Late Onset LAL Deficiency (CESD) Literature Review Published in the Journal
LEXINGTON, Mass. -- March 26, 2013
Synageva BioPharma Corp. (Synageva) (NASDAQ: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
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
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
“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
Press spacebar to pause and continue. Press esc to stop.