The Dawn of the Era of Genomic Medicine

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On June 1, the FDA approved a new treatment for osteoporosis. The discovery of the drug, denosumab (trade name Prolia) was based on an early application of genomic technology. Denosumab is approved for treatment of women, post menopause, with osteoporosis who have a high risk for fractures. The drug, given as an injection every six months, substantially reduces the risk of fractures of the hip, spine and neck.

The new drug is a product of genomic discoveries. Fifteen years ago, scientists at Immunex, a company later acquired by Amgen, discovered a new gene that specifies a protein, osteoprotregerin, which stimulates the cells, called osteoclasts, that are responsible for bone degradation. They made the discovery employing what were then the new rapid genomic based gene identification techniques. Scientists developed an antibody that works to block the action of osteoprotegerin. The antibody (the drug denosumab) binds to a protein called RANK Ligand, preventing osteoclasts from destroying bone. RANK Ligand is necessary for the formation, survival and function of the osteoclasts that destroy bone. 

Over the years, I have followed this work very closely as at about the same time researchers at Human Genome Sciences, the company I founded, made the same discovery using similar genomic methods. We began a program to develop the drug but abandoned it when we realized that Immunex and then Amgen were far in the lead.

The trials that lead to approval of denosumab were extensive. Over 7,800 women who had finished menopause were treated for three years. The women who received the drug were reported to experience almost 70 percent fewer fractures of the vertebrae and a 40 percent reduction in hip fractures. Women on treatment showed significant increases in bone density of the spine, hip and neck.

Denosumab offers a new way to treat osteoporosis. One class of drugs called bis-phosphonates has been approved for many years. The side effects of these drugs, primarily acid reflux, often limit their use. Although it is recommended that people take bis-phosphonates continually, most give it up after a single year. Another drug, an injectable form of parathyroid hormone, called Forteo, actually builds new bone. Last time I checked, this drug was approved for use for two years only. Blocking the action of bone destroying cells with denosumab offers new hope for many women.

Like any drug, denosumab is not free of side effects. The risk of skin rashes and some infections including cellulitis and endocarditis may be increased. Denosumab, like the bis-phosphonates, may also slow the repair of broken bones and impair a natural process called bone remodeling, whereby our bodies reshape our bones according to stress. Nonetheless, on balance, in the group treated, the benefits far outweighed the risks. Amgen is now conducting additional long term studies to assess the long term safety of the drug. Four thousand women taking the drug will be followed for ten years. Now, after almost twenty years of research, new genomic based medicines are beginning to reach people in need. I have previously written here about two other genomics based drugs, one for the treatment of lupus and the other for prevention of heart attacks, stroke and other vascular diseases. I believe that we are, at long last, at the dawn on the era of genomic medicine.

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William Haseltine is a former professor at Harvard Medical School, where he researched cancer and HIV/AIDS. He is the founder of Human Genome Sciences, where he served as chairman and CEO, and the president of the William A Haseltine Foundation for Medical Sciences and the Arts. He lives in Washington, D.C.

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