Epogen
Todd Harris
1. Safety
2. Efficacy
1. Kidney
2. Genetically engineered
1. Improvements
2. Anemia
1. High dosage
2. Death
Company
Epogen is produced by the company Amgen. Amgen located atThousand Oaks,
California, is a global biotechnology company. It discovers, develops, manufactures,
and markets human therapeutics based on advanced cellular and molecular
biology. Amgen, founded in 1980, is now the largest biotechnology company
in the world. It has 4,200 employers around the world and 2,700 of the 4,200
workers, work at the headquarters in Thousand Oaks. Amgen has centers of
research in "Boulder, Colorado and Toronto, Canada; clinical research
centers in Cambridge, England and Melbourne, Australia; the international
distribution center in Louisville, Kentucky, fill and finish facility in
Junco, Puerto Rico; and European regional headquarters in Lucerne, Switzerland.
Amgen has other international offices that are located in Austria, Australin,
Belgium, Canada, China, France, Germany, Italy, Japan, the Netherlands,
Hong Kong, Portugal, Spain, and the United Kingdom." (Amgen 1996)
Amgen's first product, Epogen was approved in June 1989 for use in the United
States. Neupogen (filgrastim) Amgen's second product, received approval
for use in February 1991, is used for preventing infections in cancer patients
that receive chemotherapy for bone marrow and peripheral blood progenitor
cell transplantation patients and treatment for chronic neutropenia, which
is a rare blood disorder. Amgen has research in the areas of hematopoiesis,
neurobiology, inflammation/autoimmunity, and soft tissue repair and regeneration.
Products from the research, in the four areas mentioned from above, may,
sometime in the future, be used in treating conditions characterized by
disorders of blood and bone marrow, neurodegenerative diseases such as ALS,
Parkinson's, Alzheimer's, or traumatic nerve injury.
Epogen
Epoetin Alfa recombinant Epogen, or Epogen, has 3,000 units of recombinant
Epoetin Alfa, 2.5 mg Albumin (Human) in sterile buffered solution (pH 6.9
+/- 0.3) of sodium citrate (5.8mg), sodium chloride (5.8mg), citric acid
(0.06mg), in Water for injection.
Its uses are stimulating the body to make red blood cells, treatments of
anemia (loss or reduction of red blood cells) associated with chronic renal
failure or anemia caused by AZT (zidovudine) in HIV-infected persons. Before
Epogen was produced or used, blood transfusions and male hormone therapy
was used in treating anemia, which was caused by chronic renal failure.
Epogen Studies
Studies on Epogen are available from Amgen, Food and Drug Administration
(FDA), and the Journal of the American Society of Nephrology. One study
by Amgen was "to establish the safety and efficacy of EPOGEN in pediatric
patients" (Amgen 89), the second study from FDA, was about erythropoietin,
which is a protein produced by the kidney and is genetically engineered
by scientists, the third study from the Journal of the American Society
of Nephrology, was about improvements in the quality of life for kidney
dialysis patients, and the last study, also by Amgen, was about how Epogen
in dialysis patients who have severe heart disease was receiving high doses
of Epogen, which ended up killing the patients instead of helping them,
but this is ONLY the patients who are on dialysis with severe heart diseases.
The other patients without severe heart diseases are according to the reports
okay and have not died because of Epogen.
This study by Amgen was to make sure that Epogen is safe and beneficial
for children (pediatric patients). Before the study was initiated, the company
(Amgen) had done clinical trials in about 15 children. Once Amgen had received
the test results showing that the clinical trials was safe and beneficial,
the company then began a nationwide study consisting of about 200 pediatric
patients, who have end-stage renal disease and need hemodialysis (the machine),
or peritoneal dialysis, which is in a plastic bag.
The dialysis machine takes out the blood from the body and cleans it. The
machine does this by diffusing waste products through the tubing that contains
a permeable membrane, by a fluid called dialysate. The concentration gradient
between the blood and fluid (dialysate) has to be maintained and in order
to do that the dialysate has to be continuously replaced. This technique
is done three times a week for several hours, this could damage blood cells,
and anticoagulants must be added, to avoid possibilities of bleeding problems.
