The US Food and Drug Administration (FDA) has approved Cyrstiva (burosumab) to treat patients with tumor-induced osteomalacia.
TIO is a rare paraneoplastic condition commonly characterized by bone pain, muscle weakness and fractures. These tumors secrete excess fibroblast growth factor 23 (FGF23) which inhibits the sodium phosphate renal co-transporters and suppresses 1α hydroxylase activity, thereby decreasing renal reabsorption and increased urinary phosphate excretion. As a result, unexplainable hypophosphatemia with a variety of musculoskeletal abnormalities are the common symptoms. Unfortunately, the symptoms are relatively non-specific and phosphate levels are not routinely included in many comprehensive metabolic panels and/or hypophosphatemia is often overlooked and patients are misdiagnosed with a variety of skeletal, rheumatologic, or neuro-psychiatric conditions.
Once diagnosed, treatment options include surgery to remove the tumor(s) but in about half of the patients, surgery is not an option and burosumab, an anti-GFG23 antibody, is a safe and effective option.
In a news release, Theresa E. Kehoe, MD, of the FDA said “As the first FDA-approved therapy to treat this debilitating disease, today’s action is an important step in finding treatment options for patients living with TIO whose tumor cannot be found or removed.”
The approval was largely based on two Phase 2 studies, a 144-week study in 14 adult patients in the United States and an 88-week study in 13 adult patients conducted in Japan and South Korea. In both studies, burosumab was associated with increases in serum phosphorus and serum 1,25-dihydroxy vitamin D levels. Bone scan results also indicated that some bone healing had occurred in the patients receiving burosumab.
Most common adverse reactions were tooth abscess, muscle spasms, dizziness, constipation, injection site reaction, rash, and headache.