Natalizumab

NABILONE NAFAZAIR NAFCIL NAGANOL NAGLAZYME NALFED NALFON NALPHEN

Natalizumab

As of January 2008, in the USA natalizumab is perscribed for the treatment of multiple sclerosis and Crohn's disease; in the EU and several other countries worldwide (including Canada, Australia, etc), it is perscribed for the treatment of multiple sclerosis. TYSABRI was evaluated in two randomized, double-blind, placebo-controlled trials in patients with multiple sclerosis. Both studies enrolled patients who experienced at least one clinical relapse during the prior year and had a Kurtzke Expanded Disability Status Scale (EDSS) score between 0 and 5.0. The primary endpoint at 2 years was time to onset of sustained increase in disability, defined as an increase of at least 1 point on the EDSS from baseline EDSS ≥ 1.0 that was sustained for 12 weeks, or at least a 1.5 point increase on the EDSS from baseline EDSS=0 that was sustained for 12 weeks. Also in these trials natalizumab slowed the progression of disability (as measured by EDSS) by approximately 50% [3] (the US and EU medical authorities use slightly different measures of disability progression, and use values of between 42% and 54%). Only two of the interferons (glatiramer acetate or Copaxone, per it's FDA marketing label, has not achieved an indication for slowing the progression of disability.[4])have been shown to decrease the progression of disability, but again only by around 30%, a margin far surpassed by natalizumab. Two further randomized controlled trials have confirmed natalizumab's effectiveness in increasing the rate of remission and in maintaning remission in Crohn's. Investigators of one such trial found that "the substantial improvement in HRQoL experienced by patients who responded to natalizumab induction therapy was maintained during an additional 48 weeks of maintenance therapy". [12] "In multiple sclerosis, lesions are believed to occur when activated inflammatory cells, including T-lymphocytes, cross the blood-brain barrier (BBB). Leukocyte migration across the BBB involves interaction between adhesion molecules on inflammatory cells and their counterreceptors present on endothelial cells of the vessel wall. The clinical effect of natalizumab in multiple sclerosis may be secondary to blockade of the molecular interaction of α4β1-integrin expressed by inflammatory cells with VCAM-1 on vascular endothelial cells, and with CS-1 and/or osteopontin expressed by parenchymal cells in the brain. Data from an experimental autoimmune encephalitis animal model of multiple sclerosis demonstrate reduction of leukocyte migration into brain parenchyma and reduction of plaque formation detected by magnetic resonance imaging (MRI) following repeated administration of natalizumab. The clinical significance of these animal data is unknown". While the drug was shown to be powerfully effective for both preventing relapses of MS and for induction of and sustaining remission in Crohn's Disease, it was announced on February 28, 2005 that one fatal and one non-fatal case of a rare, often lethal brain disease known as progressive multifocal leukoencephalopathy (PML) were found in two patients given natalizumab in combination with interferon beta-1a (Avonex) over a two year period.[15][16] Natalizumab was voluntarily withdrawn from the market that day,[17] after the first two confirmed cases, so that an intensive safety evaluation could be conducted to determine the prevalence of PML and course of action. During the safety review, a second PML death was attributed to natalizumab in March of 2005, in a clinical trial Crohn’s disease patient who had died in December 2003 from what was thought at that time to be a brain tumor, but was subsequently re-evaluated as having been PML. The Crohn’s disease patient who had received eight doses of natalizumab over an 18-month period had a prior medication history which included multiple courses of immunosuppressant agents, which are thought to have contributed significantly to the PML.[18] They also included a special restricted distribution program known as the TOUCH Prescribing Program ("TOUCH" stands for "Tysabri Outreach: Unified Commitment to Health"). Under this program, only prescribers, infusion centers, and specialty pharmacies trained and enrolled in the TOUCH program can prescribe and administer Tysabri. Additionally, patients must also be enrolled in the TOUCH program,[21] so that they may be educated on Tysabri as well as periodically evaluated while being treated with Tysabri. In April of 2006 the Committee for Medicinal Products for Human Use (CHMP), the scientific committee of the European Medicines Agency (EMEA), issued a positive opinion recommending marketing authorization for natalizumab as a treatment for relapsing-remitting multiple sclerosis. Several weeks later on June 29, the EMEA also approved natalizumab in the European Union for relapsing forms of MS, but not subject to the TOUCH restrictions.[22] In recognition of the fact that the link of Tysabri to PML is unclear owing to the fact that all 3 incidences were in combination therapy with other immuno-modulating drugs, the US Food & Drugs Administration's Black Box label states: "Although the cases of PML were limited to patients with recent or concomitant exposure to immunomodulators or immunosuppressants, there were too few cases to rule out the possibility that PML may occur with TYSABRI monotherapy"[23] The wholesale price of Tysabri is US$2184.62 per vial. Given that natalizumab is generally administered 13 times a year, the annual costs for Tysabri is approximately US$28,400 (not including costs associated with infusion services), priced at a premium to the older generation drugs.

• natalizumab
• nebivolol
• nateglinide
• levetiracetam
• montelukast
• nitrendipil
• mometason
• moxifloxacin
• memantine
• levocetirizin
• lopinavir
• lercanidipin

Natalizumab

NABILONE NAFAZAIR NAFCIL NAGANOL NAGLAZYME NALFED NALFON NALPHEN NALSPAN NAMENDA NASCOBAL NATACYN NATALINS NATALIZUMAB NATAMYCIN NAVELBINE BACTOCILL BACTRAMYCIN CAFATINE CAFCIT CALCILAC CALCILEAN CALCIMAR CALCIONATE CALCIPARINE CANDESARTAN CAPITROL CAPOZIDE CAPSIN CAPTIMER CARBETOCIN ABARELIX ABATACEPT ABBOKINASE