Pacira Pharmaceuticals has disclosed that it will end production of its lymphoma treatment DepoCyt® (cytarabine liposome injection) due to undisclosed manufacturing problems.
Pacira cited “persistent technical issues specific to the DepoCyt(e) manufacturing process” in a regulatory filing yesterday. The company said its decision did not affect any treatments that had already been distributed to customers or administered to patients.
As a result of its decision, Pacira said, it will incur a $5 million charge against second-quarter earnings related to the end of DepoCyt production. Half of the charge relates to writing off assets, $2 million to lease costs less estimated potential sublease income, and the remaining $0.5 million, to employee severance and other exit costs.
DepoCyt is a sustained-release liposomal formulation of the chemotherapeutic agent cytarabine that uses the company’s DepoFoam drug delivery technology. DepoFoam consists of microscopic spherical particles composed of a honeycomb-like structure of numerous internal aqueous chambers containing an active drug ingredient. Each chamber is separated from adjacent chambers by lipid membranes. Following injection, the DepoFoam particles release drug over an extended time by erosion and/or reorganization of the particles’ lipid membranes.
DepoCyt was granted accelerated approval in 1999 and full approval in 2007 by the FDA in the U.S., where it is indicated for the intrathecal treatment of lymphomatous meningitis. According to the Lymphoma Research Foundation, the condition is commonly treated by DepoCyt as well as by the chemotherapy agent methotrexate, also sold under the brands Otrexup™ (by Antares Pharma), Rasuvo® (Medac Pharma), Rheumatrex® (Stada Pharmaceuticals), and Trexall™ (Teva Pharmaceutical Industries).
“Treatment for secondary leukemic and lymphomatous meningitis remains unsatisfactory, and efforts should be made to prevent and treat subclinical disease,” Ernesto Ayala, M.D., of Moffitt Cancer Center, and colleagues concluded in a review of medical literature published earlier this year in the journal Cancer Control. “Once leukemic and lymphomatous meningitis has developed, treatment is palliative in most patients, with few surviving the disease long-term.”
Pacira manufactures DepoCyt in San Diego, in a 22,000-square-foot facility known as Building 6 that houses the current manufacturing process for DepoCyt(e), the fill/finish of DepoCyt(e) into vials, a pilot plant suite for new product development and early-stage clinical product production, a microbiology laboratory, and miscellaneous support and maintenance areas.
In 2012, Pacira temporarily ceased manufacturing of DepoCyt for sale in the EU to correct manufacturing issues noted in an inspection report by the U.K.’s Medicines & Healthcare products Regulatory Agency (MHRA) in July 2012 regarding its manufacturing facility. The report called for a selective recall of DepoCyte in EU member states where DepoCyte was not considered an “essential medicinal product,” which helped lower product sales that year. MHRA allowed production to resume in January 2013.
Last year, Pacira recognized $7.2 million in revenue from commercial partners related to DepoCyt. Leadiant Biosciences (which in December changed its name from Sigma-Tau Pharmaceuticals) markets DepoCyt in the U.S., where it handles handles supply and distribution of the drug, while Mundipharma International markets the product under the name DepoCyte in the EU and selected other European countries.
Mundipharma began distributing DepoCyt in Europe in 2003, and in 2014 agreed with Pacira to extend their agreement 15 years, to 2033, in return for Mundipharma paying Pacira $8 million upfront.