Sigma-Tau Pharmaceuticals Announces Approval for New Manufacturing Process for ONCASPAR® (Pegaspargase) Primary Ingredient

- No Interruption in Production for Key Drug Used to Treat Acute Lymphoblastic Leukemia -

GAITHERSBURG, Md., April 18, 2011 /PRNewswire/ -- Sigma-Tau Pharmaceuticals, Inc. is pleased to announce that it has received approval from the U.S. Food and Drug Administration (FDA) to manufacture L-asparaginase, the primary ingredient in the oncology medicine ONCASPAR® (pegaspargase).  ONCASPAR is the only FDA-approved PEGylated formulation of L-asparaginase which is a key component in the treatment of acute lymphoblastic leukemia (ALL). The attempt to secure approval to manufacture L-asparaginase came after the previous supplier decided to cease production, leading to a three-year development effort to create a comparable active ingredient.  The approval averts a potentially dangerous drug shortage situation in the U.S. which could have affected thousands of patients with ALL.

"To get a complex biologic medicine such as this exactly right takes a great deal of work for both the manufacturer and the FDA," said Gregg Lapointe, Chief Executive Officer, Sigma-Tau Pharmaceuticals, Inc.  "We are pleased to announce that with this approval, there will be no interruption in either the production of the medicine or in the treatment of patients with ALL."

L-asparaginase is an enzyme that depletes the amino acid asparagine, which certain leukemic cells are dependent upon for survival.  L-asparaginase was first approved in 1978 as a treatment for ALL. In 1994, the FDA approved the PEGylated formulation of the medicine (ONCASAPR) which has the unique therapeutic advantages of sustained duration and prolonged effect over the native L-asparaginase, resulting in enhanced convenience for patients and providers.  ONCASPAR is given to patients with ALL as part of a multi-agent chemotherapeutic treatment regimen.  Administering L-asparaginase results in the depletion of asparagine circulating in the blood, which starves the leukemic cells and results in their death.  ONCASPAR was updated to first-line indication in 2006.

About Acute Lymphoblastic Leukemia (ALL):

Acute lymphoblastic leukemia (ALL) is a cancer of the white lymphoid blood cells, which when normal, fight infections.  It causes the body to produce abnormal and immature white blood cells that cannot accomplish this purpose.  ALL is the most common form of leukemia found in children, representing 23% of cancer diagnoses in children under age 15.  It occurs in one of every 29,000 children in the United States each year.  While ALL is most common in children, people can be diagnosed with ALL at any age and the risk increases after age 45.   Over the past 35 years, the overall five year survival rate for children with ALL has greatly improved, going from less than 5% in the 1960s to about 85% today.

About ONCASPAR® (pegaspargase):

ONCASPAR® (pegaspargase) is the only FDA-approved PEGylated formulation of L-asparaginase, the enzyme that depletes the amino acid asparagine.  For the last 25 years, L-asparaginase has been an important component in the treatment of acute lymphoblastic leukemia (ALL).

While normal cells can produce asparagine, leukemic cells are unable to produce enough asparagine to survive on their own. L-asparaginase is given to ALL patients to ensure depletion of asparagine that is circulating in the blood. Depletion (starving the leukemic cells) of asparagine ultimately results in leukemic cell death.

ONCASPAR allows patients to gain the full benefits of asparaginase therapy with enhanced patient convenience over native L-asparaginase (nonPEGylated form). Through the process of pegylation, the half-life of L-asparaginase is significantly increased and the L-asparaginase activity is sustained.

ONCASPAR can be administered through intramuscular (IM) injection or intravenous (IV) infusion. When utilized as a component of induction therapy for ALL, 1 dose of ONCASPAR achieved similar levels of asparagine depletion as 9 doses of native L-asparaginase.

The use of ONCASPAR for the treatment of ALL continues to be explored to evaluate the optimal duration of use.

ONCASPAR is indicated as a component of a multiagent chemotherapeutic regimen for the first-line treatment of patients with acute lymphoblastic leukemia (ALL) and for the treatment of patients with acute lymphoblastic leukemia and hypersensitivity to native forms of L-asparaginase.

ONCASPAR is contraindicated in patients with a history of serious allergic reactions to ONCASPAR, and in patients with a history of serious thrombosis, pancreatitis, or serious hemorrhagic events with prior L-asparaginase therapy.

ONCASPAR should be discontinued in the case of anaphylaxis or serious allergic reactions, thrombosis, or pancreatitis. Glucose intolerance, in some cases irreversible, can occur. Coagulopathy can occur. Perform appropriate monitoring.

The most common adverse reactions with ONCASPAR (>2%) are allergic reactions (including anaphylaxis), hyperglycemia, pancreatitis, central nervous system (CNS) thrombosis, coagulopathy, hyperbilirubinemia, and elevated transaminases.

In study 2 (n= 2770), the per-patient incidence for Grades 3 and 4 nonhematologic toxicities were: elevated transaminases (11%), coagulopathy (7%), hyperglycemia (5%), CNS thrombosis/hemorrhage (2%), pancreatitis (2%), clinical allergic reaction (1%), and hyperbilirubinemia (1%). There were 3 deaths due to pancreatitis.

*1 to 6 conversion of ONCASPAR to native L-asparaginase in other phases of treatment.

About Sigma-Tau Pharmaceuticals, Inc.:

Sigma-Tau Pharmaceuticals, Inc. is a U.S. based, wholly owned subsidiary of the sigma-tau Group, and is dedicated solely to the global development and commercialization of medicines for patients with rare diseases. Sigma-Tau Pharmaceuticals, Inc. is based in Gaithersburg, Maryland.  Since 1989, the company's products have been focused on rare diseases, including kidney disease, certain genetic disorders and cancers. With more than 7,000 identified rare diseases that affect approximately 25 million patients in the Unites States, Sigma-Tau places its considerable scientific resources behind the development and commercialization of compounds that benefit the few. The company has a substantial development program focused on transplant, cancer, inherited genetic disorders, malaria, and other areas of unmet medical need. For more information about the company, visit www.sigmatau.com.

SOURCE Sigma-Tau Pharmaceuticals