Another highly purified IVIG to hit the market
Another highly purified IVIG to hit the market
Bayer Biological Products was given Food & Drug Administration approval last month for a new intravenous immune globulin (IVIG) product. Gamunex is the first new (from start to finish) IVIG product to hit the market in more than 10 years, Bayer claims.
You may recall a few years back there was a shortage of IVIGs, which was a result of several factors that just happened to coincide. New, stricter regulations for the purification of IVIGs led to product recalls. Demand for IVIGs increased as clinicians began experimenting with them in several disorders. At the same time, there was a dip in supply caused by a drop in plasma donations (IVIG is derived from donated human plasma).
Since the IVIG shortage in the late 1990s, IVIG manufacturers have taken steps to prevent future shortages. ZLB Bioplasma, for instance, purchased 47 plasma centers across the United States to help ensure a supply of immune globulins.
It was the shortage that sparked Bayer's plan to create a brand-new IVIG product. "This really went back to the drawing board," said Tricia McKernan, director of public policy and communications for Bayer. Researchers at the company were challenged to create the ideal IVIG product by starting from square one. Now, Bayer has a new plant in Clayton, N.C., devoted to producing Gamunex. The product is purified differently from currently marketed IVIGs.
The new purification process uses caprylate, a fatty acid that inactivates enveloped viruses. The enveloped viruses, such as HIV, West Nile, and hepatitis B and C, are of particular concern with donated plasma. In fact, during the early 1990s, there were cases of hepatitis C transmission due to IVIG. Since then, it should be noted, all manufacturers of IVIGs have added purification steps targeted at theses viruses.
The purification of Gamunex replaces the solvent-detergent method used in the previous process (for Gamimune, Bayer's original IVIG product), and it decreases exposure to ethanol. The new product remains in liquid phase throughout the process. Nonenveloped viruses, such as hepatitis A, are removed through anion exchange chromatography and two filtration steps, said McKernan. These steps also remove prions that can cause encephalopathic diseases such as Creutzfeldt-Jakob disease.
In addition, Gamunex is incubated at low pH, resulting in a more stable product and coincidentally providing one more way to inactivate viruses. Because the purification process has been streamlined, the time to completion has been reduced from 100 hours to 36. Bayer researchers believe all of this preserves biological activity, although there are no hard data on this yet.
"Gamunex really is a much more gentle treatment," said Erwin Gelfand, M.D., chairman of the department of pediatrics at the Jewish Medical and Research Center in Denver. "It contains no sugar, virtually no salt, and is a very physiologically compatible formulation." He believes Bayer's new manufacturing process produces a higher quality, better yield IVIG.
Bayer received FDA approval for Gamunex based on favorable results of clinical trials. In a study of the IVIG in patients with primary immunodeficiency (PI), Gamunex was pitted against Bayer's original IVIG, Gamimune N. The study was designed to prove that Gamunex was as safe and efficacious as Gamimune. The results indicate Gamimune may be a bit more effective. "The incidence of validated sinopulmonary infections was significantly lower," said McKernan. That is, there were nine (12%) infections with Gamunex and 17 (23%) with Gamimune. The incidence of nonvalidated infections, however, was about the same with both drugs (77% and 78%, respectively).
During clinical trials, no thrombosis or kidney problems were observed. Both of these adverse effects have been a problem with some older IVIGs. The renal damage associated with IVIGs has been attributed to the sucrose added to certain products. Because immune globulins are most stable at lower pH, sucrose is sometimes added to maintain stability and consequently reduce side effects. Newer IVIGs, such as ZLB's Carimune and Carimune NF and Bayer's Gamunex, are stabilized through newer production methods and do not contain sucrose. Glycine is added to Gamunex as a stabilizer.
Gamunex is indicated for treatment of PI and idiopathic thrombocytopenia purpura (ITP). People with PI lack their own immune globulins and require injections of IVIG in order to fight off infections. People with ITP tend to have low platelet counts, which can lead to bleeding.
There has been a lot of speculation about the use of IVIGs to treat other disorders. Off-label uses are most commonly for autoimmune diseases and neurologic disorders. Gelfand admitted researchers still don't know why IVIGs are effective in treating some of these diseases, but theories abound. He has observed that if IVIGs are effective, positive effects are seen soon after treatment, and fewer adverse effects occur than with cytotoxic agents or corticosteroids. Bayer has already begun trials to test Gamunex in people with multiple sclerosis and chronic inflammatory demyelinating polyneuropathy (CIDP).
Jillene Lewis, R.Ph.
The AUTHOR is a medical writer based in the Seattle area.
TIPS TO REMEMBER: Gamunex
- Gamunex is indicated for primary immunodeficiency (PI) and for idiopathic thrombocytopenic purpura (ITP).
- Gamunex is contraindicated in patients allergic to IVIGs and should be used with extreme caution in people with antibodies to immunoglobulin A (IgA).
- Gamunex should be administered with caution in patients at risk for renal failure, such as the elderly and people with diabetes, sepsis, or preexisting renal disease.
- Gamunex vials are for single use only.
Jillene Lewis. Another highly purified IVIG to hit the market. Drug Topics Oct. 20, 2003;147:HSE6.