Synageva BioPharma Corp. announced that the U.S. 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. 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 program. Synageva's lead programs sebelipase alfa for LAL Deficiency and SBC-103 for MPS IIIB: 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 BioPharma Corp. reported 12-month results from an ongoing extension study with sebelipase alfa in adults with late onset Lysosomal Acid Lipase (LAL) Deficiency. The data will be presented by Reena Sharma, M.D., Consultant, Adult Inherited Metabolic Diseases, Salford Royal Hospital, U.K., during an oral presentation at the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) annual meeting being held in London, U.K., May 8-11, 2013. Nine adults with LAL Deficiency enrolled in the Phase 1/2 trial. After completing the initial four-week portion of the trial, patients were allowed to continue treatment with sebelipase alfa as part of a long-term, open-label extension study. Eight of nine patients enrolled in the extension study and six of these eight have now completed the first 12 months of the study. At one year, the effects of sebelipase alfa in this study were sustained as compared to the effects at nine months. Sebelipase alfa continues to provide evidence of a reduction in liver damage with sustained reductions in both ALT and AST, frequently into the normal range. Sebelipase alfa produced mean percent decreases for ALT and AST from the initial baseline to month 12 of the extension study of 56% and 40%, respectively (p=0.031 for both comparisons). In addition, sebelipase alfa maintained the improvements in the dyslipidemia associated with LAL Deficiency as measured by mean percent decreases from the initial baseline to month 12 of the extension study for LDL-C of 63% (p=0.031), total cholesterol of 42% (p=0.031), triglycerides of 47% (p=0.031), as well as a mean increase in HDL of 29% (p=0.031). Sebelipase alfa was generally well tolerated throughout the initial 12 months of the extension study. The majority of adverse events were mild and unrelated to sebelipase alfa. Infusion-related reactions were uncommon and the majority were gastrointestinal (diarrhea, abdominal cramping) events of mild severity. One patient with a moderate (Grade 2) allergic type infusion-related reaction, who paused treatment with sebelipase alfa at nine months of the extension study, remains off treatment with further tests pending. No anti-drug antibodies have been detected in any subjects tested to date in either the initial portion or extension portion of the Phase 1/2 study. A single patient during the extension study developed acute cholecystitis and cholelithiasis (two serious adverse events) which were later treated with elective cholecystectomy. These two serious adverse events were considered unlikely related to sebelipase alfa. This patient continues treatment with sebelipase alfa without a change in dosing and administration.

Synageva BioPharma Corp. reported unaudited consolidated earnings results for the first quarter ended March 31, 2013. For the quarter ended March 31, 2013, the company reported a net loss of $14.5 million or $0.54 per basic and diluted share compared to a net loss of $7.4 million or $0.35 per basic and diluted share for the corresponding quarter of the prior year. Revenue of $5.1 million consists of $1.7 million of Fuzeon royalties from Roche, as well as $3.4 million from the company's collaboration agreements against $2.4 million a year ago. Loss from operations was $14.6 million against $7.4 million a year ago. The company reiterated its previous net operating loss guidance of between $87 million and $97 million for 2013. The net loss is primarily due to investments necessary to support global clinical development of the lead program sebelipase alfa, further development of SBC-103, expansion of the global clinical, medical affairs and commercial infrastructure, expansion of manufacturing capabilities, as well as advancement of other pipeline programs. The company plans to enter SBC-103 into human clinical trials for MPS IIIB during the first half of 2014.