Patients in the Phase I/II trial were predominantly male with a mean age of 32 years (range 19-45). Seven of nine patients had a history of hepatomegaly and/or splenomegaly, and two of nine patients had evidence of more advanced liver disease, including cirrhosis and portal hypertension. Seven patients had a history of other cardiovascular conditions. Seven of nine patients were receiving treatment with lipid modifying therapies including ezetimibe, statins, and other medications.For the seven patients with longer term dosing, sebelipase alfa produced mean decreases +/- SD for ALT and AST from the initial baseline to week 24 of the extension study of 48 +/- 21 U/L (54%) and 19 +/- 18 U/L (30%), respectively (p<0.05 for both). In addition, sebelipase alfa resulted in mean decreases from the initial baseline to week 24 of the extension study for total cholesterol of 69 +/- 52 mg/dL (31%), LDL-C of 62 +/- 36 mg/dL (43%) and triglycerides of 47 +/- 69 mg/dL (22%), p<0.05 for all measures, as well as mean increases in HDL of 4 +/- 5 mg/dL (14%) (p=0.09). Liver fat fraction was measured by multi-echo magnetic resonance imaging (MRI) or magnetic resonance spectroscopy (MRS) and liver volume was measured by MRI at the beginning of the extension study, at weeks 10/12, and at week 24 of the extension study. Treatment with sebelipase alfa resulted in a mean decrease in liver fat fraction of 34% and a mean decrease in liver volume of 8% at week 24. Sebelipase alfa was well tolerated throughout the initial six months of the extension study. The majority of adverse events were mild and unrelated to sebelipase alfa. Related or possibly related adverse events included headache, diarrhea, mild abdominal pain and cholesterol elevation. The majority of infusion-related reactions were gastrointestinal (diarrhea, abdominal cramping) and of mild severity. No antidrug antibodies were detected in any of the nine patients in the four week portion of the trial or in the seven patients tested in the extension study. A single patient during the extension study developed acute cholecystitis and cholelithiasis later treated with cholecystectomy. These two serious adverse events were considered by the investigator as unlikely related to sebelipase alfa.
Poster 1339 entitled “Enzyme Replacement with Recombinant Human Lysosomal Acid Lipase (rhLAL) in Patients with Cholesteryl Ester Storage Disease, the Late Onset Form of LAL Deficiency, Produces Sustained Decreases in Transaminases and Reduction in Liver Fat Content” can be viewed during the poster session on Monday, November 12, 2012 at 8:00 a.m.-5:30 p.m. EST.Additional sebelipase alfa data presented at the AASLD meeting Poster 1351 entitled “Recombinant Human Lysosomal Acid Lipase Decreases Hepatic Macrophage Aggregates and Colocalized Fibrosis in a Rat Model of Lysosomal Acid Lipase Deficiency” can be viewed during the poster session on Monday, November 12, 2012 at 8:00 a.m.-5:30 p.m. EST. The aim of this study was to further characterize the histopathological abnormalities associated with LAL Deficiency and to examine the effects of sebelipase alfa on liver fibrosis in the preclinical rat model. In this study, enzyme replacement with sebelipase alfa was associated with a marked reduction of fat in disease causing cells including macrophages and hepatocytes with an accompanying reduction in fibrosis relative to untreated LAL deficient animals. About Synageva’s Lead Program Sebelipase alfa 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 and 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 LSD 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, spleen and blood vessel walls leads to complications resulting in significant morbidity and mortality. 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. About Synageva BioPharma Corp. Synageva is a clinical stage biopharmaceutical company focused on the discovery, development, and anticipated 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.Forward-Looking Statements This news release contains “forward-looking statements” under the provisions of the Private Securities Litigation Reform Act of 1995. Such statements can be identified by introductory words such as “expects,” “plans,” “intends,” “believes,” “will,” “estimates,” “forecasts,” “projects,” or words of similar meaning and by the fact that they do not relate strictly to historical or current facts. Many factors may cause actual results to differ materially from forward-looking statements, including inaccurate assumptions and a broad variety of risks and uncertainties, some of which are known, including those identified under the heading “Risk Factors” in the Company’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (the “SEC”) on November 6, 2012, and other filings Synageva periodically makes with the SEC and others of which are not. Synageva cannot be sure when or if it will be permitted by regulatory agencies to undertake additional clinical trials or to commence any particular phase of clinical trials or how quickly patient enrollment in clinical trials will occur. In addition, early clinical results are not necessarily predictive of results that may be achieved from subsequent clinical trials. Because of this, statements regarding the expected timing of clinical trials or ultimate regulatory approval cannot be regarded as actual predictions of when Synageva will obtain regulatory approval for any phase of clinical trials or when it will obtain ultimate regulatory approval by a particular regulatory agency or when any of its drug product candidates might be commercialized. Synageva’s future financial results may differ from those currently anticipated due to a number of factors, including unanticipated costs in its research and development programs, fluctuations in royalty revenues and unplanned costs associated with maintaining and enforcing patents and other patent-related costs. 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.
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