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.
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.