Synageva BioPharma Corp. (Synageva), a clinical stage biopharmaceutical company developing therapeutic products for rare diseases, today announced presentations at the upcoming LDN WORLD Symposium being held February 13-15 in Orlando, Florida. During an oral presentation on Friday, February 15, at 1:00 PM EST, Dr. Manisha Balwani will present 38-week data from the Phase I/II extension study of sebelipase alfa in adults with late onset lysosomal acid lipase deficiency (LAL Deficiency). An additional poster at the LDN WORLD Symposium will highlight the ability of SBC-103 to reduce the accumulation of substrate in the brain of a Mucopolysaccharidosis IIIB (also known as MPS IIIB, or Sanfilippo B) animal model.
Data Presentations and Synageva Satellite Symposium at the LDN WORLD Symposium
On Friday, February 15, at 1:00 PM EST, Manisha Balwani, MD, MS, Assistant Professor of Genetics and Genomic Sciences and Assistant Professor of Medicine, Mount Sinai School of Medicine, New York, NY, will present 38-week data from the Phase I/II extension study of sebelipase alfa. Nine adults with LAL Deficiency were enrolled in the Phase I/II trial. After completing the initial portion of the Phase I/II trial, patients were allowed to continue treatment with sebelipase alfa as part of a long-term, open-label extension study. Eight of nine patients have enrolled in the extension study and seven of these eight have now completed the first 38 weeks of the study.
Sebelipase alfa effects observed in this study at 24 weeks were sustained through 38 weeks. Sebelipase alfa continues to reduce liver damage with sustained reductions in both ALT and AST, frequently into the normal range. In addition, maintenance of the improvements in the dyslipidemia associated with LAL Deficiency was also observed. Sebelipase alfa produced mean percent decreases for ALT and AST from the initial baseline to week 38 of the extension study of 54% and 40%, respectively (p=0.016 for both comparisons). In addition, sebelipase alfa resulted in mean percent decreases from the initial baseline to week 38 of the extension study for LDL-C of 47% (p=0.016), total cholesterol of 33% (p=0.016), triglycerides of 29% (p=0.047), as well as a mean increase in HDL of 15% (p=0.313).
Sebelipase alfa was generally well tolerated throughout the initial 38 weeks of the extension study. The majority of adverse events were mild and unrelated to sebelipase alfa. Infusion-related reactions were uncommon and the majority were gastrointestinal (diarrhea, abdominal cramping) events of mild severity. One patient with a moderate (Grade 2) allergic type infusion-related reaction has paused treatment with sebelipase alfa pending further testing. No anti-drug antibodies have been detected in any subjects in either the initial portion or extension portion of the Phase I/II study. A single patient during the extension study developed acute cholecystitis and cholelithiasis (two serious adverse events) which were later treated with elective cholecystectomy. This patient has continued treatment with sebelipase alfa without changes in dosing and administration. These two serious adverse events were considered unlikely related to sebelipase alfa.
SBC-103 reduces accumulated substrate levels in the brain of a MPS IIIB mouse model
A poster entitled "Biochemical Evidence of the Effects of SBC-103, A Recombinant Human Alpha-N-Acetylglucosaminidase in a Mucopolysaccharidosis IIIB Mouse Model Using an Improved Analytical Method for Substrate Quantification," describes the preclinical activity of SBC-103.
Measurement of abnormal substrate in the brain has historically been challenging in this disease. This poster describes an improved method for quantifying heparan sulfate disaccharides (or HSD, the elevated substrate in MPS IIIB patients). This improved method showed clear increases in substrate in the MPS IIIB mouse disease model and that treatment with SBC-103 using various dosing approaches produced dose-dependent HSD level reductions in the brain, liver and kidney tissues of the mouse disease model.
An additional poster at this year's LDN WORLD Symposium is:
"Co-Localization of Macrophage Aggregation and Fibrosis in a Rat Model of Lysosomal Acid Lipase (LAL) Deficiency and the Effects of Enzyme Replacement with SBC-102," J. Rutkowski, et al.
Synageva-sponsored satellite symposium
On Friday, February 15th at 6:30-7:30 AM EST, Synageva will sponsor a breakfast symposium entitled, "LAL Deficiency: Are We Missing the Diagnosis and Does it Matter?" chaired by Gregory A. Grabowski, MD, The A. Graeme Mitchell Chair of Human Genetics, Professor and Director, Cincinnati Children's Hospital Medical Center.
About Synageva's Lead Program
Sebelipase alfa (formerly referred to as SBC-102) is a recombinant form of the human LAL enzyme under development by Synageva as an enzyme replacement therapy for LAL Deficiency, a lysosomal storage disorder (LSD). Synageva is currently evaluating sebelipase alfa in global clinical trials for both early and late onset LAL Deficiency. Sebelipase alfa has been granted orphan designations by the U.S. Food and Drug Administration (FDA), the European Medicines Agency, and the Japanese Ministry of Health, Labour and Welfare. Additionally, sebelipase alfa received "fast track" designation by the FDA.
About LAL Deficiency
LAL Deficiency is a rare autosomal recessive lysosomal storage disease caused by a marked decrease in LAL enzyme activity. Late onset LAL Deficiency, sometimes called Cholesteryl Ester Storage Disease (CESD), affects both children and adults. In these patients, the buildup of fatty material in the liver and blood vessel walls may lead to liver cirrhosis, liver failure and accelerated atherosclerotic events. Early onset LAL Deficiency, sometimes called Wolman disease, affects infants and is characterized by severe malabsorption, growth failure and liver failure, and is usually fatal within the first six months of life. There are no approved pharmacological therapies for LAL Deficiency. Success with stem cell and liver transplant appears to be limited by procedure-related morbidity and mortality.
About the LDN WORLD Symposium
The LDN WORLD Symposium is an ACCME-accredited annual symposium which includes lectures and poster presentations on basic, translational and clinical research for lysosomal storage disorders. The goal of the meeting is to provide an interdisciplinary forum to explore and discuss specific areas of interest, research and clinical applicability related to lysosomal diseases.
About Synageva BioPharma Corp.
Synageva is a clinical stage biopharmaceutical company focused on discovery, development, and commercialization of therapeutic products for patients with life-threatening rare diseases and unmet medical need. Synageva has several protein therapeutics in its drug development pipeline. The company has assembled a team with a proven record of bringing therapies to patients with rare diseases.
Further information regarding Synageva BioPharma Corp. is available at www.synageva.com.ContactMatthew Osborne781firstname.lastname@example.org