CAMBRIDGE, MA, USA I December 19, 2017 I Shire plc (LSE: SHP, NASDAQ: SHPG), the global leader in rare diseases, today announced top-line results from its Phase II/III clinical trial evaluating SHP609, previously known as HGT-2310. SHP609 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 (GCA) 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 (ABC) 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 Howard Mayer, M.D., Senior Vice President and Global Head of R&D (ad-interim), 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 genetic disorder caused by an enzyme deficiency which typically presents in early childhood,” said Joseph Muenzer, M.D., Ph.D., Professor of Pediatric Genetics and Metabolism Genetics, 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.”

ELAPRASE® (idursulfase) for intravenous use continues to be an important medication for patients with Hunter syndrome in its current indication. It remains approved in 70+ countries worldwide and is unaffected by these results.1,2,3

About Hunter Syndrome
Hunter syndrome affects 1 in 162,000 total live births, and almost exclusively males.4 It is a severely debilitating, rare lysosomal storage disorder (LSD) caused by a deficiency of iduronate-2-sulfatase, an enzyme that is needed to break down substances in the body called glycosaminoglycans (GAGs).5 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.5,6

Roughly two of every three patients with Hunter syndrome are also affected with progressive cognitive decline.7 SHP609 has been specifically developed to be directly administered via an injection into the cerebrospinal fluid as a means of delivering the drug to the central nervous system (intrathecal).7

About the Trial
SHP609 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. SHP609 is being investigated and developed for use with Shire’s current treatment for Hunter syndrome, ELAPRASE (idursulfase) which is administered intravenously and does not cross the blood-brain barrier in clinically relevant amounts.7

The Phase II/III study is a controlled, randomized, open-label, multi-center, assessor-blinded study designed to evaluate the effect of monthly intrathecal administration of SHP609 for 12 months on clinical parameters of neurodevelopmental status in pediatric patients with Hunter syndrome and cognitive impairment.8 The trial had an enrollment of 48 patients with Hunter syndrome and cognitive impairment who continued to receive and tolerate therapy with intravenous idursulfase.8

In the Phase II/III study, cognition was assessed by the Differential Ability Scale, Second Edition (DAS-II). One of the key secondary endpoints measured adaptive ability based on the Vineland Adaptive Behavioral Scales, Second Edition (VABS-II).8 VABS-II assesses the development of personal and social skills, including talking, walking and motor skills, as well as interpersonal relationships and coping skills.9

The safety profile observed was generally consistent with that seen in previous studies.7,10 Idursulfase-IT has been well studied with up to 67 months of patient exposure data. Of 15 patients in the Phase I/II trial of SHP609, all had ≥1 Treatment-Emergent Adverse Events (TEAE) and all had ≥1 drug-related TEAE. Of 54 serious TEAE types, 2 were believed to be causally related to idursulfase-IT: pyrexia (71 events, 3.3%) and vomiting (63 events, 2.9%).10

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About SHP609
SHP609 is an investigational formulation of idursulfase administered intrathecally for a new potential indication treatment of pediatric patients with Hunter syndrome (Mucopolysaccharidosis II or MPS II) and cognitive impairment.7

In clinical trials, SHP609 is administered to patients using an intrathecal drug delivery device.7 SHP609 is administered directly into the cerebrospinal fluid as a means of delivering the drug to the central nervous system.7

SHP609 has not been approved for use by the U.S. Food and Drug Administration, European Medicines Agency or other regulatory authorities.

About ELAPRASE (idursulfase)
ELAPRASE is an intravenous enzyme replacement therapy approved for the treatment of patients with Hunter syndrome in 70+ countries worldwide including countries in Africa, Asia Pacific, Europe, Latin America and North America.1

In the E.U., ELAPRASE▼ is indicated for the long-term treatment of patients with Hunter syndrome.2

This medicinal product is subject to additional monitoring in the E.U. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed here.

U.S. Indication and Usage

ELAPRASE (idursulfase) is indicated for patients with Hunter syndrome (mucopolysaccharidosis II or MPS II). ELAPRASE has been shown to improve walking capacity in patients 5 years and older.3

In patients 16 months to 5 years of age, no data are available to demonstrate improvement in disease-related symptoms or long-term clinical outcome; however, treatment with ELAPRASE has reduced spleen volume similarly to that of adults and children 5 years of age and older.

The safety and efficacy of ELAPRASE have not been established in pediatric patients less than 16 months of age.

About Shire

Shire is the global leader in serving patients with rare diseases. We strive to develop best-in-class therapies across a core of rare disease areas including hematology, immunology, genetic diseases, neuroscience, and internal medicine with growing therapeutic areas in ophthalmics and oncology. Our diversified capabilities enable us to reach patients in more than 100 countries who are struggling to live their lives to the fullest.

We feel a strong sense of urgency to address unmet medical needs and work tirelessly to improve people’s lives with medicines that have a meaningful impact on patients and all who support them on their journey.

1 Elaprase. R&D DoF ID: DOF-RDX006A-007. Shire. SME-Medical Communications. August 2017.
2 ELAPRASE Summary of Product Characteristics. European Medicines Agency. Last updated October 2016. Available at:
3 ELAPRASE U.S. PRESCRIBING INFORMATION. United States Food and Drug Administration. Last updated June 2013. Available at
4 Meikle PJ et al. Prevalence of Lysosomal Storage Disorders. JAMA. 1999. 281(3):249-54.
5 Wraith JE et al. Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy. Eur J Pediatr. 2008. 167(3):267-77.
6 Wraith JE. Idursulfase for enzyme-replacement therapy in mucopolysaccharidosis II. Therapy. 2007. 4(3):231-240.
7 Muenzer J et al. A phase I/II study of intrathecal idursulfase IT in children with severe mucopolysaccharidosis II. Genet Med. 2016. 18(1):73-81.
8 Study of Intrathecal Idursulfase-IT Administered in Conjunction With Elaprase in Pediatric Patients With Hunter Syndrome and Early Cognitive Impairment. Available at: Accessed December 2017.
9 Sparrow S. Vineland Adaptive Behavior Scales. (Technical Manual)second ed. Pearson, Bloomington, MN; Accessed December 2017.
10 Muenzer J et al. A Long-term Extension Study Evaluating Intrathecal Idursulfase-IT in Children with Hunter Syndrome and Cognitive Impairment. Presented at the 13th Annual WORLDSymposium, February 13-17, 2017, San Diego, CA.