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FDA Approves Treatment for Rare Genetic Enzyme Disorder
The FDA has approved the first treatment for children and adults with mucopolysaccharidosis type VII (MPS VII), an extremely rare, progressive condition that affects most tissues and organs.
Vestronidase alfa-vjbk (Mepsevii, Ultragenyx Pharmaceutical, Inc.) treats an inherited metabolic condition also known as Sly syndrome that impacts fewer than 150 patients worldwide. “Prior to today’s approval, patients with this rare, inherited condition had no approved treatment options,” said Julie Beitz, MD, director of the Office of Drug Evaluation III in the FDA’s Center for Drug Evaluation and Research.
The features of MPS VII vary widely from patient to patient, but most patients have various skeletal abnormalities that become more pronounced with age, including short stature. Affected individuals can also develop heart valve abnormalities, enlarged liver and spleen, and narrowed airways that can lead to lung infections and trouble breathing.
The life expectancy of individuals with MPS VII depends on the severity of symptoms. Some affected individuals do not survive infancy, while others may live into adolescence or adulthood. Heart disease and airway obstruction are major causes of death in people with MPS VII. Affected individuals may have developmental delay and progressive intellectual disability.
MPS VII is a lysosomal storage disorder caused by deficiency of an enzyme called beta-glucuronidase, which causes an abnormal buildup of toxic materials in the body’s cells. Vestronidase alfa-vjbk is an enzyme replacement therapy that works by replacing the missing enzyme.
The safety and efficacy of vestronidase alfa-vjbk were established in clinical trial and expanded access protocols enrolling a total of 23 patients ranging from 5 months to 25 years of age. Patients received treatment with vestronidase alfa-vjbk at doses up to 4 mg/kg once every two weeks for up to 164 weeks. Efficacy was assessed primarily via the six-minute walk test in 10 patients who could perform the test. After 24 weeks of treatment, the mean difference in distance walked relative to placebo was 18 meters.
Additional follow-up for up to 120 weeks suggested continued improvement in three patients and stabilization in the others. Two patients in the vestronidase alfa-vjbk development program experienced marked improvement in pulmonary function. Overall, the results observed would not have been anticipated in the absence of treatment. The effect of vestronidase alfa-vjbk on the central nervous system manifestations of MPS VII has not been determined.
The most common side effects after treatment with vestronidase alfa-vjbk include infusion site reactions, diarrhea, rash, and anaphylaxis.
The FDA granted this application fast track and orphan drug designations. The sponsor is receiving a rare pediatric disease priority review voucher.
The FDA is requiring the manufacturer to conduct a post-marketing study to evaluate the long-term safety of the product.
Source: FDA; November 15, 2017.