business agreement handshakeVifor Fresenius Medical Care Renal Pharma (VFMCRP), a common company of Galenica and Fresenius Medical Care, and OPKO Health, have entered into a collaboration and license agreement for the development and commercialization of RAYALDEE in Europe, Canada, Mexico, Australia, South Korea and certain other international markets for the treatment of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) and vitamin D insufficiency.

Under the terms of the agreement, the parties will also collaborate to develop and commercialize RAYALDEE for the treatment of SHPT in dialysis patients, and OPKO has granted VFMCRP an option to acquire rights to the US market for treatment of dialysis patients.

“Vifor Fresenius Medical Care Renal Pharma is a leader in chronic kidney disease and we believe they are the ideal partner to bring RAYALDEE to patients across Europe and other territories,” said Phillip Frost, MD, Chairman and Chief Executive Officer of OPKO. “We believe further developing RAYALDEE for dialysis patients is an important additional step in the care of chronic kidney disease patients,” Dr Frost continued.

“Managing bone and mineral disorders in CKD patients remains a challenge for physicians despite the treatment options already available to them. The clinical data for RAYALDEE show promising safety and efficacy and we strongly believe that once approved, RAYALDEE will become a cornerstone therapy to better address this key co-morbidity and improve the well-being of chronic kidney disease patients,” said Stefan Schulze, Chief Executive Officer of VFMCRP.

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. VFMCRP has entered into an exclusive license agreement with OPKO to co-develop and commercialize 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).

Under the agreement, VFMCRP will make an upfront payment to OPKO of $50 million, plus up to an additional $52 million in regulatory and launch milestones, and $180 million in sales-based milestones. In addition, VFMCRP will pay OPKO tiered, double-digit royalties on sales of the product. In the event VFMCRP exercises its option for rights to the US dialysis market, VFMCRP will pay OPKO additional commercial-based milestones, as well as double-digit royalties. 

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 25 March 2016, as a result of an FDA field inspection initiated on 14 March 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 22 April 2016. The new Prescription Drug User Fee Act (PDUFA) date is 22 October 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’s ability to correct vitamin D insufficiency and treat SHPT without meaningfully increasing serum calcium or phosphorus levels.