Natural history of infants with LAL DeficiencyA poster at this year’s LDN WORLD Symposium described the natural history of infants with LAL Deficiency. Thirty-five infants who fulfilled the eligibility criteria with a clinical diagnosis of LAL Deficiency presenting in infants, historically called Wolman disease, were enrolled in the study. The median age (range) for patients at symptom onset, diagnosis, and death was 1.0 month (0 - 6.0), 2.6 months (1.0 - 17.7), and 3.7 months (1.4 - 46.3), respectively. Growth failure and aggressive liver disease contributed to early mortality. Transaminase levels (ALT and/or AST), abnormal at diagnosis, markedly increased with disease progression. Hematopoietic stem cell transplants were performed in 10 infants; seven of these 10 infants died before nine months of age and three infants died between 26.9-46.3 months of age. Sebelipase alfa continues to improve disease abnormalities at 90 weeks from an ongoing Phase 1/2 trial in adults with LAL Deficiency As part of an oral presentation, Chester B. Whitley, PhD, MD, Professor, Director of the Gene Therapy Center, Advanced Therapies and PKU Clinic, Department of Pediatrics and Experimental and Clinical Pharmacology at the University of Minnesota, Minneapolis, MN, provided an update from six adult patients treated with sebelipase alfa at 90 weeks. Patients continued to demonstrate sustained reductions in the biomarkers of liver damage (both ALT and AST), frequently into the normal range, from the pre-treatment baseline. In addition, sebelipase alfa maintained improvements in dyslipidemia associated with LAL Deficiency, with decreases in LDL and triglycerides and increases in HDL from the pre-treatment baseline to week 90 of the extension study. Sebelipase alfa was generally well tolerated through 90 weeks of the extension study. Most adverse events were mild and unrelated to sebelipase alfa. Infusion-related reactions were uncommon, mild and gastrointestinal in nature (diarrhea, abdominal cramping). No anti-drug antibodies have been detected and no drug-related serious adverse events have been reported in this study to date. Two serious adverse events (cholecystitis/cholelithiasis) considered unlikely related to sebelipase alfa occurred in one patient and this patient continues treatment with sebelipase alfa in the study.
Clinical manifestations of LAL Deficiency presenting in children and adultsA poster described the results from an observational study designed to characterize the clinical presentation and progression of LAL Deficiency presenting in children and adults. The study consisted of a retrospective chart review and a single prospective evaluation. Forty-eight patients with a confirmed diagnosis of LAL Deficiency enrolled in the study. Results from the multinational study indicate that most LAL Deficiency cases were diagnosed as children (median age at diagnosis 9.5 years; range 1.2 to 46.1 years). Elevated serum transaminases (ALT and AST) and LDL cholesterol levels were common, persistent, and frequently present from early childhood. A majority of patients (44/48) had ALT above the age and gender-specific upper limit of normal at the first recorded value. Six of 48 patients required a liver transplant, including four patients who required a liver transplant before 18 years of age. Only nine patients identified were over the age of 40 and two of these nine patients required liver transplantation. Of the 31 patients who had a liver biopsy performed, steatosis, fibrosis, and cirrhosis were documented in 27 (87%), 16 (52%), and 5 (16%) patients, respectively. Despite the use of lipid lowering therapy (median age at initiation was 11.3 years), dyslipidemia persisted, and LDL values remained elevated (>150mg/dl) from early childhood at multiple time points in a high proportion of patients. Most LDL values (270/306) were greater than 100 mg/dL. Twenty-seven of 48 patients had at least one LDL value of greater than 100 mg/dL while receiving lipid lowering therapy. Sebelipase alfa for LAL Deficiency LAL Deficiency is a rare autosomal recessive lysosomal storage disease (LSD) caused by a marked decrease in LAL enzyme activity. LAL Deficiency presenting in children and adults, historically called Cholesteryl Ester Storage Disease (CESD), is an underappreciated cause of cirrhosis and accelerated atherosclerosis. These complications are due to the buildup of fatty material in the liver, blood vessel walls and other tissues as a result of the decreased LAL enzyme activity. Infants presenting with LAL Deficiency, historically called Wolman disease, show very rapid progression with death, usually in the first six months of life. Affected infants develop severe malabsorption, growth failure and liver complications. Sebelipase alfa (SBC-102) is a recombinant form of the human LAL enzyme being developed by Synageva as an enzyme replacement therapy for LAL Deficiency. Synageva is evaluating sebelipase alfa in global Phase 3 clinical trials in infants, children and adults with LAL Deficiency. Sebelipase alfa has been granted orphan designation by the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the Japanese Ministry