@rice.edu:MNSMITH%ECS.UMASS.EDU@icsa.rice.edu (Michael Smith) (08/03/89)
AIDS TREATMENT NEWS Issue #82, June 30, 1989
CONTENTS:
Compound Q Update
Fauci Proposes "Parallel Track" Treatment Access
ACT UP / New York Proposes National Research Agenda
New Drug Approvals: Aerosol Pentamidine, Ganciclovir
and Erythropoietin (EPO)
Montreal Conference Abstracts Now Available
COMPOUND Q UPDATE
by John S. James
Our previous issue included a last-minute report on a so-
called "unofficial study" of Compound Q -- actually a treatment
program and data monitoring project -- organized by San
Francisco's Project Inform and including over 30 patients and
nine physicians in four U.S. cities (San Francisco, Los Angeles,
New York, and Miami/Ft. Lauderdale), using a version of the drug
which is in common use in China. Probably no single story in the
AIDS epidemic has generated as much coverage in San Francisco's
major daily newspapers, the San Francisco Chronicle and San Fran-
cisco Examiner. Some of the information released by the San
Francisco press is available nowhere else. Local press coverage
has been even-handed and mostly sympathetic, despite vociferous
opposition from some researchers in the official Compound Q study
at San Francisco General Hospital. (A spokesperson for the Cali-
fornia Medical Association took a middle position, describing the
doctors involved as "respected physicians in the community work-
ing desperately to provide effective treatment and care," but
expressing serious concern about phase I -- dosage or safety --
studies being conducted outside of a university medical center).
We believe that a loud debate "for" or "against" the unoffi-
cial study would be unproductive, the wrong issue for furthering
the common fight against AIDS. The better question is what can
we learn from this extraordinary response to an extraordinary
situation. What can we learn about the drug, and also about how
to improve the official system of authorized research, to get
faster and better answers not only for AIDS but for other
diseases as well?
Project Inform and others involved in this treatment program
want to wait until it is finished, probably 30 to 60 days, to
make a full report. This article is based on news already
released but not widely available outside the San Francisco area.
Background
AIDS TREATMENT NEWS covered Compound Q in its issues of
January 13, April 21, May 5, and June 16; the last issue went to
press late and contained a news flash dated June 28. The active
ingredient of Compound Q is a protein called trichosanthin,
extracted from the root of a Chinese cucumber. The plant extract
must be highly purified before injection; otherwise it is highly
toxic and could be fatal. In the test tube, trichosanthin works
by selectively killing macrophages infected with HIV. Infected
macrophages are believed to be the major reservoir of the virus
in the body.
In China, trichosanthin is used to induce abortion, because
it selectively kills "trophoblast" cells, which line the uterus
during pregnancy. It is also used to treat choriocarcinoma, a
cancer of these cells, and may be better for this purpose than
any treatment available in the U.S.
Dr. Hin-Wing Yeung, a scientist from Hong Kong, suggested
trichosanthin as an AIDS treatment, based on earlier development
of the drug by researchers in Shanghai. Michael McGrath, M.D.,
at San Francisco General Hospital, first thought that the drug
might kill every macrophage in the body -- a radical but possible
treatment, as macrophages are normally replaced. In laboratory
tests, he unexpectedly learned that it killed only those cells
infected with HIV.
The Unofficial Study
About three months ago, before Project Inform was involved
with Compound Q, scattered groups of persons with AIDS, espe-
cially one group in Florida, had been able to obtain supplies of
the drug from China. Because this drug is more dangerous than
other non-approved AIDS treatments, the effort was made to obtain
some answers quickly about its safety and efficacy through a
highly professional treatment and data-monitoring program, before
patients were harmed by self-medication or other improper use.
At a press conference on June 28, Martin Delaney of Project
Inform explained the unofficial study, and the reason it was
done. We edited his comments for length:
"This treatment use (of Compound Q) is no different from
things like it that have been going on for the last five years.
What is different is that the media has turned this into a high-
profile event.
