FDA Approves Biomarker Qualification Plan for the First Surrogate Endpoint in Anti-Osteoporosis Drug Trials
North Bethesda, MD, June 1, 2022—The Foundation for the National Institutes of Health (FNIH) announces that the Food and Drug Administration (FDA) Biomarkers Qualification Program accepted a qualification plan to use the treatment-related change in bone mineral density (BMD) as a surrogate endpoint for fractures in future trials of new anti-osteoporosis drugs. The qualification plan submission was an accomplishment of the Study to Advance BMD as a Regulatory Endpoint (SABRE), or Bone Quality Project, which is managed by the FNIH and supported financially through a partnership with the American Society for Bone and Mineral Research (ASBMR). This is the first qualification plan accepted by the FDA for a surrogate endpoint under the 21st Century Cures Act, a 2016 law that aims to bring medical advances and innovations to patients faster and more efficiently. The project team plans to submit a full qualification package per this approved plan for final approval by the FDA before the end of this year.
According to the National Center for Health Statistics, Centers for Disease Control and Prevention, more than 60 million people in the United States have or are at a high risk for osteoporosis, a bone disease that develops when bone mass decreases, leading to an increase in the risk of bone fractures. Fractures, particularly of the hip, are considered the most serious consequence of osteoporosis, which predominantly affects postmenopausal women and older men.
“Currently, clinical trials for new drugs for osteoporosis use fractures as their main outcomes, requiring many patients to be followed over several years and are therefore expensive, painful, and long. The use of a reliable and pain-free measurement that can serve as a surrogate endpoint and replace fracture can significantly reduce the cost and length of new clinical trials, hence improving our ability to bring new treatments to patients,” said Dennis Black, PhD, Principal Investigator on the project at the University of California, San Francisco.
Initiated in 2013, the FNIH Biomarkers Consortium Bone Quality Project assembled data from over 150,000 participants in over 50 clinical trials of osteoporosis drugs. The project team reviewed these data to identify measurements that could be used to predict the ability of a drug to successfully reduce fractures. The study findings identified a decrease in bone mineral density, as measured by a low-dose X-ray imaging technique, as a strong predictor of fracture. An increase in bone mineral density could therefore be used in future clinical trials to determine the effectiveness of osteoporosis drugs. The FNIH-ASBMR SABRE project extended the original study to seek FDA approval for the surrogate biomarker.
“The ultimate goal of using a surrogate endpoint is to decrease the need for actual fracture outcomes in future trials. Development and use of a surrogate endpoint will reduce the barrier for new drug development and thereby promote innovation, ultimately reducing the pain and suffering related to fragility fractures in older adults,” said Mary Bouxsein, PhD, Director, Center for Advanced Orthopedic Studies at Beth Israel Deaconess Medical Center, and Co-Principal Investigator on the project.
“The FDA Biomarkers Qualification Program is important for developing measurable and reliable biomarkers that can be used as drug development tools in clinical trials and ultimately have the potential for advancing public health,” said an FDA spokesperson.
“This project brought together researchers from the University of California San Francisco, Harvard Medical School, and the University of Sheffield in the United Kingdom, as well as leading experts from the National Institutes of Health (NIH), industry, and patient advocacy partners to assemble this remarkable database to make this study possible,” said Steve Hoffmann, Director of the FNIH Biomarkers Consortium.
“The ASBMR is proud to financially support this critical initiative. Achieving FDA approval to utilize BMD as a surrogate endpoint in future osteoporosis drug development trials could provide patients with more options to fight a disease that leads to debilitating fractures that cause disability, loss of independence, and even death. It is also likely to attract more researchers to the musculoskeletal field, enabling a new horizon of discoveries to help our patients,” said Peter R. Ebeling, AO, FRACP, MBBS, MD, President, ASBMR.
“This effort illustrates the benefits of data sharing and collaborative projects,” said Gayle Lester, PhD, Director of the Division of Extramural Research at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). “In addition to laying the groundwork for much needed patient therapies, the SABRE investigators have created a rich dataset that holds promise for informing future studies in osteoporosis.”
The FNIH created a public-private partnership to execute the Bone Quality Project and enabled SABRE to take the next steps toward qualification. This partnership has brought together expertise and resources from the FDA and NIH, academia, industry, and advocacy organizations:
National Institute on Aging
National Institute on Arthritis and Musculoskeletal and Skin Diseases
U.S. Food and Drug Administration
American Society for Bone Mineral Research
Daiichi Sankyo, Inc.
Eli Lilly and Company
Merck Sharp & Dohme LLC
National Dairy Council
Roche Diagnostics Corporation
Beth Israel Deaconess Medical Center
Harvard Medical School
University of California San Francisco
University of Pittsburgh
University of Sheffield, United Kingdom