-Data Presented as Late-Breaker at WORLDSymposium™ 2016-
MPS IIIB is caused by genetic mutations that result in a marked decrease in N-acetyl-α-D-glucosaminidase (NAGLU) enzyme activity, leading to abnormal accumulation of HS in the brain and other organs. This results in severe neurocognitive decline, behavioral disturbances, speech loss, increasing loss of mobility, and premature death.2
"MPS IIIB is a severe and progressive disorder characterized by systemic and central nervous system (CNS) morbidities, with devastating and life-threatening outcomes for affected children. SBC-103 is manufactured with our proprietary protein expression platform, and we are encouraged by its potential to be administered intravenously and cross the blood-brain barrier to provide both systemic and CNS clinical benefits for patients suffering from MPS IIIB," said Martin Mackay, Ph.D., Executive Vice President and Global Head of R&D at
Eleven children with MPS IIIB (ages 2 years to 10 years at study entry) were enrolled in the first-in-human study, which included three parallel dosing groups of intravenous SBC-103 (0.3, 1.0 and 3.0 mg/kg qow). The primary endpoint of the ongoing trial is safety and tolerability, and key secondary endpoints presented at WORLDSymposium include changes from baseline in HS levels in CSF and serum as well as pharmacokinetics (PK) and pharmacodynamics (PD). Additional secondary endpoints related to neurocognitive outcomes, brain structure, and changes in HS levels in urine are also being evaluated.
Most adverse events (AEs) in the study were mild and unrelated to SBC-103, and no patient discontinued the study. Of 11 patients in the study, two patients experienced a total of four serious AEs (bacteremia, pyrexia, staphylococcal bacteremia, and cyanosis [pre-treatment]) that were deemed not related to SBC-103. Six infusion-associated reactions occurred in three patients (pyrexia, chills, hypertension, and tachycardia).1
At 24 weeks of treatment, the analysis showed a 26.2 percent mean reduction from baseline in total HS CSF in the 3 mg/kg (N=4) dosing cohort. These data are directionally consistent with reductions in brain HS observed in the NAGLU -/- mouse model. Patients in the 0.3 mg/kg (N=3) and 1.0 mg/kg (N=4) groups had a 10.9 percent mean increase and a 0.4 percent mean decrease in HS CSF, respectively. Additionally, researchers reported mean reductions in total serum HS at 24 weeks of 39.6 percent, 53.9 percent, and 40.5 percent at 0.3, 1.0 and 3.0 mg/kg, respectively. These findings are directionally consistent with reductions in liver HS observed in the NAGLU -/- mouse model. Researchers also reported PK findings for SBC-103 at 24 weeks, noting that individual HS CSF reduction levels were linearly correlated with an increase in serum PK exposures.1
An interim 12-week analysis from the Phase 1/2 study reported in
About Mucopolysaccharidosis IIIB (MPS IIIB)
MPS IIIB (also known as Sanfilippo B syndrome) is a genetic, progressive, and devastating rare lysosomal storage disease. In patients with MPS IIIB, genetic mutations result in a marked decrease in N-acetyl-α-D-glucosaminidase (NAGLU) enzyme activity, which leads to the accumulation of heparan sulfate (HS) in the brain and other organs. The accumulation of abnormal HS leads to progressive brain atrophy, neurocognitive decline, behavioral disturbances, speech loss, increasing loss of mobility, and premature death.2 MPS IIIB typically presents in children during the first few years of life, and patients have a greater than 50 percent mortality rate by 17 years of age.3
There are no approved treatments for patients with MPS IIIB. Current supportive care is palliative for behavioral problems, sleep disturbances, seizures, and other complications, and does not address the root cause of MPS IIIB or stop disease progression.2,3
About SBC-103
SBC-103 (rhNAGLU enzyme) is an enzyme replacement therapy being investigated in a Phase 1/2 trial for patients with MPS IIIB. It is a recombinant form of the N-acetyl-α-D-glucosaminidase (NAGLU) enzyme intended to reduce accumulated heparan sulfate by replacing the missing or deficient NAGLU enzyme. SBC-103 was granted orphan designation by the
SBC-103 utilizes Alexion's proprietary protein expression platform, a novel production process that has the potential to enable enzyme replacement therapies (ERTs) to cross the blood-brain barrier.
About
[ALXN-G]
Forward-Looking Statements
This news release contains forward-looking statements, including statements related to potential medical benefits of SBC-103 for mucopolysaccharidosis IIIB (MPS IIIB). Forward-looking statements are subject to factors that may cause
References | ||
1. |
Whitley CB, Escolar ML, Vijay S, et al. Initial, 24 Week Results of Heparan Sulfate Levels in Cerebrospinal Fluid (CSF) and Serum in an Open Label, Phase I/II, First-in-Human Clinical Trial of Intravenous SBC-103 in Mucopolysaccharidosis IIIB. Poster presented at WORLDSymposium Annual Meeting 2016, |
|
2. | Wijburg FA, Wegrzyn G, Burton BK, Tylki-Szymanska A. "Mucopolysacchardosis type III (Sanfilippo syndrome) and misdiagnosis of idiopathic developmental delay, attention deficit/hyperactivity disorder or autism spectrum disorder." |
|
3. | Heron, B., et al. Am. J. Med. |
View source version on businesswire.com: http://www.businesswire.com/news/home/20160301006917/en/
Media
Senior Vice President, Corporate Communications
OR
Associate Director, Corporate Communications
OR
Investors
Vice President, Investor Relations
Source:
News Provided by Acquire Media