Privigen(R) Shows No Neurological Side Effects Compared with Currently Use 10/11/2007 19:00:00 Business Wire CSL Behring announced new data today that demonstrates that L-proline causes no neurological effects, including convulsive behaviour and spatial learning and memory, even at high doses, when compared with glycine, which is used in many current intravenous immunoglobulin (IVIg) products.
L-proline is used as stabilizer in the new Immune Globulin Intravenous (human) 10% product (Privigen(R)).
The data were presented at the American Congress of Allergy, Asthma and Immunology (ACAAI) in Dallas, Texas.
The study aimed to assess the neurological safety of glycine and L-proline in two separate tests using rats.
The neurobiological state was evaluated using the Irwin test, which assesses autonomic and sensorimotor functions, convulsive behaviour, and neurological side effects of drug administration.
Spatial learning and memory were assessed using the Morris water maze task.
The Irwin test assessed the neurobiological state and convulsive behaviour of adult rats, upon daily intravenous infusion with doses of glycine or L-proline corresponding to IVIg doses of approximately two and five g IgG/kg bodyweight, over five days.
This represents a multiple of the maximal dose applied to patients.
It was found that L-proline did not significantly affect behaviour or any of the measured neurological parameters neither during nor after infusion when compared to the saline vehicle control.
In comparison, rats infused with glycine showed behavioural changes including a significant decrease in spontaneous activity, decreased central nervous system (CNS) excitability and altered autonomic parameters.
Commenting on the data, CSL Behring lead researcher, Ulrich Kronthaler, PhD, said, “This data provides evidence of a neurological benefit when using L-proline, a naturally occurring amino acid stabilizer, over the currently used additives, such as glycine.” The Morris water maze test assessed the spatial learning and memory in rats, which had been treated with glycine or L-proline as newborns with dosing schemes relevant for IVIg applications at the potentially most vulnerable phase of their brain development.
The findings showed that no signs of acute neurotoxicity occurred during the treatment phase of the young rats and that as adults, their learning and memory abilities remained unimpaired.
IVIgs are used to treat several conditions, including immunodeficiencies and autoimmune diseases.
IVIG solutions are often formulated with glycine, but such solutions are not stable for extended time at room temperature.
The use of L-proline (250 mmol/L) at pH 4.8 has recently been demonstrated to allow storage of Privigen for at least three years at room temperature.
In July 2007, the U.S.
Food and Drug Administration (FDA) granted marketing approval to CSL Behring for Privigen, an intravenous immunoglobulin (IVIg), for treating patients diagnosed with primary immunodeficiency (PI) and chronic immune thrombocytopenic purpura (ITP).
CSL Behring plans to launch Privigen in the first quarter of 2008.
The application is currently under review by European and Swiss Regulatory Authorities.
Important Safety Information In clinical studies, Privigen has been shown to be safe.
As with any medication, side effects may accompany treatment.
The frequency of side effects was based on a review of 1,038 injections given during the clinical trial in the United States and Europe.
Because Privigen is made from plasma, as are all commercial human polyvalent immunoglobulins, the risk of transmitting infectious agents, including viruses, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent, cannot be completely eliminated.
Privigen is contraindicated in patients with known anaphylactic or severe hypersensitivity responses to Immune Globulin (Human).
Patients with severe selective IgA deficiency (IgA less than 0.05 g/L) may develop anti-IgA antibodies that can result in a severe anaphylactic reaction.
Such patients should only receive intravenous immune globulin with utmost caution and in a setting where supportive care is available for treating life-threatening reactions.
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