On the other hand, Continuous Ambulatory Peritoneal Dialysis (CAPD), does
not take as long as the machine, it also does not cause possible damage
to the blood cells, but because the catheter has to stay inside the body,
there is a high risk for infection. The reason CAPD does not take long to
do is because the catheter is inside the peritoneal cavity which has a selectively
permeable membrane (peritoneum), this allows substances to move back and
forth across the membrane very quickly. CAPD like the machine uses dialysate,
but instead of a machine pulling blood out and pumping blood back into the
body, the dialysate is put directly into the peritoneal cavity, from a plastic
bag (hanging above the abdomen) by mere gravity and then when the patient
is ready to discard the waste products (dialysate has been dwelling in the
body for at least two hours or more), the patient then puts the plastic
bag below the abdomen and opens the roller clamp ( device that pinches off
tubing so fluid will not flow out or to allow fluid to flow out at proper
time) to allow waste and used dialysate back out and then he/she is ready
to put in new dialysate and start the whole process again. This process
can be done almost anywhere ( as long as it is clean and sterile) and depending
upon the results of the patient's blood tests, weight, and blood pressure
the amount of times the process is done during the day varies.
Amgen's study procedures had two parts to it. The first part is randomized
and the second part is nonrandomized. The first 12 weeks the patient has
a chance of getting Epogen or a placebo ( salt and protein solution, but
no Epogen in it). The placebo is neither helpful nor harmful to the patient.
During this time, the doctor, the nurse, the patient's parents, and the
patient do not know which the patient is receiving, the placebo or Epogen,
and Amgen used code numbers for the patient's ID, so the company could not
be able to really tell who was getting the placebo or Epogen, anyway. If
the patient had the placebo for the first 12 weeks, then he/she would get
Epogen for 36 weeks and if he/she was on Epogen for the first 12 weeks,
then he/she would get Epogen for 24 weeks. Also, if the red blood cell count
gets high too quickly or above the desired level the doctor should then
reduce the dose. In the second part of the study everybody knows that the
patient is getting the Epogen. The patient will receive Epogen 3 times a
week, (Epogen at this time was a single dose in a vile) but can be changed
to less or more times during the week in order to obtain the right level.
For patients living too far away, family members can be trained to give
shots 3 times a week. The shots are rotated right to left in the upper part
of the arms and from right to left in the upper part of the legs. Some patients
take the shot in the stomach (ouch!). The amount of iron in the blood has
to be monitored (in case patient needs more iron, iron pills are prescribed)
as well as the blood pressure has to be monitored. Numerous sheets of logs
need to be computed to monitor drug administration, and blood pressure,
when the log sheets were used up they are sent back to the company Amgen.
The study runs tests such as physical examinations every 6 months, chest
x-rays, blood samples, culture taken from peritoneal fluid of peritoneal
dialysis patient before entering the study, throughout the study patient's
diet is nutritionally analyzed by what the patient consumes and how much
is consumed, height and weight, head circumference of patients that are
36 months of age or less, tests that determine bone's age and hormone levels,
and sexual development taken throughout the study. The testing is for determining
the "quality of life" (Amgen 89) and learning ability. Each month
blood was drawn to check the red blood cell count, and every so often tests
were computed on mental and emotional well being. There were drawing tests
to check long term memory, there was a vocabulary test, there were questions
to answer about emotional as well as physical state, there was a math test,
there were tests for mental reflexes, and also tests for short term memory.
The second study is in the clinical series on erythropoietin was for AIDS
patients who are anemic or at the early stages of infection with AIDS virus
experience while taking AZT (zudovudine). Through " treatment IND (Investigational
New Drug)" (FDA 1991) protocol in June of 1989, the FDA (Food and Drug
Administration) permitted erythropoietin, while being investigated for AIDS
indication made widely available to patients on AZT. The study involved
297 AIDS patients, who experienced severe anemia from zudovudine (AZT).
From the 297 AIDS patients, 118 of them were involved in a placebo-controlled
trial, in which patients who had low Epo (erythropoietin) levels resulted
in 40% reduction in blood transfusions for Epoetin-treated patients during
the three month period. The conclusion to the study was patients with relatively
low levels of naturally occurring erythropoietin may benefit from the treatment.
Amgen manufactured and did most of the work in developing erythropoientin.
The product will be marketed under agreement with Ortho Pharmaceutical Corp.
(location: Raritan, N.Y.) who sponsored the clinical trials and treatments
for IND (Investigational New Drug) for erythropoietin in AIDS patients.
Amgen will be marketing Epoetin Alfa as Epogen and Ortho will be marketing
it under the name of Procrit.
The third study was published in the Journal of the Amgen Societyof Nephrology.
The study showed genetically engineered protein Epogen(Epoetin Alfa) provides
substantial impact on the quality of life in kidney dialysis patients. In
the study, patients who receive the epogen treatments attained "significant
improvements in vitality, physical functioning, social functioning, mental
health, looking after the home, social life, hobbies, and satisfaction with
sexual activity." (Journal of the American Society of Nephrology) Many
patients receiving dialysis were severely handicapped by the debilitating
anemia, found in about 90% of dialysis patients. The study, National Cooperative
Recombinant Human Erythropoietin Study, dialysis patients were given standard
tests which gaged the many dimensions of functional health and well-being.
