RPT-PREVIEW-US review of Amgen bone drug to focus on safety

Mon Aug 10, 2009 8:09am EDT

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* Infection risk at forefront

* Panel expected to recommend approval

By Deena Beasley

LOS ANGELES, Aug 9 (Reuters) - Thursday's U.S. Food and Drug Administration advisory panel review of denosumab, Amgen Inc's (AMGN.O) experimental osteoporosis drug, will likely center on safety, particularly the risk of serious infections.

Denosumab -- to be sold under the brand name Prolia -- is seen as Amgen's best hope of jump-starting growth now that safety concerns have deflated sales of its flagship anemia drugs.

The biotech company filed in December for approval of denosumab as a treatment for post-menopausal osteoporosis and for treating and preventing bone loss in patients undergoing hormone ablation for either prostate or breast cancer.

Given denosumab's easy administration and infrequent dosing, "a lot (of osteoporosis patients) will end up being treated with this drug right off the bat," said Dr.John Adams, an endocrinologist at the University of California, Los Angeles who was not involved in denosumab's development.

"We do think that ultimately it (denosumab) is going to get approved," said Cowen & Co analyst Craig Gordon. "I think what's unclear is the extent of post-marketing commitments Amgen will be required to do."

BRIEFING DOCUMENTS ON TUESDAY

Investors will get a sense of the FDA's thinking on Tuesday, when the agency is expected to release internal memos with a preliminary analysis of Amgen's denosumab data.

FDA reviewers will present the views to the advisory panel on Thursday before the outside experts make recommendations on the drug. The agency usually follows committee advice when making final approval decisions.

Denosumab is also being developed for treating bone loss in cancer patients.

BMO Capital Markets analyst Jason Zhang estimated combined sales of denosumab in the osteoporosis and oncology markets of $2.4 billion by 2012.

Trials of the drug in post-menopausal women with osteoporosis found that it reduced the risk of spine fractures by nearly 70 percent, but some studies showed a higher rate of serious skin infections that required hospitalization.

Amgen is banking on the impressive clinical data, along with a patient-friendly dosing schedule of twice-yearly injections to help it compete with existing osteoporosis drugs, some of which are already available as low-cost generics.

RISK MANAGEMENT PLAN?

Denosumab is a bioengineered antibody that targets RANK ligand, a protein involved with bone-destroying cells called osteoclasts.

In addition to infection risk, the FDA committee is also likely to discuss the risk of cataracts, since an imbalance of incidence was seen in one trial, and the risk of a rebound in bone turnover markers, said Gordon at Cowen & Co.

"We expect the FDA to basically concede efficacy and mostly just address safety," he said.

The FDA may approve the drug with a required risk management plan to minimize side effects, an increasingly common scenario for new medicines. The agency can mandate post-approval studies, distribution limits or other measures.

Bad news for the stock would include a recommendation for a stringent risk management plan, which could limit the likelihood that a doctor would prescribe the drug.

In the best case, the panel would simply call for active surveillance of side effects, Gordon said.

Dr. Adams said the risk of infection with denosumab could be mitigated by ensuring that patients are getting sufficient vitamin D before they are started on the drug.

"RANK ligand is made by the body's lymphocytes -- part of the immune system," he said. "When you give this drug (denosumab) to someone who is vitamin D deficient, they are doubly immuno-compromised."

In the cancer setting, where a much higher dose of the drug is used, questions have been raised about the risk of osteonecrosis -- or deterioration -- of the jaw, a serious side effect associated with some other osteoporosis drugs.

The FDA is slated to issue a decision on the denosumab marketing application by Oct. 19, but many on Wall Street expect that the deadline could be missed given the agency's recent track record of delayed decisions. (Additional reporting by Lisa Richwine in Washington; Editing Bernard Orr)

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