FDA Approves Burosumab-twza for Tumor-Induced Osteomalacia

The FDA has approved burosumab-twza (Crysvita) injection for the treatment of patients aged 2 and older with tumor-induced osteomalacia (TIO), which is described as the development of tumors that cause weakened and softened bones.

“Treatment for TIO focuses on identifying and removing the tumor that causes the disease. However, when that is not possible, [burosumab] can help increase the levels of phosphate in the blood,” Theresa E. Kehoe, MD, acting director of the Division of General Endocrinology of the FDA’s Center for Drug Evaluation and Research said in a press release. “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 tumors linked with TIO release a peptide hormone-like substance known as FGF23 that lowers phosphate levels. FGF23 controls levels of phosphate, which plays a pivotal role in bone maintenance, energy production by cells, as well as nerve functionality. When there is not enough phosphate present within the body, bones will start to soften and weaken, resulting in osteomalacia.

The regulatory decision was based on safety and efficacy data from 2 studies that collectively enrolled a total of 27 patients with TIO. In both of these studies, patients were given burosumab every 4 weeks. In the first study, half of the participants achieved normal phosphate levels through week 24 and retained normal or near normal phosphate levels through week 144. Notably, results from bone scans conducted in patients enrolled on this trial suggested healing of osetomalacia-related bone lesions. Data from the second study revealed that 69% of patients achieved normal phosphate levels through week 24 and retained normal or near normal phosphate levels through week 88.

With regard to safety, hypersensitivity reactions, including rash and hives, were observed in patients who received the agent. If serious reactions occur, the FDA recommends that patients stop treatment. Moreover, higher than normal levels of phosphorous could potentially be linked with an increased risk of nephtocalcinosis, according to the FDA.

The most common adverse events reported with the agent included tooth abscess, muscle spasms, dizziness, constipation, injection site reaction, rash, as well as headaches.

The following patients should not receive treatment with the agent: those receiving oral phosphate or active vitamin D, those with serum phosphate levels within or above the normal range for their age, and those with either severe kidney impairment or end-stage renal disease.

Previously, the agent was approved by the FDA for use in adults and children 6 months and older with X-linked hypophosphatemia, which leads to low levels of phosphate in the blood and results in impaired bone growth and development in children and teenagers.

Reference

FDA approves first therapy for rare disease that causes low phosphate blood levels, bone softening. News release. FDA. June 18, 2020. Accessed June 22, 2020. bit.ly/2YmUm0g.