Avonex®

After 15 years of follow-up, patients with relapsing-remitting multiple sclerosis (RRMS) who display disease activity despite treatment with interferon (IFN)β-1a tend to have unfavorable long-term outcomes, according to research published online Sept. 13 in the Annals of Neurology.

Robert A. Bermel, M.D., of the Cleveland Clinic, and colleagues conducted a multicenter, observational, 15-year follow-up study involving 136 patients with RRMS, who had initially been treated with either intramuscular (IM) IFNβ-1a or placebo, to identify early predictors of long-term outcomes.

The researchers found that significantly fewer patients treated with IM IFNβ-1a had early disease activity. Of those treated with IFNβ-1a, persistent disease activity was associated with an 8.96-fold higher risk of gadolinium-enhancing lesions, a 4.44-fold higher risk of relapse, and a 2.90-fold higher risk of new T2 lesions. Conversely, early disease activity in placebo-treated patients was not associated with long-term outcomes.

"Disease activity despite treatment with IFNβ is associated with unfavourable long-term outcomes. Particular attention should be paid to gadolinium-enhancing lesions on IFNβ therapy, as their presence strongly correlates with severe disability 15 years later," the authors write. "The results provide rationale for monitoring IFNβ treated patients with magnetic resonance imaging, and for changing therapy in patients with active disease."

This study was supported by Biogen Idec.

Abstract

Objective:
To identify early predictors of long-term outcomes in patients with RRMS treated with IM interferon beta-1a (IM IFNβ-1a).

Methods:
Multi-center, observational, 15-year follow-up study of patients who completed =2 years in the pivotal trial of IM IFNß-1a for RRMS. 136 patients participated in the 15-year follow-up (69 originally randomized to IM IFNβ-1a and 67 to placebo). After the 2-year clinical trial, treatment was not regulated by study protocol. Disease activity during the 2-year trial was defined as: 2 or more gadolinium-enhancing lesions (cumulative) on year 1 and/or year 2 MRI; 3 or more new T2 lesions on year 2 MRI compared to baseline; and 2 or more relapses over two years. Odds ratios were calculated for early disease activity predicting severe EDSS worsening (worst quartile of change, > 4.5 EDSS points) during the 15-year interval.

Results:
The proportion of patients experiencing early disease activity was lower in patients on IM IFNβ-1a than placebo for all disease activity markers (range 23.5%-29.0% vs. 41.0%-45.5%). In the IM IFNβ-1a group, persistent disease activity predicted severe EDSS worsening: gad lesions (OR=8.96, p<0.001); relapses (OR=4.44, p=0.010); and new T2 lesions (OR=2.90, p=0.080). In placebo patients, early disease activity was not as strongly associated with long-term outcomes (OR range=1.53-2.62, p=0.069-0.408).

Interpretation:
Disease activity despite treatment with IFNβ is associated with unfavorable long-term outcomes. Particular attention should be paid to gadolinium-enhancing lesions on IFNβ therapy, as their presence strongly correlates with severe disability 15 years later. The results provide rationale for monitoring IFNβ treated patients with MRI, and for changing therapy in patients with active disease.

Robert A. Bermel MD, Xiaojun You PhD, Pamela Foulds MD, Robert Hyde, Jack H. Simon MD, Elizabeth Fisher PhD, Richard A. Rudick MD

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Source: Doctors Lounge Copyright © 2001-2012 Doctors Lounge (28/09/12)

Biogen Idec announced that two new dosing innovations designed to help patients receiving once-a-week Avonex (interferon beta-1a) for relapsing forms of multiple sclerosis (MS) are now available in U.S. pharmacies:

-- The new Avonex PEN (Avonex 30mcg/0.5mL solution for injection) is the first intramuscular (IM) autoinjector for chronic use, designed to enhance the self-injection process for patients receiving Avonex therapy.

-- A new dose titration regimen, facilitated by the Avostartgrip titration devices, provides patients with the option to gradually increase the dose of Avonex at treatment initiation to reduce the incidence and severity of flu-like symptoms that patients may experience with therapy.

These product enhancements offer the potential for a more tolerable initiation and an easier injection process compared to the Avonex Prefilled Syringe.

"It is our priority to continue to improve our existing treatments like Avonex, which patients have relied on to effectively treat their MS since it was approved in the U.S in 1996," said Douglas E. Williams, Ph.D., Biogen Idec's executive vice president of Research and Development. "Avonex Pen has been shown to help reduce the anxiety patients may experience when self-injecting and for patients initiating treatment, titration can reduce the flu-like symptoms they may have when beginning Avonex therapy."

