Date: 2016-06-21
Type of information: Granting of a Market Authorisation in the US
Product name: Rayaldee®
Compound: calcifediol - vitamin D prohormone
Therapeutic area: Kidney diseases - Renal diseases - Metabolic diseases
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.
Company: Opko Health (USA - Fl)
Disease: prevention and treatment of secondary hyperparathyroidism (SHPT) in patients with stage 3 or 4 chronic kidney disease (CKD) and vitamin D insufficiency
Latest news: * On June 21, 2016, OPKO Health announced that the FDA has approved Rayaldee® (calcifediol) extended release capsules for the treatment of secondary hyperparathyroidism (SHPT) in adults with stage 3 or 4 chronic kidney disease (CKD) and serum total 25-hydroxyvitamin D levels less than 30 ng/mL. U.S. launch is planned for 2H 2016. Rayaldee® is a patented extended release product containing 30 mcg of a prohormone called calcifediol (25-hydroxyvitamin D3). Results from two 26 week placebo controlled, double blind phase 3 trials demonstrated that a larger proportion of stage 3 or 4 CKD patients with SHPT and vitamin D insufficiency achieved ?30% reductions in plasma intact parathyroid hormone (iPTH) when treated with Rayaldee® than with placebo. Vitamin D insufficiency was corrected in more than 80% of the patients receiving Rayaldee® compared with less than 7% of subjects receiving placebo. Mean serum calcium and phosphorus levels increased by 0.1 mg/dL during Rayaldee® treatment compared to placebo treatment, but these changes were deemed clinically irrelevant. No differences in Rayaldee® 's efficacy or safety were observed between patients with stage 3 CKD or stage 4 CKD. * On April 27, 2016, OPKO Health announced the FDA has accepted OPKO's resubmission on April 22, 2016 of the New Drug Application (NDA) for Rayaldee® (calcifediol) for the treatment of secondary hyperparathyroidism (SHPT) in patients with stage 3 or 4 chronic kidney disease (CKD) and vitamin D insufficiency. * On March 30, 2016, OPKO Health announced that the FDA has issued a complete response letter (CRL) to the Company's New Drug Application (NDA) for Rayaldee® (calcifediol) as a treatment for secondary hyperparathyroidism (SHPT) in patients with stage 3 or 4 chronic kidney disease (CKD) and vitamin D insufficiency. The FDA indicated in the 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 labeling issues with regard to Rayaldee®, nor did it request any additional studies to be conducted prior to FDA approval. The Company's third-party manufacturer has committed to respond promptly to the FDA's observations to ensure early resolution. * On July 29, 2015, Opko Health announced that the FDA has accepted for review Opko's New Drug Application (NDA) for calcifediol modified-release capsules (Rayaldee™). In the NDA, Opko seeks approval of Rayaldee™ for the prevention and treatment of secondary hyperparathyroidism (SHPT) in patients with stage 3 or 4 chronic kidney disease (CKD) and vitamin D insufficiency. Opko expects written notification of NDA acceptance along with the Prescription Drug User Fee Act (PDUFA) date in the FDA's 74-Day letter, which the Company expects to receive by mid-August 2015. 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 a total of 105 U.S. sites. These studies met all primary efficacy and safety endpoints, as previously announced. * On June 9, 2015, Opko Health announced that it has submitted a New Drug Application (NDA) for oral Rayaldee® to the FDA. The NDA requests marketing approval for Rayaldee® for the prevention and treatment of secondary hyperparathyroidism (SHPT) in patients with stage 3 or 4 chronic kidney disease (CKD) and vitamin D insufficiency. The Rayaldee® application is supported by positive data from three randomized, double-blind, placebo-controlled studies and one open-label extension study conducted in the targeted patient population at a total of 105 U.S. sites. These studies met all primary efficacy and safety endpoints, as previously announced.
OPKO resubmitted the NDA following receipt of a complete response letter (CRL) from the FDA on March 29, 2016 , in which the FDA indicated the NDA could not be approved due to deficiencies observed during a facility inspection of OPKO's third party manufacturer (see below). A six month review period has been assigned for the resubmitted NDA, and the new Prescription Drug User Fee Act (PDUFA) date will be October 22, 2016 .
Patents:
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2016-06-21
UE authorization:
Favourable opinion UE:
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: OTC status: Other news:
