FDA rejects first-in-class osteoporosis drug

Asher Mullard

The FDA rejected Amgen’s and UCB’s romosozumab, an anti-sclerostin monoclonal antibody that the firms are developing for the treatment of osteoporosis. The rejection followed on the heels of a cardiovascular safety signal that the companies reported in May. Amgen and UCB are now working to resubmit the application and hope to incorporate new data from ongoing phase III trials to address regulatory questions and concerns. Nearly all of the osteoporosis drugs that have been approved to date act by lowering bone resorption processes, but in doing so they also reduce bone-rebuilding activity. The one exception is Eli Lilly’s teriparatide, which boosts bone formation but also increases bone resorption. Researchers hoped that romosozumab might become the first drug that would decouple bone formation from bone resorption; the drug increases bone formation while simultaneously lowering bone resorption markers (Nat. Rev. Drug Discov. 15, 445–446; 2016).

The anti-sclerostin programme started in the 1990s and was spurred on by human genetic data that showed that loss-of-function mutations in the gene that encodes sclerostin leads to high bone mineral density without other adverse events (Nat. Rev. Drug Discov. 16, 515–518; 2017).

Clinical data supported the growing enthusiasm, with treatment leading to a 73% reduction in the relative risk of spine fracture at 12 months in a first pivotal phase III trial in postmenopausal women with osteoporosis. In May, however, the company reported that a second phase III trial found a 30% increase in cardiovascular events with romosozumab treatment. The companies are still working to understand the safety signal. At least one other anti-sclerostin drug is in clinical trials: in May, Mereo BioPharma initiated a phase II trial of the BPS-804 antibody in patients with osteogenesis imperfecta, a
genetic condition that is also known as brittle bone disease.

Fonte: Nature Reviews Drug Discovery | Published online 1 Sep 2017