The results were then measured against the results in groups of patients
who had other diseases that had received the same standard tests.
Dialysis patients who not yet received Epogen usually had lower baseline
scores than patients with congestive heart failure or chronic depression.
After about 99 days of Epogen treatments, their quality of life scores were
significantly higher than those who had the other disorders. Vitality was
the most affected by the treatment.
The fourth study, was about higher doses of Epogen given to dialysis patients
who had severe heart disease, such as congestive heart failure and heart
attack. Doctors thought that boosting the red blood cell count of the patients
by using more of the Epogen would improve the patient's heart condition,
but instead it made their death rates increase. 631 patients out of more
than 1,200 dialysis patients with severe heart disease, received Epogen
in a dosage that maintained their red blood cell counts at a level commonly
accepted during treatment. Of those 631 patients 181 or 28.6% died. In a
group 634 patients whose red blood cell counts were boosted by Epogen to
a higher level commonly found in people without kidney disease, 221 or 34.8%
died. The doctors then heading the study decided Saturday 22, 1996 to end
it, after a panel of outside investigators alerted Amgen to the patients
deaths two weeks ago. "Dr. Allen Nissenson, professor of medicine at
the University of California at Los Angeles and principal investigator of
the study said": 'Nothing in these study results suggests that any
changes should be made in the treatment of dialysis patients who are receiving
the currently approved treatment.'(Amgen 1996)
Benefits
The benefits and side-effects of Epogen are many. Amgen's statement on benefits
follows:
No benefit is guaranteed from participating in this study (
Amgen's nationwide study Epogen being tested on pediatric patients). However,
Epogen may increase your child's hematocrit ( red blood cell count) and
eliminate the need for blood transfusions. Blood transfusions carry the
risk of infections and the risk of eliminating certain kidneys for possible
transplantation because of the danger of rejection reactions to the kidney.
Treatmentwith Epogen has been shown effective in correcting anemia in adults.
(Amgen 89)
Also, now the Epogen comes in multidose in a vial, where in the study it
was just a single dose in a vial. The advantage to this is that a patient
doesn't have to get a vial each month, this avoids having to pay more money
out for Epogen. Although shots are a discomfort, the reduction in transfusions
is a big advantage.
Side-effects
The potential risks or side-effects are some adults have aches and pains
after infusion (of Epogen). If the drug is given under the skin, it may
sting or burn, now the medicine has a saline solution added to it, where
as before patients had to mix the saline with the Epogen if the Epogen stung.The
side-effects a patient may have are high blood pressure, clotting in the
device that's used to connect the patient to the dialysis machine, headache,
nausea, vomiting, muscle aches, diarrhea, high potassium, a cough may occur,
and rare instances of seizures. If the side-effects develop into rapid heartbeat,
shortness of breath, hives, itching, or skin rash, tell the doctor right
away. Amgen did not see any other side-effects in the 15 pediatric patients
from the study. If the patient is pregnant before the study she is not allowed
to participate, and if she is pregnant during the study, Epogen is stopped,
because of the unknown risks to the embryo. Also, if she decides to become
sexually active during the study she must agree to use birth control that
the doctor "considers effective and medically acceptable" (Amgen
89), and that the patient "accept the risk that pregnancy could result."
(Amgen 89)
Ethics
Shelly White, a nurse a Nephrology Incorporated indicates that Epogen is
available to both peritoneal dialysis and hemodialysis patients. Patients
on hemodialysis receive the shot while they are receiving dialysis treatment
from the machine. A person's insurance will pay for Epogen, but that Medicare
eventually, pays for it. Lisa Woodcox of the billing department at Nephrology
Incoporated says that the amount of Epogen in the vial given to the patient
determines the cost. For example, one vial of 40,000 units costs $250. The
cost may also depend upon how much the insurance company will pay. Sometimes
insurance will pay 100 percent, but usually most insurances will pay 80
percent.
Amgen says that Epogen was out on the market starting in 1989 all the way
up to the present and is still on the market, which means it has been on
the market for 7 years now. Also Procrit, which is still Epoetin Alpha just
a different name for Epogen, was on the market starting on January of 1991
also up to the present and is still on the market for 5 years now. The Ortho
Biotech customer service indicates that Epogen is available to people whose
doctor prescribes it to them. Basically through the doctor's prescription
to people, that the doctor believes needs it. Also, Epogen is available
to dialysis patients in other countries as Erythropoietin Human Recombinant
Epoetin Alpha.