"Several points guided us and made us feel compelled to
organize this treatment program. One was impending community use
of this drug. Like other drugs before it -- like ribavirin, AL
721, dextran sulfate -- patients have ways to get these drugs
into the country legally. When there is hope about new drugs,
patients begin distributing and using them. Unfortunately,
widespread distribution and use has often taken place before we
had any sense of whether the drugs were safe, or whether they
worked.
"For example, in 1985 when ribavirin started coming into the
U. S. from Mexico, Project Inform was formed to ask the medical
community to set up prospective data monitoring on patients using
that drug. Nobody did so, and three years went by of use of that
drug, and the government ultimately concluded that it was not
useful, and might even be harmful in some patients. That's not an
intelligent way to run an epidemic.
"Now Compound Q is perhaps the most hopeful drug, but also
maybe a very toxic drug. Patients legitimately within their
rights are preparing to use it. Once again we have the specter
of hundreds if not thousands of people using a drug that we do
not know is safe or effective. Once again, it will take years to
get the answer by the standard methods.
"A hundred and fifty people a day are dying now because of
bureaucratic delays, because of inability to access important
drugs that are tied up in the pipeline. A good example is the
drugs DDI and DDC; their promise has been known since 1986. The
official researchers have now finished phase I testing on them,
and now they are telling us it will be two to two and a half more
years before efficacy tests are confirmed. AIDS patients don't
have that long to live. That's beyond the life expectancy of
most patients.
"We're already two and a half years into Compound Q, as
scientists learned the basic facts about it two and a half years
ago, and kept the information from us while there was a good
equivalent drug in China, a drug that had been used there for
nearly two decades.
"It is true that the ongoing official study of Compound Q
might have been done in six or nine months -- but it would not
provide the answers we needed to guide community use. It will
give limited answers about certain doses of the drug, one
administration only, in certain patients. We have to answer to
an entire community of people who are going to use the drug in
any way they see fit, unless guidance is given.
"It is not OK, it is not acceptable morally, to just turn
our backs and say, "You guys shouldn't do it," and feel that
we've done our job. We have to give guidance, if people are
going to have access to these drugs -- and they do have that
access, whether we want it or not.
"We also had experience going into this from people in
Florida. We were not the first ones to use Compound Q in a clini-
cal study. More than a dozen people in Florida had already used
the (Chinese) drug for HIV, before we even began talking about
doing what we are doing now. So we had considerable human
experience before going in.
"What did we do? First we talked to people working on impor-
tation. We asked them this time, let's not distribute the drug,
let's not sell it to people. Instead, let's try to channel it
into controlled clinical use, rather than the old system which
was pass it out and see what happens.
"We then collaborated to design a carefully controlled clin-
ical process under which patients would be treated. This is not
technically a study, it is a treatment program. People call it a
study because of the extent of scientific processes being used to
collect data from it. But the primary goal is treatment, not
research.
"For the protocol design, we called upon a researcher who
had run the research on another drug similar to trichosanthin,
called ricin-A, which has been used in more than a thousand
patients and is in the same family as trichosanthin. We used her
help in putting this protocol together, along with the experience
of the physicians involved. So the data gathering, the study
part of what we are doing, was based on an existing FDA-approved
study of the drug ricin-A; it is not something we made up.
"We also created an elaborate consent process to protect the
patients and the physicians alike.
"We then shared the protocol with other interested physi-
cians, pulled together a team of four groups in four cities,
looking to treat about 60 patients."
(The next section of the statement, omitted here, concerned legal
implications.)
"Baseline data was collected from all patients. Most of
them already had more than a year of extensive laboratory work.
After a complete workup, the patients were infused with a reason-
able quantity of the drug -- the smallest amount used for any
purpose in China. It is a fraction of the dose used in China
with cancer patients. It is a midpoint in the dose range pro-
posed for the trials at San Francisco General Hospital; in
another week they will have exceeded our dose. Our dose is the
midpoint of expected therapeutic doses based on laboratory data
-- and the dose used by more than a dozen patients in Florida.
