Celera (Rockville, Maryland), an Applera Corp business, announced a clinical milestone payment of $2 million from Merck & Co, Inc, under the cathepsin K inhibitor collaboration agreement between the companies. This payment recognizes Merck's advancement of odanacatib (formerly MK-0822), an orally available highly selective inhibitor of the cathepsin K enzyme, to a phase III clinical trial as a potential treatment for osteoporosis. If this candidate or others developed under the cathepsin K collaboration are advanced to commercialization, Celera will receive from Merck additional milestone payments and, potentially, will also receive royalties on net sales.

Celera's multiyear research collaboration with Merck to develop small molecule inhibitors of cathepsin K began in November 1996 and was extended in December 2001, whereby Celera continued to provide a series of candidate compounds to support Merck's research programs. Celera completed its collaboration in February 2003, after which time Merck has been responsible for further research and development related to collaboration compounds.

Merck recently announced 12-month results from a multicenter, double-blind, randomized, placebo-controlled phase IIb study with odanacatib. The drug, compared with placebo, demonstrated dose-dependent increases in bone mineral density (BMD) at key fracture sites and reduced bone turnover in postmenopausal women with low BMD when given at doses of 10, 25, or 50 mg. Compared with baseline values, treatment with odanacatib 50 mg administered orally once-weekly (N = 77) increased by 3.4% lumbar spine (LS) BMD at 12 months, the primary study endpoint, whereas treatment with placebo (N = 81) decreased LS BMD by 0.1%. Dose-related increases in BMD at other measured skeletal sites including total hip, femoral neck, and hip trochanter were seen with the 10, 25, and 50 mg doses of odanacatib compared with baseline, but not with the 3 mg dose or placebo. Increases in total body and distal forearm BMD were not observed at the four odanacatib doses studied.

The study also explored the reduction in bone turnover from baseline as measured by sCTx (serum C-telopeptides of Type 1 collagen), a biochemical marker of the rate of bone removal. Results with various dosages of odanacatib showed bone turnover was 57% at 50 mg, 36% at 25 mg, and 22% at 10 mg. There were no observed results with either odanacatib 3 mg or placebo. Odanacatib 50 mg minimally reduced s-BSAP (bone specific alkaline phosphatase), a measure of new bone being formed, by 18%. Measures of s-CTX and s-BSAP for placebo were -0.6% and -3%, respectively.

Discontinuation rates due to an adverse event (AE) for the four odanacatib doses were similar to placebo.

The cathepsin K enzyme is believed to play a role in both osteoclastic bone resorption and in degrading the protein component of bone. The inhibition of the cathespin K is a mechanism of action different from that of currently approved osteoporosis treatments such as bisphosphonates.


—A. Techman