Synageva BioPharma Corp. (Synageva) has announced that the US Food and Drug Administration (FDA) granted Breakthrough Therapy designation to sebelipase alfa for the treatment of early onset lysosomal acid lipase deficiency (LAL deficiency), also known as Wolman disease.

The designation was based on data generated from clinical trials with sebelipase alfa in patients with early onset LAL deficiency. The FDA also confirmed that late onset LAL deficiency is "a serious and life threatening disease or condition" and that Breakthrough Therapy designation could be obtained for this aspect of the disease with additional clinical information.

According to the FDA, Breakthrough Therapy designation is intended to expedite the development and review of drugs for serious or life-threatening conditions. The criteria for Breakthrough Therapy designation require preliminary clinical evidence that demonstrates the drug may have substantial improvement on at least one clinically significant endpoint over available therapy. A Breakthrough Therapy designation conveys all of the fast track program features, as well as more intensive FDA guidance on an efficient drug development programme.

"We are pleased that the FDA designated sebelipase alfa as Breakthrough Therapy for patients with early onset LAL deficiency, or Wolman disease," said Anthony Quinn, senior vice president and chief medical officer of Synageva. "We are deeply aware of the devastating impact this disease has on infants who often die within the first six months of life because of this disease. Our ongoing phase 2/3 trial delivers hope for these infants and their families. We continue to progress site activation and patient enrollment in both this trial and the global phase 3 ARISE trial in children and adults, and look forward to working closely with the FDA to support approval of the drug in an efficient manner."

LAL deficiency is a rare autosomal recessive lysosomal storage disorder (LSD) caused by a marked decrease in LAL enzyme activity. Late onset LAL deficiency, sometimes called Cholesteryl Ester Storage Disease (CESD), is an underappreciated cause of cirrhosis and accelerated atherosclerosis in children and adults. These complications are due to the buildup of fatty material in the liver and blood vessel walls as a result of decreased LAL enzyme activity. Early onset LAL deficiency, sometimes called Wolman disease, is the most rapidly progressive form of LAL Deficiency and is usually fatal within the first six months of life. Affected infants develop severe malabsorption, growth failure and liver failure. There are no approved therapies for LAL deficiency.

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. Synageva is evaluating sebelipase alfa in global clinical trials for both early and late onset LAL deficiency. Sebelipase alfa has been granted orphan designation by the 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 early onset LAL Deficiency.

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 marked decrease in alpha-N-acetyl-glucosaminidase (NAGLU) enzyme activity which leads to the buildup of abnormal sugars called heparan sulfate disaccharides (HSD) in the brain and other organs. The accumulation of abnormal HSD, particularly in the central nervous system, leads to severe cognitive decline, behavioral problems, speech loss, increasing loss of mobility, and premature death. There are no approved therapies for MPS IIIB.

SBC-103 is a recombinant form of the human NAGLU enzyme under development by Synageva as an enzyme replacement therapy for MPS IIIB. Using various dosing approaches, SBC-103 reduced HSD substrate storage in the brains, liver and kidney tissues in an MPS IIIB animal model. SBC-103 has been granted orphan designation by the FDA and the EMA. Synageva plans to enter SBC-103 into human clinical trials for MPS IIIB during the first half of 2014.

Synageva is a biopharmaceutical company focused on the discovery, development, and commercialization of therapeutic products for patients with life-threatening rare diseases and unmet medical need.