It is a fifth of the dose that we've seen some patients use
self-medicated.
"Basic safety precautions were followed. The criteria for
entrance to this study were the criteria we lifted from San Fran-
cisco General's study. The same precautions were taken. Each
patient was administered a test dose of the drug in a tiny quan-
tity, to look for allergic reactions. They were followed for a
24 hour period of hospitalization, with vital signs taken con-
stantly. They were in the physician's office nearly daily for
the following week.
"Elaborate data gathering is going on, just as in a formal
clinical study. 14 full physicals, 14 complete work ups, blood
chemistry, urinalysis, sedimentation rates, P24 antigen and anti-
bodies, complete cellular immunity, all of what is being done in
virtually every AIDS clinical study in the country.
"Additional safety precautions include use of standard
adverse experience reporting forms that are approved by FDA,
standard side-effect ratings from FDA-approved studies, and com-
plete tracking of concomitant medications used. There is nothing
missing here in what has been done.
"The outcome to date is that the vast majority of the more
than 30 patients who have been treated in our treatment program
have tolerated the drug very well.
"We seem to have made an interesting, perhaps major
discovery about the effect of the drug on patients with HIV
infection of the brain. Two patients experienced mental confu-
sion, which cleared up in one to two weeks. And as you all know
one patient entered a coma, a coma that lasted no more than 24
hours and was in the process of complete resolution when the
incident occurred about a week later when the patient died.
"This patient vomited in his sleep and inhaled some of the
vomit, and had to be resuscitated. The evidence at the scene
suggested that the resuscitation process was quite successful,
his vital signs had returned to normal. However, the patient had
a living will, an agreement which called for no heroic measures,
which the family interpreted this as being, and the family asked
that the tube be pulled. It was the opinion of physicians on
site that had that not been the case, the patient could well be
alive today. We cannot say at this point if the problem was
related to the drug or not.
"At this time we are not making statements about whether the
drug is working. We have seen some interesting lab measures. But
it would be irresponsible scientifically to say that therefore
the drug is working. It will take time, to follow these patients
for a longer period and see if these results hold up. It would
give the wrong signal to our community to say we've concluded
that the drug works. We need more information before people
should start using this drug. The buyers' clubs and other groups
that work with patients are completely cooperative with this;
nobody is interested in endangering anyone.
"As to the future, there are questions we set out to answer
here to protect our community; we intend to get the answers to
those questions. The FDA has not shut us down; we do not know
whether they will try to or not. We think where we should go is
cooperation; we would like to collaborate, share our data with
the people in San Francisco General Hospital and the Food and
Drug Administration. That was the intention all along; and until
the incident last week, they shared in that intention. We had
discussed sharing data submissions, about the interaction of our
data with theirs. It was only after this very unfortunate death
that people headed for the hills.
"We intend to present our data to the Food and Drug Adminis-
tration, the National Institutes of Health, and the medical jour-
nals. If the data suggests that the drug is useful, we will
fight for early access to it on behalf of AIDS patients. And
whatever the outcome, we will continue to press for faster
action. It is unconscionable to accept five and a half years'
typical time for the development of drugs for AIDS, when patients
have an average lifespan of only two years. We have fought long
and hard battles in Washington to improve this process, we think
progress is being made, but it isn't being made fast enough."
Neurological Side Effects: Bad News or Good?
As Delaney mentioned in the press conference above, a hand-
ful of patients with dementia or other evidence of HIV infection
of the brain suffered neurological side effects -- a period of
mental confusion lasting one to two weeks for two patients, or a
coma lasting less than 24 hours for one other.
Although no one knows for sure, it seems likely that the
neurological effects may be evidence that the drug is doing its
job -- not a sign of toxicity.
What Delaney had heard from experts familiar with the study
is that HIV does not infect neurons in the brain, but rather
glial cells -- supporting cells which the body can replace. The
neurological effects seem to be a temporary result of killing a
large number of infected cells at one time. If so, Compound Q
might prove helpful for persons with HIV brain infection. It may
need to be given in smaller doses at first, to control the side
effects.
