The US Food and Drug Administration (FDA) on Monday issued new draft guidance calling for drugmakers to conduct long-term nonclinical bone quality studies for osteoporosis treatments.
According to FDA, such studies are necessary for osteoporosis drugs to determine whether the drugs result in poorer bone quality when taken for long periods of time. Additionally, FDA says these studies should be nonclinical, as "there are no validated and reliable methods for the noninvasive assessment of bone quality in humans."
"Although bone quality cannot be easily assessed directly, nonclinical studies offer the opportunity to develop indirect information about bone quality through the measurement of bone strength, which is determined by both bone mass and bone quality," FDA writes.
For most drugs, FDA says companies should conduct studies in two animal species. FDA makes specific species recommendations for postmenopausal osteoporosis, the most common form of the disease. For drugs targeting postmenopausal osteoporosis, FDA says bone quality studies should be conducted in ovariectomized rats, with a more extensive study in a second large mammal species such as nonhuman primates, sheep, pigs or dogs.
However, FDA says that biologics may not be required to conduct these tests in animals, as species selection for biologics can be difficult as the receptor or antigen target of the compound may not be present in common study animals, or if present, may not interact with the treatment molecule. In these cases, FDA says sponsors should choose an animal model based on pharmacological responsiveness.
As such, FDA says that biological sponsors may only need to conduct an animal study in one species. In cases where a relevant animal model cannot be found, FDA says biologics sponsors should look to alternatives, such as the use of a surrogate drug or by genetically modifying an animal species to "express the human target."
FDA also says that companies developing anabolic drugs to treat osteoporosis study the carcinogenetic potential of the drugs. According to the agency, previous studies have shown potential for bone tumor growth in mice and rats when given parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP) drugs.
Additionally, FDA calls on drugmakers to seek early input from its Division of Bone, Reproductive, and Urologic Products on nonclinical bone quality studies, adding that "study protocols with detailed descriptions of testing procedures should be submitted for review by the division."