Effectiveness

The Importance of Effective Treatment

With relapsing MS, it's important to start treatment soon after diagnosis and to use an effective product that you can take consistently over time. Even during the periods when the disease appears "quiet," MS may still be having an effect on your central nervous system.

Rebif: supported by clinical data

Overview

In the PRISMS* study, the efficacy and safety profile of Rebif^® (interferon beta-1a) was established over 2 years. Over those 2 years, Rebif was shown to reduce the activity and area of brain lesions on MRI, reduce the frequency of relapses, and delay disability progression. Rebif is the only therapy for relapsing MS that has been proven to work better when compared with another therapy in a class I head-to-head trial. Rebif 44 mcg given 3 times a week has also been proven to work better than Avonex 30 mcg given once a week at reducing brain lesion activity on MRI and preventing relapses at 48 weeks. This was proven in the EVIDENCE** study where Rebif 44 mcg given 3 times a week was proven to work better than Avonex 30 mcg given once a week at reducing brain lesion activity on MRI and preventing relapses at 48 weeks.

The exact correlation between MRI findings and the current or future clinical status of patients, including disability progression, is unknown.

The PRISMS study

The PRISMS study was one of the largest placebo-controlled studies of an interferon therapy ever conducted in relapsing-remitting MS. It included 560 people with relapsing remitting MS.

The PRISMS study demonstrated the effectiveness of Rebif in relapsing forms of MS. For over 2 years, people in the study were given Rebif 22 mcg, Rebif 44 mcg, or placebo. Over 2 years, Rebif demonstrated significant benefits for reducing lesion activity and area, preventing relapses, and delaying disability progression.

Rebif is proven effective in all 3 of the following key areas

• Delaying disability progression
• Preventing relapses
• Reducing MRI lesion activity and area

Rebif: PRISMS 2-year data

• Rebif is proven to significantly slow the progression of MS: 74% of people taking Rebif 44 mcg had no disease progression at 2 years vs 63% of patients taking placebo
• Significantly more people were relapse free at 2 years with Rebif 44mcg vs placebo (32% vs 15%)
• Rebif 44 mcg more than doubled the time to relapse. This means people taking Rebif had more than twice as much time before a relapse compared with people taking placebo
• Rebif has been shown to reduce the need for steroid treatment for MS
• Rebif reduced the number of new MRI brain lesions by an average of 78% compared with placebo
• MRI brain lesions had decreased in size in people taking Rebif. In comparison, MRI brain lesions grew larger in people taking placebo.

The exact correlation between MRI findings and the current or future clinical status of patients, including disability progression, is unknown.

PRISMS safety information.

In the PRISMS 2-year study, only about 5% of people left the study because of side effects with Rebif. The most common side effects with Rebif were usually mild or moderate. They included injection-site reactions, which were rarely a cause to stop therapy, and flu-like symptoms (fever, chills, muscle aches, tiredness). Side effects tend to diminish over time.

Other common side effects with Rebif are depression, abdominal pain, increased liver enzymes, and blood cell count decreases.

Patients who returned for a follow up visit after up to 8 years of treatment with Rebif reported no new types of serious safety issues.

The EVIDENCE study

Rebif is the only therapy for relapsing MS that has been proven to work better than another therapy in a class I† head-to-head trial. The 24-week results from the EVIDENCE study helped lead to the 2002 FDA approval of Rebif.

To date, the EVIDENCE study is the only completed, head-to-head, class I study that compares the efficacy of 2 interferon-beta therapies in relapsing MS. In this study, 339 people were treated with Rebif and 338 people were treated with Avonex.

Those treated with Rebif injected 44 mcg 3 times a week. Rebif was injected just under the skin. The Avonex group injected 30 mcg once a week into the muscle.

At 48 weeks, Rebif was proven to work better compared with Avonex at:

• Reducing MRI lesion activity
• Preventing relapses

58% of people taking Rebif had no new brain lesions on MRI, compared with only 38% of people taking Avonex

The exact correlation between MRI findings and the current or future clinical status of patients, including disability progression, is unknown.

EVIDENCE Safety Information

Side effects are generally similar between Rebif and Avonex.

Side effects that were more frequent with Rebif include mild skin reactions, and liver enzyme and blood cell count changes. Flu-like symptoms were more frequently observed with Avonex than with Rebif.

The study also showed that:

• Patients taking Rebif 44 mcg had fewer MS-related hospitalizations and steroid treatments than patients taking Avonex 30 mcg
• Fewer people treated with Rebif had flu-like symptoms than people treated with Avonex

The benefits of changing therapy to Rebif

At the end of the EVIDENCE** study, people taking Avonex were given the option of leaving the trial or changing to Rebif therapy. Seventy-three percent of people taking Avonex chose to change therapy to Rebif. Compared with their last 6 months on Avonex, after changing to Rebif 44 mcg therapy for an average of 8 months, they had:

The exact correlation between MRI findings and the current or future clinical status of patients, including disability progression, is unknown.

Rebif has a well-established safety profile

The safety of Rebif has been evaluated in a 2-year placebo-controlled trial (PRISMS*) and in a 48-week trial vs Avonex (EVIDENCE**). Patients from PRISMS who returned for a follow up visit after up to 8 years of treatment with Rebif reported no new types of serious safety issues. Along with this clinical trial experience, Rebif has over 12 years of worldwide patient experience. So you can feel confident that the safety profile of Rebif is supported by long-term information.

Rebif – the drug that made history

Rebif was approved by the FDA in 2002 because it met the requirements of the Orphan Drug Act for superior efficacy.

The Orphan Drug Act gives a 7-year market exclusivity to a company that develops a treatment for a rare disease, such as MS. In 1996, Avonex was granted 7-year market exclusivity for MS in the United States under the terms of the Orphan Drug Act. Exclusivity was granted through May 2003. Because the makers of Rebif wanted FDA approval before then to give people living with relapsing MS more treatment options, they had to show Rebif was either safer or worked better than Avonex to overcome the exclusivity. In a head-to-head study, Rebif 44 mcg tiw proved to work better than Avonex 30 mcg qw at reducing the frequency of relapses. This was proven at 24 and 48 weeks. This effect was maintained through an average of 64 weeks.

The FDA granted Rebif the FIRST exception to the exclusivity rule based on efficacy.

Compared to Avonex, side effects were generally similar despite the higher, more frequent dosing of Rebif 44 mcg tiw with three exceptions. As to be expected with higher, more frequent dosing, people taking Rebif had a greater number of injection-site reactions (85% Rebif vs. 33% Avonex), liver disorders (18% Rebif vs. 10% Avonex), and white blood cell disorders (13.6% Rebif vs. 5.3% Avonex). However, the rates of discontinuation or serious adverse events were similar for the two drugs. Flu-like symptoms were significantly higher for people taking Avonex than for people taking Rebif (45% Rebif vs. 53% Avonex).

Avonex is a registered trademark of Biogen Idec.