Avonex Pen is the first IM autoinjector approved in MS treatment. It was designed to enhance the self-injection process and features a substantially smaller needle than the Avonex Prefilled Syringe. The U.S. Food and Drug Administration (FDA) approved the Avonex Pen in February 2012 based on data from a Phase 3b study in which approximately nine out of 10 patients used the device successfully. In this study patients felt significantly less injection pain after they switched from the Prefilled Syringe to Avonex Pen and the patients experienced reduced injection anxiety with Avonex Pen than with the Prefilled Syringe. Ninety-four percent of patients in the study also expressed a preference for Avonex Pen over the Avonex Prefilled Syringe. The top three reasons for this preference were ease of injection, reduction in pain and reduction in injection anxiety.

"One of the key aspects of treating MS is helping patients manage their treatment in order to get the most out of their therapy," said Peter B. Wade, M.D., medical director at the Joyce D. and Andrew J. Mandell Center for Comprehensive Multiple Sclerosis Care and Neuroscience Research at Mount Sinai Rehabilitation Hospital in Hartford, Conn. "For many of my patients, Avonex Pen will help reduce injection-related anxiety and improve the self-injection experience."

The recently-approved Avonex Pen titration schedule can be facilitated by the Avostartgrip kit, a set of three devices that work with the Avonex Prefilled Syringe to administer the appropriate amount of medicine needed to titrate up to a full dose of Avonex over the course of three weeks. The FDA approved this titration regimen in February 2012, based on data from an eight-week, randomized, healthy volunteer study. It showed that a three-week titration period at treatment initiation reduced the severity of flu-like symptoms associated with Avonex treatment by 76 percent, as well as significantly reduced the incidence of flu-like symptoms, versus no titration four to six hours post-injection.

Patients who are new to Avonex treatment have the option to initiate therapy with the Avostartgrip titration kit; once patients have completed the titration regimen, treatment can be continued with Avonex Pen or other approved dosing options.

Avonex Pen is available from the same pharmacies patients currently fill their Avonex Prefilled Syringe prescriptions.

About Avonex Pen

Avonex Pen is the first single-use, once-a-week, fully integrated IM autoinjector for MS. It is designed for use with Avonex treatment in patients with relapsing forms of MS. Avonex Pen integrates the currently approved Avonex Prefilled Syringe and incorporates a smaller needle (25 gauge, 5/8 inch), which is thinner and 50 percent shorter than the standard Avonex Prefilled Syringe needle.

Additional features of Avonex Pen include: a protective injector shield that conceals the needle prior to injection; automated needle insertion and medication delivery; and a diameter and length designed to stabilize Avonex Pen during the injection procedure. In addition, Avonex Pen incorporates a safety lock, which helps prevent injection error and a display window that confirms complete delivery of the medication.

The efficacy and safety of Avonex Pen was evaluated in an open-label, multicenter, Phase 3b study (n=70). Efficacy was assessed through objective and subjective assessments of key aspects of patients' use of Avonex Pen.

About Titration

The Avonex label provides physicians and patients with a clinically-supported schedule for gradually escalating the dose of Avonex at the start of therapy, which has been shown to reduce the incidence and severity of flu-like symptoms that can occur with Avonex treatment. In an eight-week, healthy-volunteer, randomized, Phase 1 study (n=234), a three-week titration period at the initiation of Avonex treatment reduced the incidence (odds ratio:0.18) of flu-like symptoms versus no titration four to six hours post-injection. It also reduced the severity of flu-like symptoms by 76 percent versus no titration four to six hours post-injection.

Titration with Avonex can be facilitated by the Avostartgrip kit, a set of three devices that work with the Avonex Prefilled Syringe to administer three titrated doses of Avonex over a three-week period: 7.5mcg, 15mcg and 22.5mcg. The full dose should be administered at week four.

A titration regimen should only be considered for patients initiating Avonex therapy. Once patients have completed the titration regimen, treatment can be continued with Avonex Pen or other administration options.

Avostartgrip titration kits are provided free of charge to patients who initiate treatment with Avonex.

Source: Market Watch Copyright © 2012 MarketWatch, Inc. (14/05/12)

Biogen Idec said Tuesday that it received U.S. approval for an easier-to-use form of its multiple sclerosis injection Avonex.

The Food and Drug Administration approved the company's Avonex pen, an injection that is designed to reduce pain and anxiety when patients self-administer the drug. The FDA also approved a new dosing schedule for the drug intended to reduce flu-like symptoms often associated with the drug.

Biogen currently offers a program in which registered nurses visit Avonex patients and teach them to self-inject the original form of Avonex. The drug was approved in 1996.

In a separate announcement, Biogen said it submitted an FDA application for an experimental multiple sclerosis pill known as BG-12. The application consists of two company studies showing reduction in disease activity and favourable safety and tolerability, according to the Cambridge, Mass.-based company. Multiple sclerosis is a disease of the immune system in which the body attacks the brain and spinal cord.

Biogen also markets the multiple sclerosis drug Tysabri with Elan Pharmaceuticals Inc.

Source: Canadian Business © 1999-2012 Rogers Communications.(28/02/12)

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