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HEALTH
ddC: Problems & Promises
Studies suggest excellent results from the drug when used alone and in conjunction with AZT, but activists are calling
for a boycott of Hoffmann-La Roche products because of delays in making ddC available.
by Kathleen Brockel, Atlanta NAPWA Treatment Advisory Committee
“I had to build special shelving in my
office to hold the four inch thick binders,”
said Atlanta Infectious Disease physician
Dr. Steve Marlowe, referring to the stack
of paperwork requiredto enroll and moni
tor patients in the Hoffmann-La Roche
ddC expanded access program.
Atlanta physician Rick Hudson
enrolled the first patient in the country
into the Roche's ddC expanded access
program. It took him twelve hours to com
plete the paperwork process. Then he was
told by Roche that it would be 3 to 4
months before his patient would receive
the drug.
ddC is a nucleoside analogue (as are
ddl and AZT) which has antiretroviral
activity against HIV. ddC's efficacy has
been suggested by increased CD4 counts,
weight gain and reduction in p24 antigen
levels. Reported side effects are generally
attributed to higher doses (.06 & .03
mg/kg of body weight) of ddC used in
phase I trials. Those side effects can
include peripheral neuropathy (tingling,
numbness or pain in the hands and feet,
neutropenia-a type of low white blood cell
count), thrombocytomenia (low platelets)
and rash. The toxicities are nonexistent,
or much less severe, in lower doses of
ddC (.01 or .005 mg/kg of body weight).
Current recommendations call for one or
two ,375mg tablets taken orally three
times per day.
A person with HIV is eligible to get
ddC through expanded access if he or she
has experienced AZT treatment failure,
AZT intolerance, or is ineligible for AZT.
These are specific definitions set by
Roche which outline criteria for lab val
ues, symptoms, and time frame for eligi
bility. (A summary list is printed in issue
#113 of John James Treatment News
available in the NAPWA office.)
Expanded access programs are meant
to allow access to potentially life enhanc
ing and life saving drugs for people who
are ineligible for standard, FDA approved
drugs while those drugs are still in clinical
trials. But, for a variety of reasons, peo
ple are often not eligible to participate in
expanded access programs. They may be
taking other medications which might
skew the results of a drug trial. Additional
safety data on the drug is collected
through the program, whereas efficacy
data is collected through standard drug tri
als.
And drug companies are not allowed
to charge for the drag through expanded
access.
“Patients die while doctors fill out
forms” is the tag line coined by ACT UP
New York’s “Boycott Roche” campaign.
Boycott organizers charge that people
with HIV are waiting as long as four to
seven months to receive ddC through the
expanded access program. They say that
problems stem from Hoffmann-La
Roche’s refusal to ask the government for
a “national” IRB approval—experimental
drag protocols must be approved by insti
tutional review boards. Because there is
no national IRB for ddC, physicians
whose patients want to use the drag must
get approval from local IRB's—through
hospitals or research institutions. A sec
ond obstacle is the paperwork required for
each patient enrolled, a stack thicker than
an Atlanta telephone directory.
ACT UP calls for a boycott against
Roche services and products (Valium,
Librium, Dalmane and Roferon A) until
demands are met to: replace local IRB
approval with a national IRB; reduce
monitoring paperwork from 6 pages every
2 weeks to 2 pages every 4 weeks; deliv
ery of the drag in less than 3 weeks; and
formal toxicity reporting procedure to
physicians.
David Rephun, ACT UP Boycott orga
nizer met with Hoffmann-La Roche repre
sentative Paul Oestreicher last week to
discuss activists' demands. Rephun
reported that Roche promised to stream
line the expanded access process soon.
But Rephun is concerned because Roche's
promises have gone unfulfilled before.
One day after this meeting, Oestreicher
told us that Roche had already filed a new
protocol with the FDA which will reduce
the case report forms from 6 pages to 2.
The FDA confirmed the filing. He also
said that Roche approached the FDA last
year for a National IRB, but was told that
the FDA did not have the same experi
ence with Roche as with Bristol Myers
and would not approve it. ACT UP coun
ters that the FDA says no such petition
was submitted.
The ddC expanded access program
has been fraught with controversy since
its inception last June. Initial criteria for
accessing the drag required that patients
be unable to take both AZT and ddl
(another experimental anti-HIV drug).
Hoffmann-La Roche eliminated the ddl
fail criteria in September after consider
able activist, physician and patient pres
sure.
Roche reports that 2,000 people are
receiving ddC through this program and
that 100 patients per week are being
added, contrasted with more than 12,000
people enrolled in the ddl expanded
access program. Roche’s Paul Oestreicher
says such comparisons are not valid, as
the Bristol Myers ddl program was in
place a year before the ddC program.
There are tens of thousands of people liv
ing with HIV who are not able to, or
choose not to, take AZT and could poten
tially benefit from ddC or ddl treatment.
But local physicians are frustrated.
Dr. Marlowe (principal investigator for
the AIDS Research Consortium of
Atlanta’s [ARCA] study comparing ddC
to AZT) said that he again spoke to
Hoffmann-La Roche last week asking
them to streamline the process for
expanded access.
Marlowe says he has not experienced
the long delay in getting the drag that
other physicians report. He speculated
that this may be due to Atlanta being an
experimental study site for the drug.
Amy Morris, Executive Director for
ARCA, said that ARCA physicians use
that institution's IRB approval. Dr.
