The U.S. Food and Drug Administration (FDA) has approved for
marketing Rebif® (Serono Inc., Geneva Switzerland), a form of
interferon beta-1a, for treatment of relapsing forms of MS. Here
are common questions and answers about this new MS drug.
Q: What is Rebif®?
A: On March 8th, 2002 Serono’s Rebif® (Interferon beta-1a)
was approved by the US Food and Drug Administration (FDA). Rebif®
is a treatment for relapsing forms of MS. It is a form of
Interferon beta-1a, produced by living cells. It is delivered in a
liquid formulation, and must be administered by subcutaneous
injection three times a week. Rebif® is said to reduce the
frequency of relapses and delay the progression of disability.
Q: AVONEX® and Rebif® are similar Interferon beta-1a.
How are they different?
A: The difference is in the delivery. AVONEX® is injected
directly into the muscle. It is believed that IM injection allows
the medication to be released slowly into the bloodstream. Because
effective amounts of AVONEX® stay in the body longer, you don’t
have to inject as frequently. Rebif® is injected under the
skin, not into the muscle. Thus it is thought to remain in the
body for a shorter period, and must be given three times a week.
The two drugs also show markedly different side effects. In a
six-month clinical trial, 92% of patients using Rebif® developed
injection site reactions (redness, pain or swelling), vs only 4%
of patients using AVONEX®. In the 2-year studies of Rebif and
AVONEX, elevated liver function tests, which can indicate
inflammation or damage to the liver, were seen in 27% of patients
using Rebif, vs 8% using AVONEX®. Lowered white blood cell counts
(leukopenia) were seen in 36% of patients using Rebif, vs 1% of
patients using AVONEX®. The most common side effects associated
with AVONEX® treatment are mild, flu-like symptoms—muscle
aches, fever and chills.
Q: Why did the FDA approve Rebif® to be marketed in the
USA? Does it work better than AVONEX® (Interferon beta-1a)?
A: The FDA allowed Rebif to break AVONEX’s market
exclusivity, afforded by the Orphan Drug Act, based on the 24-week
results of an open-label study. The results of any short
term study must be viewed in the context of the fact that MS is a
chronic lifelong disease. The 24-week Serono study
demonstrated a short term advantage for people treated with
Rebif in relapses only (a 12% difference in the proportion of
patients who were free of relapses in 24 weeks). Importantly,
the Serono study does not indicate that Rebif works better than
AVONEX in the long term. In fact, the second 24 weeks of
the same study showed that the risk of relapse was equivalent or,
if anything, slightly less in the people treated with AVONEX
compared to people treated with Rebif. The FDA noted that
Betaseron (approved in 1993) and AVONEX (approved in 1996) for the
treatment of relapsing forms of MS were shown to decrease the
frequency of clinical exacerbations by approximately one-third.
Q: Was Rebif® proven to have a better effect on long-term
accumulation of disability than AVONEX®?
A: No. The 24 weeks study did not support any conclusion
regarding the effects on the accumulation of disability and so
offers only a snapshot of what is happening very early on in the
course of the treatment. The two year phase III study data for
AVONEX® and Rebif® – while not a head to head comparison,
reflect a much more representative period within the lengthy time
course of MS.
In Serono’s Phase III study for Rebif (PRISMS) a 30% effect
on accumulation of disability for the 44 mcg dose was seen over
two years. However, in March 1999, the FDA rejected Serono’s
attempt to enter the US market because its long-term phase III
study of Rebif® did not demonstrate clinical superiority over
Q: Why are some drugs administered just once-a-week and
others more frequently?
A: A drug like AVONEX® is injected once-weekly directly into
muscle tissue (IM), from where it is released slowly into the
bloodstream. Since the drug stays in the body longer, you
don’t have to inject it as frequently. On the other hand,
drugs like Rebif®, Betaseron®, and Copaxone® are injected
subcutaneously, require a frequent dosing, and are thought to
remain in the body for a shorter period of time. Therefore,
these injections must be given more frequently. Most patients on
Rebif® and Betaseron® have to take the injection every other
day, and those on Copaxone® need to take the injection every day.
Ultimately, you must weigh the benefits and the costs jointly
with your physician to choose a therapy that meets your treatment
goals and lifestyle. Once-a-week IM injections are less disruptive
to a patient’s daily schedule than subcutaneous injections given
several times a week. IM injections can also reduce the chance of
having painful and unsightly injection-site reactions—such as
redness, swelling, and tissue death (necrosis)—that can commonly
appear at subcutaneous injection sites.
Q: What long-term factors should I consider before choosing
A: When choosing an MS drug, the most important measure is
whether the drug has a proven ability to slow the accumulation of
disability. MS is a chronic disease: the question is whether the
treatment will maintain its effectiveness and tolerability over
time, or will its benefit eventually wear off?
Staying on therapy is the best way you can positively impact
your MS. Therefore, choose a therapy with side effects you
can manage over the long run. Convenience is another key factor.
Treatments that can be administered easily, quickly and less
frequently may be easiest to live with.
AVONEX® (Interferon beta-1a) is indicated for
the treatment of relapsing forms of multiple sclerosis to slow the
accumulation of physical disability and decrease the frequency of clinical
The most common side effects associated with
AVONEX® treatment are flu-like symptoms, muscle ache, fever, and chills.
Other common side effects seen, but not statistically different from
placebo, were headache (AVONEX®: 67%, placebo: 57%), pain (AVONEX®: 24%,
placebo: 20%), and asthenia (weakness) (AVONEX®: 21%, placebo: 13%).
AVONEX® should be used with caution in people
with depression and in people with seizure disorders. AVONEX® should not
be used by pregnant women. People with cardiac disease should be closely
monitored. Routine periodic blood chemistry and hematology tests are
recommended during treatment with AVONEX®.
Please see FULL PRESCRIBING INFORMATION for
AVONEX® (Interferon beta-1a).