Conclusion
From an ethical point of view I would say that the Amgen company did test
and research Epogen thoroughly for adults as well as children. The advantage
point of Epogen is that it reduces the amount of blood transfusions, reduces
the rejection reaction of possible kidney transplants, and reduces the risk
of infection. The disadvantage point of Epogen is it is given through injection,
which gives a small chance for infection, medicine stings, possiblity of
headache, nausea, vomitting, high blood pressure, high potassium, a cough,
rapid heartbeat, shortness of breath, itching, hives, or skin rash. Also,
if patient is pregnant, there are unkown risks to the embryo. Although there
seems to be more side-effects than benefits, the benefits outweigh the side-effects,
Epogen studies done by Amgen proves, and therefore is considered safe.
Bibliography
Amgen Incorporated, "A Phase III Double-Blinded, Placebo-Controlled
Study of Epogen (Epoetin alfa) in Pediatric Dialysis Patients (Protocol
# EPO-9002) ."
IUPUI INFORMED CONSENT STATEMENT rev. November 1989: pages 1-7.
Amgen Incorporated, "Amgen Inc." Synergistic Designs, Inc., 1996.:
Pages 1-2.
World Wide Web http: // www.biospace.com/g/synd/ _c0...hib_script/exhibitors/
AMGENInc.html 10/13/96 14:40:27
"Anemia drug trial suspended as some patients' death rates rise."
Nando.net The Associated Press,
1996: Pages 1-2. WorldWideWeb
http://www.nando.net/newsroom/ntn/health/062596/health2_2140.html 10/13/96
14:56:17
Food and Drug Administration. "Epo for AIDs Related Condition."
News 01/02/1991:
Pages 1-2. World Wide Web http://www.hivpositive. com/f-DrugAdvisories/11-FDA/
7.html 10/12/96 13:35:19
Friedlander, Ed, "Kidney." January 1996: Pages 1-68.
Worldmall http//worldmall.com/erf/lectures/kidney.txt 10/12/96 14:07:01
"Medication Information Sheet (The Cheshire Medical Center) EPOETIN
ALFA - INJECTION (Epogen)." Jeffrey P. Newcomer : Pages 1-2.
World Wide Web 10/12/96
"Study Shows Improved." Journal of the American Society of Nephrology:
Pages 1-2. World Wide Web http://www.napsnet.com/health/34400.
html 10/13/96/ 14:50:08
White, Shelly. Personal Interview. November 13, 1996.
Woodcox, Lisa. Personal Interview. November 13, 1996.
Ortho Biotech. Personal Interview. November 13, 1996.
Appendix. . . . Personal Experience
Anytime I am allowed to do a report on a topic of my own choice, I usually
do it on medicine that I take or have taken, or on one of my
medical problems. I choose this sort of topic in order to learn more about
it and also to inform others about me. This is why I chose Epogen. I take
Epogen for anemia, and the reason I am anemic is because I have no kidneys,
which make erythropoietin, a protein that stimulates the production of red
blood cells. I have no kidneys because my two original kidneys never grew
after birth (hypoplastic kidneys). From 8 years old to about 16 years old,
I had two kidney transplants. The first transplant lasted for 8 years and
the second transplant lasted for 8 months. The explanation for why they
didn't last for ever is because my body attacked them and beat them up as
if it were fighting infections and so after awhile the kidneys wore out.
Also, transplanted organs never last for ever. Now I am on a form of dialysis
called continuous ambulatory peritoneal dialysis (CAPD) with no kidneys,
which surprises most people, but I have heard of people, who are on dialysis
and still have their kidneys, this is because they have a kidney disease
and not the same problem that I had.
I started dialysis in April of 1991 when I was 16 years old. A couple of
months later, my doctor, Dr. Jerry Bergstein told us about a drug called
Epogen and its company Amgen. He told us that Epogen was used in adults,
but in order for children to take it, they have to be in a study and monitored
very closely. Dr. Bergstein wanted me to be on Epogen and thought that I
would benefit from it, so we (my mother and I) decided that I would go ahead
and be on Epogen. This meant I had to agree to go on the study, but if for
any reason I decided to withdraw from the study, I could do so without any
penalties. Also, if the doctor decides that it is best for the patient to
stop using Epogen or the study is stopped by Amgen, here again there are
no penalties. From the research information and from my own personal experience,
I feel that Epogen is an ethical drug to use, as well as a drug that was
approved safe by the FDA because of the fact that its benefits outweigh
the side- effects.