenyx (NASDAQ: RARE) has received FDA approval for a drug to treat patients who have this form of the disease, called X-linked hypophosphatemia (XLH). The Novato, CA-based company said Tuesday that the regulatory approval for its drug, burosumab (Crysvita), covers adults as well as children over the age of 1. The FDA’s nod, which came following a priority review given to drugs developed to offer significant improvement in the treatment of a serious condition, gives Ulgragenyx its second rare disease drug approval in the past six months.
XLH is an ultra-rare disease that affects both males and females. Ultragenyx estimates it affects only about 3,000 children and 9,000 adults in the U.S. Those patients, or their insurance companies, will pay $200,000 per adult and approximately $160,000 per child for one year of treatment. The children’s price can vary because the amount of the injectable drug given to patients is based on weight, chief financial officer Shalini Sharp said on a conference call to discuss the approval. She added that factors the company considered in price setting included the severity of the disease, the drug’s ability to treat its underlying cause, and the pricing of other rare disease drugs that serve similarly sized patient populations.
Vitamin D helps the body absorb calcium and phosphate, which are important to bone health. In XLH, the kidneys have problems handling phosphate and metabolizing vitamin D, according to the National Organization for Rare Disorders. The abnormally low levels of phosphate in the blood, called hypophosphatemia, is often inherited as an X-linked trait, hence the name of the disorder.
Patients who have XLH experience an excess production of a hormone called FGF23. NORD says research has shown that this hormone causes the kidneys to excrete excess amounts of phosphate in the urine, a process called renal phosphate wasting. The low levels of phosphate in the blood can cause rickets, which can then lead to bone deformities, decreased height, and a greater risk of fractures.
Ultragenyx says burosumab was developed to regulate the kidneys’ phosphate excretion and vitamin D production. It’s an antibody drug that binds to excess FGF23, which in turn is meant to restore phosphates to normal levels. In Phase 2 results released last year from a 54-week open-label study enrolling 52 children, Ultragenyx reported that treatment with the drug improved rickets, reduced the activity of enzymes that remove phosphates, increased phosphate levels, and increased growth. Ultragenyx says side effects in children include skin reactions at the site of the injection, headache, vomiting, and fever.
In adults, Ultragenyx tested the drug in a 23-week, randomized, double-blind, and placebo-controlled study enrolling 134 patients. The company reported that treatment with its drug increased phosphate levels in the blood, and that patients had a higher rate of complete healing of active fractures, compared to those in the placebo group. Side effects observed in the adult studies included back pain, headache, dizziness, and constipation.
Burosumab was discovered by Japan-based Kyowa Hakko Kirin (KHK). In 2013, Ultragenyx entered a licensing and collaboration agreement with KHK. The deal calls for the partners to share development and commercialization of the drug in the U.S., Canada, and Europe. Ultragenyx also holds the rights to develop and commercialize the drug in Latin America.
The FDA approval of the Ultragenyx drug comes with a priority review voucher for a rare pediatric disease. Ultragenyx can apply this voucher to the review of another drug application that would not otherwise qualify for priority review. But some companies view these vouchers as assets that can be bought and sold. Ultragenyx was awarded a priority review voucher in November with the FDA approval of vestronidase alfa (Mepsevii), an enzyme replacement therapy and the first approved treatment for a lysosomal storage disorder that is sometimes called Sly syndrome. A month later, Ultragenyx sold that voucher to Novartis (NYSE: NVS) for $130 million.