Further studies will be needed to answer this question.
Meanwhile, because of the unknowns and risks involved, physicians
are screening patients for evidence of HIV brain infection,
because of the increased risk of treating them with Compound Q
until more is known.
The Future
The unofficial Compound Q study will end in 30 to 60 days.
Until the results are reported, we will not know whether the drug
is useful for treating AIDS or HIV, or not.
Readers should realize that there are other side effects,
dangers, and precautions not touched on in this article. No one
should use Compound Q without expert medical supervision.
What lessons have been learned? Medically, the unofficial
study has taught researchers more in the last few weeks about
Compound Q as a human treatment for HIV than had ever been
learned before. And according to Delaney, the official study at
San Francisco General Hospital has already used this information
to skip some of its low test doses, which are now unnecessary.
One result of the unofficial study, therefore, is that the offi-
cial trials will produce results sooner -- a major purpose of the
unofficial treatment program all along.
Even more importantly, the unofficial Compound Q study is
demonstrating that it is possible to get useful results quickly,
if a research project is organized for that purpose. How is Pro-
ject Inform's program getting useful results in only four or five
months, while official trials take five years or longer to do the
same?
A look at specifics of the trials will show part of the
answer. The official Compound Q was kept secret for at least a
year and a half, between May 29, 1987 when the patent application
was filed for anti-HIV use of trichosanthin, and January 3, 1989
when the patent was granted. During this time a new method for
extracting the drug from the Chinese cucumber root was developed.
Then after the patent was granted, it took six months to get
phase I tests going; and these tests are slow because phase I
tests were designed for new chemical never given to humans
before. The Chinese experience was ignored.
In contrast, the unofficial study used the drug and medical
information already existing in China. It proceeded immediately
with a dose well known in human use and projected, based on
laboratory data, to be therapeutic for HIV. By doing so, instead
of developing a new patentable technology requiring new animal
tests and phase I human trials, it avoided two years or more of
delay. Note that this study could have been carried out two
years ago, exactly as it is being done today, if the anti-HIV use
of trichosanthin had not been kept secret during that time. As
far we know, the intervening two years of official research added
little or nothing to the unofficial study, which is based on
pre-existing medical technology from China, not on the new tech-
nology created during the patent hiatus.
After the patent was granted on January 3 of this year,
there was little media interest until April 15, 1989, when an
article on Compound Q (also called GLQ 223) was published in the
Proceedings of the National Academy of Sciences.
Another delay in the official research track is illustra-
tive. After the patent was granted in January, it took some time
for Genelabs, the developer of Compound Q, to get an IND (Inves-
tigational New Drug approval, meaning approval to test the drug
in humans) from the FDA. We cannot know the full story of this
delay, but we do know that at one point a San Francisco TV
reporter called the FDA to ask why the IND had not been granted
for this drug, and was told that the FDA had no application for
the IND on file! Genelabs said that it had applied. Because of
a misunderstanding, each party was waiting for the other.
Apparently the FDA believed that what Genelabs had submitted was
only a draft, not an official application -- while Genelabs
thought it had applied and was waiting for approval to begin the
clinical trial at San Francisco General Hospital. We are all
lucky that a chance call from a reporter straightened out this
snafu, which had put the entire world's research program for one
of the two most promising AIDS drugs on hold.
This kind of problem seems surprising only to the unini-
tiated. In our three years of covering AIDS treatment research,
we have seen such mindless delays happen again and again. The
difference is that usually there is no public interest in the
details of the process, and nobody there to make the call or do
what else may be needed to straighten the problem out.
For too long the public has accepted a stock answer that
clinical research is going as fast as possible, that the delays
are caused only by the requirements of good science. But
analysis of what is actually happening shows that the system can
be vastly improved.
