Date: 2014-09-23
Type of information: Results
phase: 3
Announcement: results
Company: OPKO Health (USA - FL)
Product: Rayaldee™ ( calcifediol - vitamin D prohormone)
Action
mechanism: Rayaldee™ is a first-in-class oral vitamin D prohormone treatment being developed for secondary hyperparathyroidism in stage 3 and 4 CKD patients with 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 encumber current vitamin D hormone therapies and promote vascular and renal calcification. Once approved, Rayaldee™ is expected to address an approximate 4 million CKD stage 3 and 4 patients in the U.S. and many more, elsewhere, with SHPT and vitamin D insufficiency.
Disease: secondary hyperparathyroidism (SHPT) in patients with stage 3 or 4 chronic kidney disease (CKD) and vitamin D insufficiency
Therapeutic area: Endocrine diseases - Hormonal diseases- Kidney diseases - Renal diseases
Country: USA
Trial details:
Latest
news: * On September 23, 2014, OPKO Health 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 FDA in August 2012. This trial involved 216 adult patients recruited from 38 sites throughout the U.S. 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. * On August 11, 2014, OPKO Health announced successful top-line results from the first pivotal phase 3 trial of Rayaldee™. This trial is one 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 (SPA) established with the FDA in August 2012. This trial involved 213 adult patients recruited from 39 sites throughout the U.S. 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.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 (p < 0.001) 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. Top-line data from the second, identical pivotal phase 3 trial are expected to be available in September 2014 . Patients completing the two pivotal trials are being treated, at their election, for an additional 6 months with Rayaldee® during an ongoing open-label extension study. Enrollment in this extension study surpassed the targeted level of 270 patients by May 2014 and 141 patients have completed participation. A New Drug Application (NDA) submission to the FDA is on track for the end of 2014.
A New Drug Application submission to the FDA is planned for the end of 2014.
