Multiple Sclerosis
Natalizumab Re-approved for Relapsing Multiple Sclerosis
Jun 9, 2006 - 12:09:37 AM

U.S. Food and Drug Administration (FDA) has approved the supplemental Biologics License Application (sBLA) for the reintroduction of Natalizumab as a monotherapy treatment for relapsing forms of multiple sclerosis (MS) to slow the progression of disability and reduce the frequency of clinical relapses. The approval for reintroduction was granted based on the review of Natalizumab clinical trial data; revised labelling with enhanced safety warnings; and a risk management plan, called TOUCH Prescribing Program, designed to inform physicians and patients of the benefits and risks of Natalizumab treatment and minimize potential risk of progressive multifocal leukoencephalopathy (PML). The reintroduction of Natalizumab offers new hope as an important therapeutic choice for patients living with this disabling disease. "Natalizumab has demonstrated compelling efficacy in MS, and we believe the TOUCH Prescribing Program, designed in collaboration with the FDA, will help patients and physicians assess the benefits and risks of Natalizumab and make informed decisions about therapy," said James C. Mullen, Chief Executive Officer, Biogen Idec.

"We are pleased with the FDA's decision to once again make Natalizumab available to patients and their families suffering from this chronic, debilitating disease, " said Kelly Martin, Chief Executive Officer, Elan. "There continues to be a significant unmet medical need where Natalizumab will be an important treatment option. "

Today's action follows a March 8, 2006 unanimous recommendation by the FDA's Peripheral and Central Nervous System Drugs Advisory Committee to allow the reintroduction of Natalizumab. TOUCH (TYSABRI® [Natalizumab] Outreach: Unified Commitment to Health) Prescribing Program was developed in conjunction with the FDA to facilitate the appropriate use of Natalizumab and to assess, on an ongoing basis, the incidence and risk factors for PML and other serious opportunistic infections associated with Natalizumab treatment. This program represents Biogen Idec and Elan's commitment to making the unique benefits of Natalizumab available in a responsible manner. Elements of the TOUCH Prescribing Program include revised labeling with a prominent boxed warning of the risk of PML; and warnings against concurrent use of Natalizumab with chronic immunosuppressant or immunomodulatory therapies, and patients who are immunocompromised due to HIV, hematological malignancies, organ transplants or immunosuppressive therapies, mandatory enrolment for all prescribers, central pharmacies, infusion centres and patients who wish to prescribe, distribute, infuse, or receive, respectively, Natalizumab; controlled, centralized distribution only to authorized infusion centers, mandatory FDA-reviewed educational tools for patients and physicians, including a patient medication guide, TOUCH enrollment form and a monthly pre-infusion checklist, ongoing assessment of PML risk and overall safety, a 5,000 patient cohort observational study over five years, the Natalizumab Global Observation Program in Safety (TYGRIS)

Natalizumab treatment also resulted in sustained and statistically significant reductions in brain lesion activity as measured by MRI. The two-year data from the SENTINEL add-on trial also demonstrated that treatment with Natalizumab in addition to AVONEX® (Interferon beta-1a) had a significant effect on disability progression, relapse rate and brain MRI disease activity compared to AVONEX alone.

Natalizumab increases the risk of PML, an opportunistic viral infection of the brain that usually leads to death or severe disability. Three cases of PML occurred in clinical trial patients who were concomitantly exposed to immunomodulators (interferon beta in the patients with MS) or were immunocompromised due to recent treatment with immunosuppressants (e.g., azathioprine in the patient with Crohn's disease). A third case of PML occurred among 1,043 patients with Crohn's disease after the patient received eight doses. The number of cases is too few and the number of patients treated too small to reliably conclude that the risk of PML is lower in patients treated with Natalizumab alone than in patients who are receiving other drugs that decrease immune function or who are otherwise immunocompromised. Healthcare professionals should monitor patients on Natalizumab for any new signs or symptoms that may be suggestive of PML. Natalizumab dosing should be withheld immediately at the first sign or symptom suggestive of PML.

Natalizumab is contraindicated in patients who have or have had PML or with known hypersensitivity to Natalizumab or any of its components. In Phase III placebo-controlled trials of Natalizumab in MS, the overall incidence and rate of other infections were balanced between Natalizumab-treated patients and controls. Herpes infections were slightly more common in patients treated with Natalizumab. Commonly reported infections with Natalizumab included urinary tract infections, lower respiratory tract infections, gastroenteritis and vaginitis. Serious opportunistic and other atypical infections have been observed in Natalizumab-treated patients, some of these patients were receiving concurrent immunosuppressants.

Serious events that occurred in Natalizumab-treated patients included hypersensitivity reactions (e.g., anaphylaxis), depression and gallstones. Appendicitis was more common in patients receiving Natalizumab with AVONEX. Common adverse events reported in Natalizumab-treated patients include infusion reactions, headache, fatigue, joint and limb pain, abdominal discomfort, diarrhoea and rash.

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