In the field of industrial quality assurance, there are
trained, professional specialists to solve just this kind of
problem. If a company is taking too long to get its products
developed, for example, it can hire experts to analyze what is
happening and suggest solutions. Typically the problems are due
to flaws in the system, not to faults of the individuals
involved, as no one person alone may have the power and resources
to produce results. Instead, the system must be improved, by
identifying the problems and correcting them. Academic experts
in quality assurance can and should be invited onto the team to
examine how trials might be organized to get faster results, con-
sistent with good science.
The unofficial study of Compound Q organized by Project
Inform is now producing the most important results -- practical
information about whether, when, and how to use the drug -- about
ten times faster than the official research system has been able
to do so, either for Compound Q or for other drugs.
Admittedly there are greater risks to the patients in an
accelerated study. Some patients want a role in making this
decision, however, in balancing the risks of using a new treat-
ment against the risks of doing nothing. Some may also want to
contribute to the benefit of others, realizing that tens of
thousands of lives are likely to be saved if an accelerated study
shows unequivocally that a drug is helpful, months or years ahead
of the official trials.
The take-home lesson, we believe, is not to blame individu-
als, on either side. Nor do we believe that the official system,
with its safeguards and protections for research subjects, should
be abandoned. Instead, we should reform the official system of
clinical trials to make it faster and more efficient. If this
can be done, there should be no need for bypassing the system in
the future.
The right approach to reform is a win-win approach.
Nobody's interest needs to be sacrificed -- and certainly the
quality of scientific workmanship need not be reduced. Instead,
careful, professional analysis and negotiation can find intelli-
gent ways to make the system work better.
Who can implement this approach? Ultimately the only force
which can do so is a professional consensus in the medical and
research communities. Without that consensus, no one else -- not
the AIDS community, not the FDA, the NIH, the White House, or the
pharmaceutical industry -- can make it happen.
What if the consensus is not there? Physicians and scien-
tists prize their independence; no one can tell them what to do.
But we can appeal to their intelligence. The AIDS community can
investigate and analyze exactly what is happening, and illuminate
precisely what the problems are, what their consequences are, and
what should be happening instead. Usually we cannot implement the
reforms by ourselves. But we can make the problems and the
opportunities for improvement so obvious that they cannot be
ignored.
*****
FAUCI PROPOSES "PARALLEL TRACK" TREATMENT ACCESS
Anthony Fauci, M.D., the head of the largest AIDS clinical
trials program at the U.S. National Institute of Allergy and
Infectious Diseases, proposed a "parallel track" system whereby
patients not able to enter clinical trials would be allowed to
use some drugs which had passed safety tests but had not yet com-
pleted efficacy testing. The proposal, made public June 23 at a
talk in San Francisco, was prominently reported in The New York
Times and other newspapers the following Monday, June 26.
Although no new laws are required, Dr. Fauci stressed that
this plan would work only if the FDA, the drug companies
involved, and the scientists running the trials agreed. He can-
not make it happen by his decision alone.
The way the plan could work is that when a clinical trial is
being designed, the parties involved -- the FDA, the drug com-
pany, and NIAID -- would discuss whether a parallel track could
be implemented. If all agreed, then the study protocol could
specify that certain patients not eligible for the trial could be
treated with the drug through the parallel track. Examples of
those ineligible might be persons who had used AZT but had to
stop because of the toxicity, if the particular trial excluded
people who had ever used AZT. Others might be allowed in the
parallel track because the study was full, or because there was
no trial available in their area. Fauci emphasized that this
parallel access must not interfere with the main trial needed to
get scientific data about the drug -- presumably meaning that
those able to enter the trial would not be allowed to choose
parallel-track access instead.
At a press conference after his San Francisco announcement,
Fauci suggested that the parallel track would also be designed to
collect data useful for evaluating the drug -- and that
community-based clinical trials might be ideal for conducting
such studies.
Discussions on possibly implementing a parallel track are
now going on with the FDA and with several drug companies.
Comment
We commend Dr. Fauci for an excellent proposal, which could
speed both access to drugs and final approval. However, there
are important obstacles which might prevent the idea from being
carried out.
