The Foundation for the National Institutes of Health (FNIH) announces that the Food and Drug Administration (FDA) has qualified the treatment-related change in hip bone mineral density (BMD) as a surrogate endpoint for bone fractures in clinical trials of anti-osteoporosis drugs in post-menopausal women at risk for osteoporotic fracture.

“This achievement will help reduce barriers to developing new treatments that ultimately will improve quality of life for many patients ... It represents a fundamental shift in the way clinical studies will be performed ..."— Tania Kamphaus, MSc, PhD

Clinical trials investigating new osteoporosis therapies have traditionally relied on bone fractures as the primary measure of effectiveness. Trials were designed to follow thousands of participants for a lengthy period to determine if a drug prevented fractures, making the trials prohibitively expensive. With this new qualification, a change in BMD can now serve as the primary endpoint in future trials, replacing fracture rates and significantly reducing the time and expense required to develop and deliver much-needed treatments. BMD is measured via dual-energy X-ray absorptiometry (DEXA), a routine, noninvasive and relatively inexpensive imaging test.

“This milestone achievement will help reduce barriers to developing new treatments that ultimately will improve quality of life for many patients and their families. It represents a fundamental shift in the way clinical studies will be performed in the future,” said Tania Kamphaus, MSc, PhD, Associate Vice President, Science Partnerships, and Director of Patient Engagement at the FNIH. “It also highlights the critical importance of public-private partnerships to accelerate medical breakthroughs.”

The Study to Advance BMD as a Regulatory Endpoint (SABRE), which generated the data and evidence for this qualification, is a public-private partnership launched and managed by the FNIH Biomarkers Consortium. Principal investigators Dennis Black, PhD, from the University of California, San Francisco, and Mary Bouxsein, PhD, from Beth Israel Deaconess Medical Center and Harvard Medical School, led the research. The study brought together the resources and expertise of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) at NIH, guided by Gayle Lester, PhD; the American Society for Bone and Mineral Research (ASBMR); academic researchers; and several life science companies, many of which donated their clinical trial data to the study.

The project team assembled and reviewed existing patient data—donated by more than 10 companies and NIH, which included more than 160,000 participants across 52 clinical trials of osteoporosis drugs—to identify measures that predict a drug’s ability to reduce incidence of fractures. Analyses showed a strong association between an increase in hip BMD following treatment and a subsequent reduction in fracture risk. The findings provided robust evidence that a change in BMD could reliably demonstrate the effectiveness of osteoporosis drugs used in clinical trials.

Through the support of ASBMR, the investigators were able to extend the original study to seek formal approval for the surrogate endpoint through the FDA Biomarker Qualification Program. This is the first surrogate endpoint to receive qualification through the program, which works with external stakeholders to develop and formally qualify measurable and reliable biomarkers for a specific use in drug development.

“Drugs for reducing fractures are available, but treatment rates have markedly declined due to concerns about very rare side effects, inconvenient dosing, and limited effectiveness against some types of fractures,” said Dr. Black. “This FDA decision will help address the treatment gap for osteoporosis by accelerating development of new therapies and providing more options to patients and clinicians.”

Osteoporosis is a chronic condition that develops when bone mass decreases with aging, a process that is accelerated by menopause in women. In the United States, more than 10 millionolder adults have osteoporosis, and another 43 million are at high risk. After the age of 50, one in three women and one in five men will suffer a bone fracture due to the disease. The clinical, medical, and societal burdens are significant and growing: Fractures caused by osteoporosis are expected to rise to 3.2 million annually by 2040, with related health care costs rising to $95 billion per year in the United States. Hip fractures, in particular, represent a huge health burden, often leading to long-term disability and premature death.