of Health, Labour and Welfare. Additionally, sebelipase alfa received fast track designation by the FDA, and Breakthrough Therapy designation by the FDA for LAL Deficiency presenting in infants. SBC-103 for MPS IIIB The mucopolysaccharidoses (MPS) consist of a group of rare LSDs caused by a deficiency of enzymes needed to break down complex sugars called glycosaminoglycans. The MPS III syndromes (also known as Sanfilippo syndromes) share complications with other MPS diseases but represent a clinically distinct subset with marked central nervous system degeneration. Mucopolysaccharidosis IIIB (MPS IIIB, also known as Sanfilippo B syndrome) is caused by a decrease in alpha-N-acetyl-glucosaminidase (NAGLU) enzyme activity which leads to the buildup of abnormal amounts of heparan sulfates (HS) in the brain and other organs. The accumulation of abnormal HS, particularly in the central nervous system, leads to severe cognitive decline, behavioral problems, speech loss, increasing loss of mobility, and premature death. SBC-103 is a recombinant form of the human NAGLU enzyme being developed by Synageva as an enzyme replacement therapy for MPS IIIB. Using various dosing approaches, SBC-103 reduced HS substrate storage in the brain, liver and kidney in an MPS IIIB animal model. SBC-103 has been granted orphan designation by the FDA and the EMA. Synageva’s additional pipeline programs and manufacturing platform Synageva’s additional pipeline programs include other proteins targeting rare diseases at various stages of preclinical development. These diseases are characterized by significant morbidity and mortality and these programs are selected based on scientific rationale, high unmet medical need, potential to impact disease course and strategic alignment with the company’s corporate focus. In addition to these novel pipeline programs, Synageva is leveraging its manufacturing platform to develop improved biologic therapies for diseases with high unmet medical need.
Synageva’s proprietary manufacturing platform utilizes technology to produce drug product with consistent characteristics that enable robustness and flexibility during scale-up. In addition, the platform can provide favorable structural properties for bio-distribution and cell targeting in comparison to glycoproteins produced from other sources.Synageva routinely posts information that may be important to investors in the “Investor Relations” section of the company’s web site at www.synageva.com. Synageva encourages investors and potential investors to consult this web site regularly for important information about the company. Further information regarding Synageva BioPharma Corp. is available at www.synageva.com. Forward-Looking Statements This news release contains “forward-looking statements”. Such statements generally can be identified by the use of words such as “anticipate,” “expect,” “plan,” “could,” “intend,” “believe,” “may,” “will,” “estimate,” “forecast,” “project,” or words of similar meaning. These forward-looking statements address, among other matters, the potential of sebelipase alfa, our plans for leveraging our manufacturing platform to advance our pipeline programs and develop improved biologic therapies, and our belief that our platform can provide favorable structural properties for bio-distribution and cell targeting in comparison to glycoproteins produced from other sources. Many factors may cause actual results to differ materially from those expressed or implied by forward-looking statements, including inaccurate assumptions and a broad variety of risks and uncertainties, including, risk of delays in completing our clinical trials, risk that the outcomes of our clinical trials may not support registration or further development of our product candidates due to safety, efficacy or other reasons, the content and timing of decisions by the U.S. Food and Drug Administration and other regulatory authorities, the ability to maintain the current favorable protein structural properties for bio-distribution and cell targeting as compared to glycoproteins produced from other sources, and the risks identified under the heading “Risk Factors” in Synageva’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (the “SEC”) on November 4, 2013 and other filings Synageva periodically makes with the SEC, and others of which are not known. Further analyses of the data described in this press release may lead to different (including less favorable) interpretations of the data. Clinical trial data are subject to differing interpretations, and regulatory agencies, as well as medical and scientific experts, may not share the Synageva’s views regarding this data or its implications. Synageva may encounter problems or delays in clinical development and regulatory approval process. No forward-looking statement is a guarantee of future results or events, and investors should avoid placing undue reliance on such statements. Synageva undertakes no obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. Our business is subject to substantial risks and uncertainties, including those referenced above.
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