Revlimid (lenalidomide)

Revlimid (lenalidomide)

FDA Approves New Treatment for Myelodysplastic Syndrome (MDS)

The Food and Drug Administration (FDA) has approved the drug Revlimid
(lenalidomide) for the treatment of patients with a subtype of
Myelodysplastic Syndrome (MDS). The subtype is MDS patients with
deletion 5q cytogenetic abnormality.

MDS is a collection of disorders in which the bone marrow does not
function normally and the body does not make enough normal blood cells.
Patients with MDS may need blood and platelet transfusions and
antibiotic therapy for infections. In clinical trials, patients treated with
Revlimid no longer needed transfusions, with most patients becoming
independent of transfusion by three months. The transfusion-free period
lasted for an average of 44 weeks.

"This new product will offer a much needed treatment option for patients
suffering from this rare illness that, in some cases, has been found to
progress to fatal forms of leukemia," said Dr. Steven Galson, M.D.,
Director of FDA's Center for Drug Evaluation and Research (CDER).

MDS can develop following treatment with drugs or radiation therapy for
other diseases, or it can develop without any known cause. Some forms
of MDS can progress to acute myeloid leukemia (AML), a type of cancer in
which too many white blood cells are made.

An estimated 7,000 to12,000 new cases of MDS are diagnosed yearly in
the United States. Although MDS occurs in all age groups, the highest
prevalence is in people over 60 years of age. Typical symptoms include
weakness, fatigue, infections, easy bruising, bleeding, and fever

Revlimid is structurally similarto thalidomide, a drug known to cause
severe birth defects. Additional studies are ongoing in animals to address
whether there is a risk that Revlimid will also cause birth defects when
taken during pregnancy. While these studies are under way, the
company is marketing Revlimid under a risk management plan called
RevAssist, designed to prevent fetal exposure.

Under RevAssist, only pharmacists and prescribers registered with the
program will prescribe and dispense Revlimid. The program requires
patients, including female patients undergoing mandatory pregnancy
testing, to give informed consent before starting Revlimid. Physicians are
to check pregnancy tests, limit prescriptions to a one-month mail supply,
and report any pregnancies to FDA. FDA and the manufacturer will re-
evaluate the risk management plan when results of further animal testing
for birth defects are completed.

The labeling for Revlimid will include a Black Box Warning and a Medication
Guide regarding the prevention of fetal exposure. Additional Black Box
Warnings include the potential need to lower the dose due to
suppressed blood counts and increased risk of blood clots. Common side
effects reported with Revlimid include thrombocytopenia (low platelet
count), neutropenia (low white blood cell count), diarrhea, pruritis (itch),
rash, and fatigue.

Revlimid is distributed by Celgene Corporation of Summit, N.J.

FDA News FDA Approves New Treatment for Myelodysplastic Syndrome
(MDS) December 28, 2005

Questions and Answers on Revlimid (lenalidomide)

1.

What is Revlimid used for?FDA Approves New Treatment for
Myelodysplastic Syndrome (MDS)

     Revlimid (lenalidomide) is approved to treat a subgroup of patients
with Myelodysplastic Syndrome (MDS).

2.

What is MDS?

     MDS is a collection of disorders in which the bone marrow does not
function normally and not enough normal blood cells are made. MDS may
develop following treatment with drugs or radiation therapy for other
diseases or it may develop without any known cause. Some forms of MDS
can progress to acute myeloid leukemia (AML), a type of cancer in which
too many white blood cells are made.

3.

Is there a Risk Management Plan in place for Revlimid?

     Yes. The sponsor, Celgene Corporation, submitted a Risk
Management Program to prevent pregnancy exposures to this drug. This
program is called RevAssist.

4.

Why is there a Risk Management Plan for Revlimid?

     Because of the potential for birth defects, exposure of a developing
fetus to this product must be avoided. Revlimid will only be available
under a special restricted distribution program approved by FDA.

5.

What are the goals for RevAssist?

     The goals of the RevAssist plan are to:

     *

       Prevent fetal exposure to Revlimid by registering and educating all
physicians, pharmacists and patients and monitoring pregnancy
prevention activities.
     *

       Reduce the risk of fetal exposure from males taking Revlimid who
engage in sexual contact with a female partner of child bearing potential.
     *

       Educate physicians, other healthcare providers, and patients about
potential lowering in blood cell counts (cytopenias) associated with
Revlimid therapy.

6.

Will the labeling for Revlimid have a Black Box Warning or Medication
Guide?

