Cytochroma Inc. Initiates Phase 3 Study of CTAP101 Capsules in Chronic Kidney Disease Patients

MARKHAM, ON, Sept. 20, 2012 /PRNewswire/ - Cytochroma today announced the initiation of a phase 3 study of CTAP101 capsules ("CTAP101 Capsules") in patients with secondary hyperparathyroidism (SHPT), stage 3 or 4 chronic kidney disease (CKD) and vitamin D insufficiency. The newly initiated trial is the first of two identical randomized, double-blind, placebo controlled, multi-site studies intended to establish the safety and efficacy of CTAP101 Capsules as a new treatment for SHPT in the targeted population. The endpoints of both studies, which will be conducted in parallel, include vitamin D status, adverse events, physical and clinical laboratory assessments, and changes in serum calcium, serum phosphorus and plasma intact parathyroid hormone (PTH).

"Secondary hyperparathyroidism develops in CKD patients due to vitamin D insufficiency or declining kidney function," explained Joel Z. Melnick, M.D., Cytochroma's Vice President, Clinical Research and Development. "Most CKD patients have insufficient stores of vitamin D due to the abnormal upregulation of CYP24, an enzyme which specifically destroys vitamin D and its metabolites. Many recent studies in CKD patients have demonstrated that over-the-counter and prescription vitamin D supplements cannot reliably raise blood vitamin D prohormone levels or effectively treat SHPT. In contrast, our phase 2b trial has demonstrated that CTAP101 Capsules effectively and safely treat both SHPT and the underlying vitamin D insufficiency."

The ongoing phase 3 trial will involve 210 patients recruited from approximately 30 sites in the United States (US). These patients will be stratified by CKD stage and randomized in a 2:1 fashion to receive six months of treatment with either CTAP101 Capsules or matching placebo. Dosing with CTAP101 Capsules will start at 30 mcg/day and be titrated, as necessary, to achieve the desired drug concentration in the blood and the targeted reduction in plasma PTH.

"CTAP101 Capsules are being developed as a much needed and safer alternative to currently used activated vitamin D hormones," commented Dr. David Bushinsky, Chief of Nephrology at the University of Rochester. "Activated vitamin D hormone therapy is problematic in CKD patients with secondary hyperparathyroidism arising primarily from vitamin D insufficiency since it further stimulates catabolism of the available vitamin D stores and is often associated with hypercalcemia, a side effect linked to vascular calcification."

The phase 3 program will be funded, in part, by committed financings of nearly $CDN 32 million of which the first two stages closed earlier this year. The lead investors in the financings were Covington Fund II (Toronto) and Business Development Bank of Canada (Montreal). Participating investors included the Bombardier Trust (Canada) Funds (Montreal), Caisse de dépôt et placement du Québec (Québec), Comerica Bank (Toronto), GrowthWorks (Toronto), MaRS Investment Accelerator Fund (Toronto), Partners Group (Zug), Roseway Capital Sarl (Luxembourg) and VentureLink Innovation Fund (Toronto).

"Covington is delighted to support the phase 3 development of CTAP101 Capsules," stated Ms. Lily Lam, VP Investments, Covington and a director of Cytochroma. "Speaking on behalf of all participants in these financings, we view CTAP101 Capsules as a well-advanced and low risk product candidate with high commercial prospects under rapid development by an experienced management team."

The two identical pivotal Phase 3 trials are covered by a Special Protocol Assessment granted by the US Food and Drug Administration (FDA) on August 30, 2012.

About CTAP101 Capsules

The product, CTAP101 Capsules, is a first-in-class vitamin D prohormone treatment being developed for elevated PTH secretion (SHPT) in 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 the product by the kidney is tightly regulated, preventing excessive elevation of serum calcium and related side effects which encumber vitamin D hormone therapies and promote vascular and renal calcification.

About Chronic Kidney Disease

CKD is a condition characterized by a progressive decline in kidney function. The kidney is normally responsible for excreting waste and excess water from the body, and for regulating various hormones. CKD is classified in five different stages - mild (stage 1) to severe (stage 5) disease - as measured by the kidney's glomerular filtration rate. According to the National Kidney Foundation, CKD afflicts over 26 million people in the US, including more than eight million patients with moderate (stages 3 and 4) and severe (stage 5) forms of CKD. In stage 5 CKD, kidney function is minimal to absent and patients require regular dialysis or a kidney transplant for survival.

About Vitamin D Insufficiency

Vitamin D insufficiency is a condition in which the body has low vitamin D stores, characterized by inadequate blood levels of vitamin D prohormones, collectively known as 25-hydroxyvitamin D. An estimated 70-90% of CKD patients have vitamin D insufficiency, which can lead to SHPT and resultant debilitating bone diseases.

About Secondary Hyperparathyroidism (SHPT)

SHPT is a condition commonly associated with CKD in which the parathyroid glands secrete excessive amounts of PTH. SHPT arises as a result of vitamin D insufficiency or impaired kidney function that prevents sufficient production of vitamin D hormones to properly regulate calcium and phosphorus metabolism, and PTH secretion. Prolonged elevation of blood PTH causes excessive calcium and phosphorus to be released from bone, leading to elevated serum calcium and phosphorus, softening of the bones (osteomalacia) and calcification of vascular and renal tissues. SHPT affects 40-60% of patients with moderate CKD and approximately 90% of patients with severe CKD.

About Cytochroma

Cytochroma is a clinical-stage specialty pharmaceutical company focused on developing and commercializing proprietary products to treat and prevent the clinical consequences of vitamin D insufficiency and SHPT associated with CKD. The Company specializes in developing new vitamin D therapies which are designed to safely and effectively treat patients with stage 3, 4 or 5 CKD. Cytochroma also has a portfolio CYP24 and phosphate-uptake inhibitors in early stages of development.

SOURCE Cytochroma