For a parallel track to happen, three organizations must
agree: Fauci's NIAID (if the trial is in the NIAID system), the
FDA, and the pharmaceutical company which owns the rights to the
drug. NIAID will be no problem, and the FDA seems willing to
accept the idea, at least if the parallel track is able to gen-
erate scientifically sound data, as well as providing treatment
access to the drug.
Most people familiar with the parallel-track concept think
that the biggest problem will be with the drug companies. They
will probably be expected to pay for the parallel track -- since
the government will not want to pay for it, and there would be
problems in allowing patients to do so. The question, then, is
what incentives the companies have to support this access to
their drug?
What drug companies want above all is approval of their NDA
(New Drug Application), meaning final permission to market the
drug. If the parallel track will generate data likely to help
them get the NDA sooner, then most companies will probably be
willing or eager to have a parallel track when their drug is
tested.
The key to the parallel track therefore depends on the FDA.
If the FDA only halfheartedly permits it, then drug companies
will know that paying for treatment access will do little or
nothing for them in getting their drugs approved, and they will
not agree. But if it is clear that the parallel track can col-
lect data which the FDA is likely to accept as supporting the
NDA, then the idea can work.
And even aside from the question of whether the parallel-
track idea is ever implemented, the fact that Fauci proposed it
has already furthered debate and consensus-building around the
issue of earlier access to treatment for life-threatening condi-
tions. For example, in private discussions of the idea before
its public announcement, Fauci heard objections that drug com-
panies would not accept the parallel track because they were
afraid that what happened to Syntex with ganciclovir would happen
to them. Syntex provided the drug free to thousands of patients
on a compassionate basis, saving them from blindness, and it has
been widely believed in the pharmaceutical industry that they
were punished by the FDA for doing so. Fauci answered these
objections by clarifying that Syntex got into trouble not for
providing compassionate access to persons with AIDS, but for
failing to conduct clinical trials early.
Fauci's suggestion is important in another way. As the U.S.
government's leading AIDS researcher, he is the one most clearly
qualified to challenge the unfortunate idea that providing wider
access to treatment will make scientific trials difficult or
impossible. By so doing he removes the issue from the realm of
science, which most people consider themselves incompetent to
think about, to the realm of cost and feasibility, where the pub-
lic can address the issues on their merits.
*****
ACT UP / NEW YORK PROPOSES NATIONAL RESEARCH AGENDA
At the June 4-9 V International Conference on AIDS in Mont-
real, ACT UP / New York released "A National AIDS Treatment
Research Agenda", a 16-page document proposing public-policy
changes in treatment research. The authors, in ACT UP's Treat-
ment + Data Committee, are very well informed not only about new
medical developments, but also about the procedures and politics
of the Federal agencies and other organizations involved.
It is impossible to summarize this proposal adequately; but
to give an idea of its scope, we will list the "12 Principles for
a New AIDS Drug Testing System", which makes up one of the
document's four sections. Note that the document contains expla-
natory material about each of these principles; it had to be
omitted here because of limited space. The 12 principles:
1. People with AIDS, HIV, and their advocates must partici-
pate in designing and executing drug trials.
2. A comprehensive, coordinated, compassionate drug
development strategy must ensure that all promising agents are
evaluated thoroughly and, if found effective, distributed
rapidly.
3. Resources must be focused on drugs which treat or
prevent opportunistic infections, not just on antiretroviral
drugs.
4. End the exclusion of women, poor people, people in rural
areas, people of color, drug users, prisoners, hemophiliacs and
children from experimental treatments. Expand staff and facili-
ties in areas with high concentration of HIV-infected people so
trials can take place there.
5. End the exclusion of AZT intolerant individuals from
trials for infections or other antivirals.
6. Protocols should be flexible enough to accommodate new
knowledge about HIV infection, allowing subjects to receive
state-of-the-art care for opportunistic infections (OIs) as such
standards evolve.
