SUMMARY
Currently approved therapies for osteoporosis can reduce spine fracture risk by 50-75% and hip
fracture risk by up to 50%. However, due to fears about very rare side effects, use of
osteoporosis medications has declined by 50% since 2008. Therefore, there is a strong need
for new therapies that have a strong safety profile, perhaps greater efficacy and convenient for
the patient. However, new trials require fracture endpoints and must be very large: as long as 5
years with > 16,000 patients making the development of new medications extremely expensive
and no longer feasible.
The FNIH-ASBMR-SABRE (Study to Advanced BMD as a Regulatory Endpoint) began in 2013
with a primary goal of qualifying the treatment-related change in bone mineral density (BMD) as
a surrogate endpoint in future trials of new anti-osteoporosis therapies. Successful completion
of this goal would prompt innovation and facilitate new drug development. To this end, we have
collected individual patient data from >150,000 patients in >50 randomized trials and used this
unique resource to perform analyses to determine a strong relationship between larger BMD
increase and greater fracture reductions in those trials.
Starting in 2016, we began work with the FDA to obtain formal qualification of change in DXA
BMD as a surrogate endpoint for fracture in future trials. To date, our Letter of Intent and
Qualification Plan have been approved by the FDA. The current proposal will fund our continued
work with FDA to complete the final steps outlined in the 2017 Biomarker Qualification
Guidelines, namely submission of the Full Qualification Package. To do so, we will need to
meet regularly with the FDA, respond to the suggestions in the review of the Qualification Plan,
finalize the FQP and the submission of data documentation according to FDA specifications.
The qualification of BMD change as a surrogate endpoint for fracture in future trials of anti-
osteoporosis therapies would be a breakthrough in the field that would lead to expedited
development of new medications and enormous benefits for osteoporosis patients and public
health.
