Shire’s Hunter Syndrome Trial Fails to Meet Primary Endpoint While Advocacy Group Starts its Own Gene Therapy Trial.

Pharmaceutical giant, Shire, announced that its phase 2/3 clinical trial involving children with Hunter syndrome receiving intrathecal infusions of idursulfase failed to meet its primary and secondary endpoints. There is currently an approved idursulfase (Elaprase) that is given intravenously but that enzyme replacement therapy cannot cross the blood brain barrier, and as a result, two-thirds of those patients will show cognitive decline due to the accumulation of glycosaminoglycans (GAGs) in neural tissue that cannot be broken down by idursulfase. It was hoped that intrathecal administration of idursulfase would attenuate the cognitive decline but the phase 2/3 study did not observe that.

In the study, 48 patients with Hunter syndrome who had cognitive impairment were given intravenous and intrathecal idursulfase. While details of the results have not been made available, the company did report that the study did not meet its primary and secondary endpoints. The primary endpoint was the difference in cognition between the SHP609 (intrathecal idursulfase)-treated and control groups, as measured by change from baseline in General Conceptual Ability (GCA) scores in children with Hunter syndrome after 12 months of treatment.

Hunter syndrome is a rare lysosomal disorder due to a deficiency of iduronate-2-sulfatase, an enzyme needed to break down glycosaminoglycans (GAGs). Without this enzyme, GAGs can build up in and damage various organs, leading to a range 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. In addition, approximately two-thirds of Hunter syndrome patients show progressive cognitive decline.

One door closes, another one opens

The knowledge that current therapy for Hunter syndrome is not adequate to stop the cognitive decline in patients with Hunter syndrome was one of the impetuses for many Hunter syndrome families to do their own fundraising to invest in a gene therapy for his rare condition. Those parents, as part of Project Alive just announced they have signed a $1.4 million agreement with Nationwide Children’s Hospital in Columbus, Ohio, to fund the production of gene vector for a Phase I/II clinical trial in patients with Hunter syndrome.

Project Alive has been raising money and awareness about Hunter syndrome for a couple years and is led by Melissa Hogan, a parent of a child with the rare disease. Among the methods used to raise money were a documentary series about Hunter Syndrome that led Melissa and her family to be included in the American television show, “The Doctors.”