SHPT is a common disorder in CKD patients triggered by vitamin D insufficiency, which can cause reduced vitamin D hormone production, decreased intestinal absorption of dietary calcium, increased secretion of parathyroid hormone (PTH), and metabolic bone disease. Using current treatment options, most patients underachieve control of both vitamin D insufficiency and SHPT, leading to a range of bone and mineral disorders.
Rayaldee is an oral vitamin D prohormone treatment in a modified release capsule being developed by OPKO. Vifor has entered into an exclusive license agreement with OPKO to co-develop and commercialise Rayaldee in leading markets around the world, including Europe (except Russia), Canada, Mexico, Australia and South Korea. OPKO retains all rights in the US, Latin America (excluding Mexico), Russia, China, Taiwan and Japan. The two companies will also collaborate to prepare the Marketing Authorization Application (MAA) submission to the European Medicines Agency (EMA).
OPKO submitted a New Drug Application (NDA) for Rayaldee to the US Food and Drug Administration (FDA) in 2015 for the treatment of SHPT in patients with stage 3 or 4 CKD and vitamin D insufficiency. On 29 March 2016, the FDA indicated in a Complete Response Letter (CRL) that observations of deficiencies at OPKO's third-party contract manufacturer were issued on March 25, 2016, as a result of an FDA field inspection initiated on March 14, 2016. The observations were not specific to Rayaldee manufacturing. The CRL did not cite any safety, efficacy or labelling issues with regard to Rayaldee, nor did it request that additional studies be conducted prior to FDA approval. OPKO subsequently resubmitted its NDA to the FDA, and the FDA accepted OPKO's resubmission on April 22, 2016. The new Prescription Drug User Fee Act (PDUFA) date is October 22, 2016.
The NDA is supported by data from three randomized, double-blind, placebo-controlled studies and one open label extension study conducted in the targeted patient population at 105 US sites.
These studies met all primary efficacy and safety endpoints, confirming the anticipated product profile of Rayaldee ability to correct vitamin D insufficiency and treat SHPT without meaningfully increasing serum calcium or phosphorus levels.