7. Trials must be designed for the real world: prophylaxis
permitted, placebos avoided, efficacy criteria and endpoints
humane.
8. Clinical costs associated with trials and not paid for
by sponsors should be funded by third party payors to insure that
personal income is not a de facto exclusion criterion.
9. The Orphan Drug Act should be reformed so that products
developed at public expense are priced fairly. In return for its
multimillion-dollar investment in AIDS research, the government
is entitled to demand low-cost drugs for AIDS. This will make
treatments accessible to people who can't afford AIDS drugs in
both the US and worldwide.
10. The community-based clinical trials network, NIH, FDA
and other drug development agencies require increased staff,
funding and facilities to wage a successful effort against AIDS.
11. Establish an accurate, up-to-date, accessible interna-
tional directory of clinical trials and promising experimental
treatments for HIV and for AIDS-related opportunistic infections.
12. Promising new treatments for HIV and AIDS-related
infections should be made accessible to anyone without regard to
personal income.
Another section of the document, "AIDS Clinical Research
Priorities," lists "5 Drugs We Need Now" (DDI, EPO [already
approved -- see below], fluconazole, foscarnet, and GM-CSF), and
"7 Treatments We Want Tested Faster" (ansamycin, CD4-exotoxin,
CD4-immunoadhesin, diclazuril, hypericin, passive immunotherapy,
and peptide T). A short description is given for each drug.
Other sections of the proposal are "New Models for Clinical
Trials," and "AIDS Drug Development Disasters."
For a copy of the proposal, send a self-addressed #10 or
larger envelope with two ounces postage to:
Mark Harrington
611 E 11th St., Apt. 7A
New York, NY 10009
*****
NEW DRUG APPROVALS: AEROSOL PENTAMIDINE, GANCICLOVIR, AND
ERYTHROPOIETIN (EPO)
This month the FDA approved three drugs important in AIDS
treatment.
Aerosolized Pentamidine
On June 15 the FDA gave full approval to LyphoMed Inc. of
Rosemont, IL for marketing aerosolized pentamidine to prevent
pneumocystis -- not only for patients who have already had pneu-
mocystis, but also for anyone who has T-helper cell counts of 200
or less. The drug already had "treatment IND" status -- official
approval for early release of a treatment for a serious or life-
threatening condition -- but some insurance companies had used
lack of final marketing approval as an excuse to deny reimburse-
ment. The new approval announced this month should make it pos-
sible for many more patients to obtain the drug.
Ganciclovir
On June 26, Syntex Corporation of Palo Alto, CA announced
that the FDA had approved ganciclovir for treatment of CMV retin-
itis in persons with AIDS or other immune deficiencies. This
approval resulted from negotiated compromises to end the very
difficult situation of this drug (see AIDS TREATMENT NEWS #71,
December 16, 1988). This case, now hopefully behind us, made it
much more difficult for persons with AIDS to receive compas-
sionate use of other drugs.
The current approval will also allow physicians to prescribe
ganciclovir for other CMV infections, such as colitis or pneu-
monia, although efficacy has not been officially established for
these illnesses. Physicians may be reluctant to prescribe the
drug for these "off label" uses, and insurance companies may
refuse to pay.
The approval also removes an obstacle to research with other
CMV treatments. Because it is unusual to get permission to use
more than one experimental drug in the same trial, it would have
been difficult to test other treatments such as foscarnet using
ganciclovir as a control group. But since it was generally
accepted that ganciclovir was effective, it was not ethical to
use a placebo, either. Since no drug was approved for CMV, and
yet one was generally known to work, it was not possible to have
a control group for efficacy tests of any other potential treat-
ments. The new approval should break this research deadlock.
Erythropoietin (EPO)
Because this treatment for anemia has been involved in com-
plex contract and pricing disputes, the drug has two separate
approvals at this time. One will make it available to some per-
sons with AIDS at no cost. The other makes it available to any
patient who needs it, for AIDS or other conditions, but the offi-
cial indication is only for kidney disease, so insurance com-
panies will probably refuse to pay for other patients under that
program.
