Merck’s odanacatib shows promise in cancer
pharmafile | May 30, 2008 | News story | Research and Development, Sales and Marketing |
Merck's odanacatib (MK-0822) has shown promising results in phase II trials in treating breast cancer which has spread to bones.
The investigational cathepsin K inhibitor reduced the breakdown and rebuilding of bone in women with breast cancer who also had metastatic bone disease – which occurs when cells from the primary tumour move to the bone, the most common site for the cancer to spread.
Around three-quarters of women with advanced breast cancer develop bone metastases and two-thirds of them experience serious complications such as excruciating pain, fractures or nerve damage including spinal cord compression.
The cathepsin K enzyme helps break down bone protein, a process which tumour cells speed up, resulting in further tumour growth and bone destruction.
Inhibiting the enzyme should slow bone destruction and the study showed once-daily oral odanacatib 5-mg reduced the level of urinary N-telopeptide (uNTx), a commonly-used marker of bone breakdown, by 77% from baseline levels over four weeks.
The results, to be presented at the American Society of Clinical Oncology annual meeting, were seen as early as day seven. Decreases in other markers of bone turnover, including bone resorption urinary deoxpyridinoline (uDPD) and bone formation serum bone-specific alkaline phosphatase (sBSAP) were also observed, as was an increase in serum crosslinked C-terminal peptide (s1CTP), a marker of cathepsin K activity.
"Bone metastases represent a frequent and serious complication for patients with breast cancer," said Christopher Wynne, study investigator and clinical oncologist at Christchurch Clinical Studies Trust in New Zealand.
"These findings show that odanacatib reduced several well characterized biochemical markers of bone turnover in cancer patients with metastasis to bone, indicating this investigational medicine has the potential to slow the accelerated rate of bone destruction associated with bone metastases."
Antonio Lombardi, senior director of Merck Research Laboratories, commented: "This is the first study to evaluate odanacatib in cancer patients. Based on these findings, larger Phase III studies using the 5-mg daily dose of odanacatib are being planned for patients with breast and prostate cancer."
A phase III trial evaluating odanacatib for osteoporosis in postmenopausal women also is underway. If successful, the drug could challenge treatments such as GSK/Roche's osteoporosis treatment Boniva/Bonviva (ibandronate).
