Late Onset LAL Deficiency (CESD) Literature Review Published in the Journal of Hepatology

Late Onset LAL Deficiency (CESD) Literature Review Published in the Journal of Hepatology

LEXINGTON, Mass.--(BUSINESS WIRE)-- Synageva BioPharma Corp. (Synageva) (NAS: GEVA) , a clinical stage biopharmaceutical company developing therapeutic products for rare diseases, announced the publication of an article by Bernstein et al entitled, "Cholesteryl Ester Storage Disease: Review of the Findings in 135 Reported Patients with an Under-Diagnosed Disease" in the online version and an upcoming print edition of the Journal of Hepatology.

"We performed the most comprehensive review and analysis of late onset LAL Deficiency, or cholesteryl ester storage disease, cases found in the literature," said Donna Bernstein, MS, CGC, the lead author and a genetic counselor in the Division of Medical Genetics, Director of the Lysosomal Storage Disease Program at North Shore-Long Island Jewish Health System. "Based on this review, we found that the abnormal fat accumulation in liver cells, adrenal glands, intestines, and macrophages due to LAL Deficiency can lead to cirrhosis, high LDL, low HDL, accelerated atherosclerosis, and early demise," said Robert J. Desnick, MD, PhD, senior author of the study and Dean for Genetic and Genomic Medicine, Professor and Chairman Emeritus, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai Hospital. "LAL Deficiency may present in infancy, childhood, or adulthood but because the diagnosis is challenging, it is likely that many adult CESD patients, in particular, are being misclassified as having NAFLD, NASH, unexplained liver disease, familial hypercholesterolemia, or remain undiagnosed before succumbing to liver failure, stroke, myocardial infarction, or sudden death."

About the late onset LAL Deficiency literature review

The literature review included 135 cases found in the published scientific literature for whom clinical information was reported. The median age of earliest symptom onset and/or diagnosis of the cases reviewed was 5 years (range from birth to 68 years), with greater than 80% experiencing symptom and/or disease onset by 12 years of age. The review excluded patients diagnosed with early onset LAL Deficiency (or Wolman disease) who died in the first year of life.

Liver dysfunction and/or failure occurred in all 135 patients, including hepatomegaly in 99% of patients and elevated transaminases in all cases reporting serum transaminase activities. Of the 112 biopsied patients, 64% had fibrosis and/or cirrhosis. Seventeen patients required a liver transplant and/or died as a result of their liver failure, including nine patients who underwent a liver transplant at 5-14 years of age. Twelve patients had esophageal varices including nine who were 5-20 years of age at the time of the event. When reported, most patients had elevated LDL and decreased HDL. Total cholesterol was elevated in all 110 patients for whom it was reported, and of the 43 patients in whom serum LDL-cholesterol was reported, 79% had elevated levels (>200 mg/dL) despite 49% of these patients being treated with statins. In the 65 patients for whom HDL-cholesterol levels were reported, 88% had HDL-cholesterol levels less than or equal to 40 mg/dL.

"This comprehensive literature review underscores our understanding that late onset LAL Deficiency, or CESD, is a progressive disease with severe liver and cardiovascular complications which can occur as early as the first and second decade of life," said Anthony Quinn, MBChB, PhD, FRCP, Senior Vice President and Chief Medical Officer of Synageva. "With the global ARISE Phase 3 trial of sebelipase alfa now underway in children and adults with LAL Deficiency, it is important that we continue to raise awareness of this underappreciated cause of cirrhosis and accelerated atherosclerosis."

About Synageva's Lead Program

Sebelipase alfa (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 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 and blood vessel walls may lead to liver cirrhosis, liver failure and accelerated atherosclerosis. 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 Synageva BioPharma Corp.

Synageva is a clinical stage biopharmaceutical company focused on the 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 a team with a proven record of bringing therapies to patients with rare diseases.

Dr. Desnick is a consultant for Synageva and serves as a member of its Scientific Advisory Board.

Further information regarding Synageva BioPharma Corp. is available at

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 manner in which LAL Deficiency presents in different patient groups and how the disease may be misclassified as other diseases. 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 our ability to help the medical community improve its diagnosis of LAL Deficiency and those identified under the heading "Risk Factors" in the Company's Annual Report on Form 10-K filed with the Securities and Exchange Commission (the "SEC") on March 14, 2013, and other filings Synageva periodically makes with the SEC, and others of which are not known. 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. Investors, potential investors, and others should give careful consideration to these risks and uncertainties.

"Dedicated to Rare Diseases®" is a registered trademark and "Synageva BioPharma™" is a trademark of Synageva BioPharma Corp.

Synageva BioPharma Corp.
Matthew Osborne, 781-357-9947

KEYWORDS: United States North America Massachusetts


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