CAMBRIDGE, Mass.—Toward the end of 2017, Shire plc announced top-line results from its Phase 2/3 clinical trial evaluating SHP609 (previously known as HGT-2310), which is an investigational formulation of idursulfase administered intrathecally for a new potential indication for the treatment of pediatric patients with Hunter syndrome (mucopolysaccharidosis II, or MPS II) and cognitive impairment.
The study did not meet either its primary or its key secondary endpoint. The primary endpoint evaluated the difference in cognition between the SHP609-treated and control groups, as measured by change from baseline in General Conceptual Ability scores in children with Hunter syndrome after 12 months of treatment. The key secondary endpoint evaluated the difference between the SHP609-treated and control groups as measured by the change from baseline in Adaptive Behavior Composite score.
“Shire is disappointed that the top-line data from this study did not meet the primary and key secondary endpoints and remains committed to patients and families living with MPS II,” said Dr. Howard Mayer, a senior vice president at Shire. “We are grateful to the children, their families and healthcare providers for participating in this challenging trial and will continue our ongoing dialogue with the community as we conduct an analysis of the full data set. Further analysis of the data will be presented at forthcoming congresses.”
Hunter syndrome is a severely debilitating, rare lysosomal storage disorder (LSD) that affects one in 162,000 total live births, and is almost exclusively a male disease. This particular LSD is caused by a deficiency of iduronate-2-sulfatase, an enzyme that is needed to break down substances in the body called glycosaminoglycans (GAGs). Without this enzyme, GAGs can build up in and damage various organs, causing a range of disease-related signs and symptoms such as hearing loss, declined cardiac function, obstructive airway disease, enlargement of the liver and spleen and decreased range of motion and mobility. Physical manifestations may include distinct facial features, a large head and enlarged abdomen. In many cases the central nervous system may also be affected.
“Hunter syndrome is a severely debilitating rare genetic disorder ... Two out of three patients exhibit progressive cognitive decline, which is a high unmet need. This can be devastating for patients and their families, as it severely diminishes a child's functional ability and typically leads to death in the teenage years,” noted Dr. Joseph Muenzer, professor of pediatric genetics and metabolism genetics at the University of North Carolina Chapel Hill School of Medicine.
The company emphasized that Elaprase (idursulfase) for intravenous use continues to be an important medication for patients with Hunter syndrome in its current indication, which is for the treatment of Hunter syndrome in adults and children ages 5 and older, with the goal of improving walking capacity in these patients.