Long path for Prolia

June 2, 2010 – 4:49 pm by Michael Christel

Amgen’s anticipated bone-strengthening drug, also known as denosumab, has notched approvals in Europe and the United States in the last five days, the latter almost two months ahead of schedule.

A whirlwind week to say the least for Amgen, a company whose fate, fair or not, has been pegged largely on Prolia, a twice-yearly injection that executives say is the most potent agent ever introduced to block bone degradation.

While you can tie a nice bow on the events of the last week, the road that preceded was not nearly as swift for the potential blockbuster biologic. Amgen chairman and CEO Kevin Sharer called FDA’s approval of Prolia – indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture – “the culmination of a scientific journey that started more than 15 years ago.�

That was when Amgen discovered RANK Ligand, an essential pathway that regulates osteoclasts, which are cells that remove bone tissue. Amgen scientists introduced a part of a gene into a transgenic mouse which encoded a protein called osteoprotegerin. This protein neutralizes the effects of RANK Ligand, keeping the bone loss process in check. The discovery unraveled the RANK Ligand/RANK osteoprotegerin axis, resulting ultimately in the development of Prolia.

The drug has since amassed a sizable clinical dossier, including data from the pivotal three-year Phase III study involving 7,808 patients that showed reduced vertebrae and hip fractures in postmenopausal women with osteoporosis.

Prolia hit a bump in the road last fall when FDA issued a complete response letter regarding Amgen’s biologics license application for osteoporosis, originally filed in December 2008. While not requiring further pre-marketing clinical trials for the treatment indication, the agency did request additional information. Amgen complied, and in February, FDA, after evaluating the resubmission, set an action date of July 25.

Back in our February 2008 issue, we profiled David Lacey, M.D., who was one of the Amgen scientists involved in the early development of Prolia. Dr. Lacey joined the company in 1994 as associate medical director in the department of experimental pathology. It was his and his colleagues discoveries in bone biology, including Rank Ligand, that helped spawn Prolia.

In the 2008 profile, Dr. Lacey merely expressed hope that his team’s discoveries would result in a biologically relevant medicine to treat the debilitating symptoms of osteoporosis and other bone disorders.

“The thrill of participating in research that may have the potential to help many people is what makes it exciting to come to work every day,� Dr. Lacey said at the time.

Now that potential has become reality. Amgen said Prolia will be available within the next two weeks and cost $825 per 60 milligram injection based on wholesale acquisition cost. Prolia commercialization is subject to an FDA-mandated risk evaluation and mitigation strategy program, consisting of a communication plan for healthcare providers and a medication guide for patients.

The company will also conduct comprehensive post-marketing surveillance, including following more than 4,500 women who started taking Prolia in clinical trials for up to 10 years.

While Prolia is the first new class of medicine introduced in nearly a decade to treat postmenopausal osteoporosis, analysts believe the drug with gradually penetrate the commercial setting at first, due in part to osteoporosis not having the same level of urgency associated with other debilitating conditions. Sales could approach $1 billion next year, rising to $2.9 billion annually by 2013, analysts estimate.

According to a recent report by EvaluatePharma, Prolia will become the industry’s tenth highest-selling product in 2016 at $5.2 billion in annual sales, factoring in the drug’s potential use in patients with cancer-related bone diseases, where Prolia has undergone several late-stage trials.

Last month, Amgen submitted a biologics license application asking FDA to approve Prolia to prevent or treat damage caused by bone metastases. The spread of tumors to the skeleton is an especially serious concern for many patients with advanced cancer. The application is supported by clinical experience from nearly 6,900 patients across 18 clinical studies, including about 5,700 patients with advanced cancer.

Prolia, among other Amgen drugs, will also be featured at this year’s ASCO meeting, which kicks off Friday, in a study evaluating the drug’s effectiveness in reducing fractures in prostate cancer patients.

Amgen has enrolled more than 11,000 patients in its oncology clinical trials for Prolia. The drug has been tested for the reduction of skeletal-related events in patients with breast and prostate cancer, as well as other solid tumors and multiple myeloma, for the amelioration of treatment-induced bone loss in patients with non-metastatic breast or prostate cancers, and for its potential to delay bone metastases in prostate cancer.

“What’s really important for patients is that we’ve learned over the last couple of years that there is a role for RANK Ligand and osteoclastic activity in osteoblastic disease,� Bill Dougall, Ph.D., Amgen’s scientific director of oncology research, said earlier this year. “The hope has been that there’s one key factor that drives cancer-induced bone disease, and that it’s applicable in many different tumor types and many different kinds of bone lesions that result from metastasis.�

Tags: Amgen, bone loss, cancer, denosumab, FDA, osteoporosis, Prolia