OPKO Health, Inc., a multinational biopharmaceutical and diagnostics company,  announced successful top-line results from the second and final pivotal phase 3 trial of Rayaldee. This trial is the second of two identical randomized, double-blind, placebo-controlled, multi-site studies intended to establish the safety and efficacy of Rayaldee as a new treatment for secondary hyperparathyroidism (SHPT) in patients with stage 3 or 4 chronic kidney disease (CKD) and vitamin D insufficiency. Both trials are the subject of a Special Protocol Assessment established with the United States (US) Food and Drug Administration (FDA) in August 2012.

"Top-line data from this second study confirmed that Rayaldee effectively controls secondary hyperparathyroidism in patients with stage 3 or 4 chronic kidney disease by correcting vitamin D insufficiency," stated Joel Z. Melnick, M.D., vice president of clinical research and development for OPKO's Renal Division. "As with the first trial, Rayaldee was equally effective in both disease stages, indicating that this new therapy is appropriate even for patients with minimal functioning kidney mass."

This trial involved 216 adult patients recruited from 38 sites throughout the US. Patients were stratified by CKD stage and randomized in a 2:1 fashion to receive six months of treatment with either Rayaldee or placebo. On enrollment, all patients exhibited vitamin D insufficiency which was corrected in 96% of patients treated with Rayaldee vs. 8% of patients treated with placebo.

The completed trial successfully met all primary efficacy and safety endpoints. The primary efficacy endpoint was a responder analysis in which "responder" was defined as any treated subject who demonstrated an average 30% decrease in plasma parathyroid hormone (PTH) from pre-treatment baseline during the last six weeks of the treatment period. A significantly higher response rate was observed with Rayaldee which steadily increased with treatment duration. The response rate with Rayaldee was similar in CKD stages 3 and 4. Safety and tolerability data were comparable in both treatment groups.

Patients who completed the two pivotal trials are being treated, at their election, for an additional 6 months with Rayaldee during an open-label extension study. Enrollment in this extension study is complete at 298 patients, of which 180 (69%) patients have completed participation.

"The data from the two pivotal phase 3 studies, when combined with the available data from the ongoing open-label extension study, provide a clear picture of Rayaldee's efficacy during longer-term administration," commented Dr. Charles W. Bishop, Ph.D., CEO of OPKO's Renal Division. "The gradual but progressive PTH lowering observed during 6 months of treatment in the pivotal trials is continuing during 6 additional months of treatment in the extension study, allowing PTH levels to return to the normal range in a significant proportion of patients."

"Gradual reduction of elevated PTH towards the normal range is likely to become the new treatment goal for predialysis patients whose secondary hyperparathyroidism has not become firmly established," stated Stuart M. Sprague, DO, Chief, Division of Nephrology and Hypertension, NorthShore University Health System - University of Chicago, Pritzker School of Medicine. "Currently, these patients are treated with high doses of nutritional vitamin D, but fewer than 50% show an adequate response. Inadequate correction of vitamin D insufficiency with nutritional vitamin D allows secondary hyperparathyroidism to become established and less responsive to treatment. The phase 3 data with Rayaldee show that this product is highly effective in correcting vitamin D insufficiency, allowing more reliable treatment of these patients."

"OPKO is committed to improving the care of patients with chronic kidney disease by developing safer and more effective therapies for secondary hyperparathyroidism than those available today," commented Phillip Frost, M.D., chairman and CEO of OPKO Health. "Rayaldee provides an excellent solution to the problem of secondary hyperparathyroidism associated with vitamin D insufficiency for the 20 million pre-dialysis CKD patients in the U.S. and many more elsewhere."

A New Drug Application submission to the FDA is planned for the end of 2014.

Rayaldee is a first-in-class oral vitamin D prohormone treatment being developed for SHPT in patients with stage 3 or 4 CKD and vitamin D insufficiency. It has a proprietary modified-release formulation designed to gradually and reliably raise serum total 25-hydroxyvitamin D (prohormone) concentrations to targeted levels (at least 30 ng/mL) while avoiding upregulation of CYP24, a cytochrome P-450 enzyme that reduces the PTH-lowering potency of current vitamin D supplements. Activation of calcifediol, the active ingredient in Rayaldee, by the kidney is tightly regulated, preventing excessive elevation of serum calcium and related side effects which limit the value of current vitamin D hormone therapies by promoting vascular and renal calcification. Rayaldee is expected to address the approximately 8 million patients in the US, and many more elsewhere, with stage 3 or 4 CKD, SHPT and vitamin D insufficiency.

The Special Protocol Assessment provided a mechanism for the FDA and OPKO to reach agreement on the design, size, execution and analysis of the two pivotal phase 3 trials with Rayaldee. The FDA agreed that the design and planned analysis of these studies adequately addressed the objectives necessary to support an NDA submission.