In September, the FDA approved 10 percent caprylate-chromatography purified immune globulin intravenous (IGIV-C), marketed as Gamunex, for treatment of chronic inflammatory demyelinating polyneuropathy (CIDP). This is the first IVIG therapy approved to treat any neurological disease in the US, experts said.
Manufactured by Talecris Biotherapeutics, the agent was designated an orphan drug by the FDA because CIDP affects fewer than 200,000 people in the US. CIDP, an autoimmune disorder resulting in progressive generalized limb weakness, areflexia, and large fiber sensory loss, affects two to seven individuals per 100,000 worldwide.
The results of the multicenter, multinational placebo-controlled clinical trial that secured FDA approval were published in the February Lancet Neurology. The study randomized 117 subjects with CIDP to IGIV or placebo and established the long-term safety and efficacy of IGIV. The agent was shown to reduce functional disability and significantly improved grip strength in CIDP patients.
For over two decades, IGIV has been used to treat CIDP and several other immune-mediated neuromuscular conditions such as Guillain-Barre syndrome, multifocal motor neuropathy, stiff-person syndrome, and more recently, myasthenia gravis, said Kenneth C. Gorson, MD, professor of neurology and a polyneuropathy researcher at St. Elizabeth's Medical Center and Tufts University School of Medicine in Boston, who was not involved in the Lancet Neurology study.
IGIV is generally very well tolerated, said Norman Latov, MD, one of the Lancet Neurology study investigators who is professor of neurology and neuroscience at Weill Medical College of Cornell University in New York City. He noted that occasionally patients may develop transient muscle aches, headache, or fever, and rarely, venous thromboses or renal failure in patients with pre-existing kidney disease.
IGIV contains antibodies purified from the blood plasma of thousands of healthy blood donors. It improves strength in patients with CIDP by modulating the inflammatory response that damages peripheral nerve myelin, most likely involving multiple mechanisms of action that include blocking Fc receptors and interfering with binding of pathogenic antibodies to various neuronal epitopes. However, the exact mechanisms of action responsible for the therapeutic effects remain unknown.
“The FDA approval probably will not have immediate effects on clinical practice,” said Dr. Gorson, because neurologists “will continue to use it for the neuromuscular diseases where it already has been shown to be effective based on clinical studies.” However, he added, the FDA labeling may help ensure that patients get health insurance coverage for the approved drug.
Insurance companies will not be able to cite the lack of FDA approval as a reason to deny reimbursement, agreed Peter Donofrio, MD, professor of medicine in the neurology department at Vanderbilt University, and member of the Steering Committee of Talecris for the Lancet Neurology study.
Prescribing IGIV for CIDP patients should be decided on an individual basis, said Drs. Donofrio and Gorson, contingent on clinical features of the illness, functional disability, and patient symptoms.
Carol Lee Koski, MD, medical director of the GBS/CIDP Foundation International and retired professor and director of the Neuromuscular Division at the University of Maryland School of Medicine, said she has prescribed IGIV for CIDP patients frequently as a first-line therapy. She prefers to use IGIV “in younger patients who are likely to be on treatment for several years and in older patients with comorbidities such as diabetes and osteoporosis.”
“Its chronic use is complicated by the expense and increasing pressure from third-party payers to use other less expensive drugs such as corticosteroids,” she said, but the FDA's approval “will allow physicians to select a drug for their CIDP patients that best suits their circumstances.”
• Hughes RA, Donofrio P, Bril V, et al., for the ICE Study Group. Intravenous immune globulin (10 percent caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study): a randomized, placebo-controlled trial. Lancet Neurol