Marlowe estimated that his patients have
been waiting 10 to 14 days for application
approval and then a week for the drag,
down from a 3 to 4 week delay at the
onset of the program.
It appears that an individual’s source of
medical care greatly impacts his or her
experience with ddC delays. One
NAPWA member reports that he waited
nine weeks for the drag. At the Grady
Infectious Disease Clinic, Nurse
Practitioner Gail Parker reported that she
began the paperwork process for a patient
last October and the patient has yet to
receive the drag. Delays were due to the
monstrous paperwork and the lengthy
process for IRB approval—Grady goes
through Emory’s IRB. She is hoping that
the second Grady patient she is currently
enrolling will move along more expedi
tiously. At another government funded
hospital no patients have been enrolled,
but an anonymous source there reported
that the patients, reviewed for eligibility
due to AZT failure, were then found ineli
gible due to other specific medical prob
lems.
Physician Toni Rossi has enrolled 10
patients into expanded access, but she has
an employee in her office specifically
assigned to complete the burdensome
paperwork. Rossi pointed out that while
Bristol Myers allows physicians to stock
the required forms to apply for ddl
expanded access, Hoffmann-La Roche
requires physicians to order the forms on
a case-by-case enrollment basis. Rossi
says her patients are getting the drag 2 to
3 weeks after the application is complet
ed.
ARCA's Morris has contacted
Hoffmann-La Roche several times on
behalf of ARCA physicians frustrated
with expanded access obstacles. She said
that the government has a responsibility to
address problems with expanded access
programs by outlining firm guidelines
which speak to issues about case report
forms, National IRB approval, incentives
for drag companies to establish such pro
grams and financial costs of the programs.
She reported that the U.S. Public Health
Service is circulating such guidelines cur
rently, but no one would give her any
definitive time table for adoption.
So, is anybody in Atlanta getting
ddC? Yes, some people have participated
in ARCA’s now closed ddC vs. AZT
study—although Grady reported no par
ticipants. ARCA is now enrolling
patients in a ddC vs. ddl study.
NAPWA is aware of a number of peo
ple purchasing ddC through buyers clubs.
The health care providers interviewed said
only a handful of patients reported pur
chasing the drag in this method. Buyers
club sources are: Fort Lauderdale (305)
568-3001; San Francisco (415) 626-2316;
Los Angeles (213) 748-1295.
Cost ranges from $50 to $70 for a
month's supply. In-stock supplies vacil
late. Each of these clubs reported that the
drug they are providing had been
analyzed for comparison against the
Hoffmann-La Roche drag.
Hoffmann-La Roche has, in fact,
begun the process of filing a New Drag
Application (NDA) with the FDA for
Market approval of ddC as both a single
agent and for combination therapy with
AZT. This means that the FDA will now
review all clinical data that has been gath
ered on both safety and efficacy to deter
mine if ddC can be sold as an anti-HIV
compound.
Roche’s Oestreicher says that the NDA
could be tens of thousands of pages and
will be completed by mid-year. The FDA
has promised a speedy review, but has
offered no timetable for actual approval.
Oestreicher declined to speculate about
what Hoffmann-La Roche would charge
customers for ddC.
Physicians interviewed were encour
aged that another anti-retroviral other than
AZT might be available by prescription
soon. Community based use and prelimi
nary results of trials investigating the effi
cacy of ddC in combination with AZT
have been widely reported in AIDS treat
ment news letters throughout the country.
The San Francisco-based "John James
AIDS Treatment News" reported in its
Nov. 23, 1990 issue on ACTG Trial 106.
In the trial 48 volunteers with AIDS or
ARC who had less than 200 T-cells took
various combinations of AZT and ddC.
This small study reported increased T-4
cells and weight gain with no new oppor
tunistic infections appearing after the first
few weeks of treatment. The O.I.'s that
did appear in the first few weeks may, of
course, have been developing prior to the
onset of the therapy.
Word is that the full data from the
study will be published in a medical peer
review journal next month. While this
small study offers some information on
combination therapy, further studies will
be necessary for conclusive proof.
Roche’s Oestreicher said that more than
500 patients have been enrolled in a
ddc/AZT combination study in the ACTG
system.
Dr. Rossi noted that combination thera
py was an interesting concept, but that she
had no experience with patients using
both drags together. Persons getting ddC
through expanded access programs are
not allowed prescriptions of AZT due to
AZT fail criteria.
Project Inform's Terry Beswick said
the implication of combination therapy
approval is astounding because it may
throw a monkey wrench into the whole
AZT standard-of-care model. It may mean
that all current drug trials using AZT sin
gle agent therapy would be revised for
AZT/ddC therapy. Project Inform initiated
a nationwide advocacy campaign to call
for early review of ddC and ddl data.
Beswick added that the information
put out by Hoffmann-La Roche indicated
that the NDA proposes "the use of ddC
for the treatment of AIDS and ARC
patients as an alternative to AZT therapy."
This description does not specify if the
drug company will indicate a T-4 cell
range for labeling. He speculated that it
may be restricted to people with 200 T-
cells or less as there may not be sufficient
data on people with 200-500 T-4 cells.
Physicians who wish to enroll patients
into ddC expanded access should call
(800)332-2144.
Anyone who wishes to sign on to ACT
UP's "Boycott Roche" campaign should
call (212) 532-3821 or stop by the
Atlanta NAPWA office.
Additional info on ddC studies is also
available at the NAPWA office, 98 6th
Street. 874-7926.
Southern Voice/March 28, 1991
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