’s focus on innovation will overcome issues with top-line growth, according to Sean Harper, Ph.D., the firm’s CMO. Besides all eyes being focused on gaining approval for denosumab, the company is making sure it has a solid pipeline.
Since about 2000, Amgen has tripled its clinical program, according to Dr. Harper. Its focus on integrating biomarker research with drug R&D has helped move only the best candidates into Phase I studies, he adds. The company now has 28 different compounds in Phase I, II, and III trials, with about five undergoing development in multiple indications.
“The Phase I and Phase II pipeline is the most exciting it’s ever been,” remarks Dr. Harper. His picks include AMG 655, AMG 386, and Sclerostin Ab. AMG 655 and AMG 386 are both in Phase II and are being developed as anticancer agents. AMG 386 is a peptibody that binds to and inhibits angiopoietin 1 and 2. AMG 655 is a fully human mAb agonist that targets death receptor 5 and induces apoptosis in sensitive tumor cells.
Sclerostin Ab is a humanized antibody that targets sclerostin, a protein secreted by bone cells as a negative regulator of bone formation. It is in Phase I and is being developed with UCB for bone-related conditions. Phase II trials with Sclerostin Ab will begin in the next few months, says Dr. Harper. Initial investigations will involve the postmenopausal osteoporosis (PMO) setting where bone decay has already set in. The drug will also be designed for fracture healing.
But let’s not forget Amgen’s lead pipeline candidate, denosumab, which has a PDUFA date in October. It has been filed for approval as a treatment and prevention of PMO as well as for the treatment and prevention of bone loss in patients undergoing hormone ablation therapy for either prostate or breast cancer. So far, communications with the FDA have been positive, according to Dr. Harper. He hopes for an approval by the end of this year.
Some red flags that may be raised by the FDA include the fact that the drug has a novel mechanism of action and that it could be the first biologic to get approved in the primary-care setting. Another point of concern is the degree of bone suppression; oversuppression has hindered the bisphosphonate class of drugs. Dr. Harper notes that denosumab’s effects are reversible, unlike those of bisphosphanates.
Denosumab is also being studied in Phase II as a treatment for bone metastasis resulting from breast, prostate, and other cancers. These trials include higher doses given every month compared to denosumab in PMO, which is every six months. It is also being evaluated for its ability to delay and prevent bone metastasis.
If denosumab does get sanctioned in PMO, Amgen has a good life-cycle management strategy for the drug. By the middle of next year, we will begin to see whether Amgen’s innovation will lead to sustained growth.