     In addition to the RevAssist program, the labeling for Revlimid will
include a Black Box Warning discussing the possibility of birth defects,
increased risk of lowering of blood cells or platelets, and increased risk of
blood clots. A medication guide is also part of the approved labeling, and
must be given to patients with each prescription.

7.

Is this product the same as thalidomide?

     This product is chemically similar to thalidomide, but is not the same
as thalidomide.

8.

Is this Risk Management Program the same as the program in place for
thalidomide?

     The RevAssist program has very similar components to the program
for thalidomide (System for Thalidomide Education and Prescribing Safety
(S.T.E.P.S.) but does differ in some areas.

9.

What are the key similarities to the thalidomide S.T.E.P.S. program?

     Both programs include the following safety measures:

     *

       Mandatory registration of all patients, prescribers, and pharmacies
     *

       Pregnancy testing in all females of childbearing potential
     *

       Education for prescribers, pharmacists, and patients
     *

       No refills and a 28-day limit to prescriptions

10.

What are the key differences to the thalidomide S.T.E.P.S. program?

     The main differences between the two programs are in the following
areas:

     *

       Distribution -- Revlimid will be distributed to specialty pharmacies;
while thalidomide is distributed to both retail and specialty pharmacies
registered in the S.T.E.P.S. program.
     *

       Pharmacist interaction Â– Pharmacists will call patients on the
telephone to educate them about the potential for birth defects before
dispensing Revlimid. With thalidomide, patients get face to face
counseling from their pharmacists.
     *

       Education materials Â– Revlimid educational materials include a
medication guide and other patient brochures. Materials for thalidomide
include an educational video in addition to a brochure.
     *

       Packaging Â–Thalidomide comes in blister packs with additional
safety information. Revlimid does not have blister packaging.

11.

Does this product cause the same type of birth defects as thalidomide?

     The company performed two studies in animals to look for evidence of
birth defects. After review of these studies, FDA believed they were
inadequate to accurately characterize the risk of birth defects with fetal
exposure to the active ingredient in Revlimid, lenalidomide, and has
recommended additional studies in order to more fully assess whether or
not this product may cause birth defects in pregnant females that are
similar to those caused by thalidomide.

12.

What must a female patient of child bearing potential do to obtain a
prescription for Revlimid under the RevAssist program?

     Before obtaining a prescription for Revlimid, females of child bearing
potential must be counseled by a physician or an expert in contraception
not to get pregnant while taking Revlimid. If necessary, females of child
bearing potential will be taught why and how to use 2 effective methods
of contraception at the same time in order to avoid pregnancy. All females
of child bearing potential must pass a test at the start of treatment and
each subsequent month of treatment to make sure they understand
pregnancy prevention and that their risk of fetal exposure is low. The test
is done by using push buttons to answer questions asked over the
telephone.

     Also before starting Revlimid, females of child bearing potential must
sign (along with the physician) an agreement to show they understand
the need not to get pregnant while taking Revlimid. females of child
bearing potential must have 2 negative pregnancy tests documented by
their doctor to start Revlimid. The first test should be performed within 10-
14 days, and the second test within 24 hours prior to prescribing
Revlimid. A negative pregnancy test, along with a satisfactory the phone
test, is needed from female of child bearing potential every month before
a new Revlimid prescription can be dispensed.

13.

What will FDA do if exposure to this product results in birth defects?

     Any suspected fetal exposure to Revlimid should be reported to the
manufacturer or to FDA via the MedWatch system. Celgene will follow all
exposed pregnancies to see if any birth defects occur. If birth defects are
seen or if fetal exposures to Revlimid are reported, FDA will re-evaluate
the program to see if it should be modified since these should not occur if
the RevAssist program is working like it is supposed to.

14.

How will the use of Revlimid be monitored?

     As with all drugs, FDA will carefully monitor the use of this product
once it is on the market. In addition, Celgene plans to evaluate
pregnancy and other adverse events through the following measures:

         *

           Reports on pregnancy Â– The company plans to measure the
number of exposed pregnancies and outcomes via spontaneous adverse
event reports. They will rapidly notify FDA about all exposed pregnancies
and outcomes under expedited reporting mechanisms.
         *

           Audits of the specialty pharmacies to determine whether there is
consistency and adherence to the RevAssist program.

15.

How will Revlimid be supplied?

     Revlimid will be available as 5 mg or 10 mg oral capsules. Revlimid will
be limited to a maximum of a 28 day supply.

16.

Will Revlimid be prescription only or available over-the-counter?

   Revlimid will be available by prescription only from physicians and can
be filled only by a limited number of specialty pharmacies. Most of these
pharmacies will operate by fax, phone calls, and express shipments to
patients.

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