Rare Daily Staff

Rare disease drugmaker Shire said that its experimental therapy SHP609 for MPS II, also known as Hunter Syndrome, failed to meet its primary and key secondary endpoint in a phase 2/3 study.

MPS II is a severely debilitating, rare lysosomal storage disorder caused by a deficiency of iduronate-2-sulfatase, an enzyme that is needed to break down substances certain carbohydrates in the body. 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.

Roughly two of every three patients with Hunter syndrome are also affected with progressive cognitive decline. Shire developed SHP609 to be directly administered via an injection into the cerebrospinal fluid as a means of delivering the drug to the central nervous system.

Top-line results from its phase 2/3 trial found SHP609 failed to produce a difference in the study’s primary endpoint of 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.

“Hunter syndrome is a severely debilitating rare genetic disorder caused by an enzyme deficiency which typically presents in early childhood,” said Joseph Muenzer, professor of Pediatric Genetics and Metabolism Genetics at the University of North Carolina Chapel Hill School of Medicine. “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.”

December 19, 2017