The AIDS-related approval is a "treatment IND" obtained by
Ortho Pharmaceutical Corporation, for its brand of EPO, Eprex.
According to Ortho, the treatment IND was granted after earlier
trials showed that the drug reduced anemia, and eliminated the
need for transfusions in two thirds of the patients using it.
EPO is used to treat anemia caused by AZT, or anemia caused
directly by HIV.
At this time the AIDS patients eligible to receive EPO under
the treatment IND must have a hematocrit less than 30 percent,
and less than 500 mu/ml of EPO in their blood. (EPO is a hormone
found naturally in the body.) They must also be patients of one
of the 30 physicians who are already part of Ortho's EPO program.
The company plans to enroll other physicians later.
Meanwhile, any physician can prescribe EPO for any patient
who needs it, under an earlier (June 1, 1989) full marketing
approval given to Amgen Inc (a competitor of Ortho Pharmaceuti-
cal) for Epogen, its brand of EPO. But since the official appro-
val for this brand is only for kidney disease, the cost of this
very expensive drug will probably not be reimbursed when it is
used to treat anemia from other causes.
*****
MONTREAL CONFERENCE ABSTRACTS NOW AVAILABLE
Project Inform will copy and mail the published abstracts of
thousands of submissions to the V International Conference on
AIDS in Montreal. The abstracts can be dense reading for non-
medical people, but are usefully organized into sections discuss-
ing epidemiology and public health, clinical aspects, basic
research, AIDS and the individual, AIDS, society and behavior,
ethics and law, international issues, and the economic impact of
AIDS. These abstracts do not include most of the oral sessions,
however, where some of the most important work was presented;
video or audio tapes of most of these conference sessions are
available through other services.
For a copy of the abstracts only -- over 1,200 pages of fine
print -- send $100 U.S., or $125 Canadian, to: Project Inform,
347 Dolores Street, Suite 301, San Francisco, CA 94110.
STATEMENT OF PURPOSE
AIDS TREATMENT NEWS reports on experimental and complementary
treatments, especially those available now. It collects informa-
tion from medical journals, and from interviews with scientists
physicians, and other health practitioners, and persons with AIDS
or ARC.
Long-term survivors have usually tried many different treatments,
and found combinations which work for them. AIDS TREATMENT NEWS
does not recommend particular therapies, but seeks to increase
the options available.
We also examine the ethical and public-policy issues around AIDS
treatment research.
HOW TO SUBSCRIBE TO AIDS TREATMENT NEWS BY MAIL
Send $100.00 per year for 26 issues ($150.00 for businesses and
organizations), or $30.00 reduced rate for persons with AIDS or
ARC who cannot afford the regular rate, to: ATN Publications,
P.O. Box 411256, San Francisco, CA 94141. A six-month subscrip-
tion (13 issues) is $55.00 ($80.00 for businesses or organiza-
tions), or $16.00 reduced rate. For subscription information and
a sample issue, call (415) 255-0588.
For the complete set of over 70 back issues, send $75.00 ($18.00
for persons with AIDS or ARC) to the above address. The back
issues include information on hypericin, dextran sulfate, foscar-
net, passive immunotherapy, DTC (Imuthiol), naltrexone, DHEA,
lentinan, propolis, coenzyme Q, monolaurin, egg lecithin lipids,
fu zheng herbal therapy, DNCB, aerosol pentamidine, fluconazole,
ganciclovir (DHPG) and other experimental or complementary treat-
ments.
To protect your privacy, we mail first class without mentioning
AIDS on the envelope, and we keep our subscriber list confiden-
tial.
Outside North America, add $20.00 per year for airmail postage,
and $18.00 airmail for back issues. Outside U.S.A., send U.S.
funds by International Postal Money Order, or by travelers
checks, or by drafts or checks on U.S. banks.
Copyright 1989 by John S. James. Permission granted for non-
commercial reproduction.