alan@garp.mit.edu (Alan Shaw) (10/02/89)
The Treatment & Data Digest
A Review of issues addressed by ACTUP's T&D committee
during its past week of activities
Number 14: September 25, 1989
GM-CSF AND PARALLEL TRACK: Members of T&D held their initial meeting with
Schering representatives Thursday to discuss putting GM-CSF on a parallel
track. Hugh D'Andrade, Executive Vice President in charge of Schering's biotech
portfolio, expressed concerns about the fate of patient accrual in their
placebo controled clinical trials should GM-CSF become available through
a parallel track. T&D noted that they _already_ have an accrual problem
in their trials precisely because of the placebo design. Other Schering
execs present claimed that since the size of the potential market for GM
is not yet known and the cost to manufacture the drug is so high, the
available supply is very small. Having been "burned" by their investment
in _Intron-A_ (their alpha-interferon product) for which the market turned
out to be disappointingly small, they will not scale up production of
GM-CSF until they are virtually certain of success. Other concerns expressed
were the costs/benefits to be realized through parallel track distribution
and the potential for legal liability.
It was also evident that they are keeping a close eye on the progress of
Bristol-Myers' experiment with parallel track. As we learned last Friday
(by the unanticipated delay in FDA's ddI Treatment IND approval for the
AZT intolerant), there remain a few refinements to be made in the definition
of the PT program (e.g. who will pay for the associated medical costs and who
will be given first dibs on the drug). Once it is clear to drug companies
such as Schering that the parallel track idea has FDA's -- and not just NIH's --
blessing, they may slowly begin to crawl out of the anachronistic abyss
holding them hostage to their own fears. The general tenor of the Schering
meeting seemed to indicate that if the Bristol experiment proceeds smoothly,
Schering would almost certainly give PT their earnest consideration.
A second meeting is slated to take place in two weeks.
(In a side note, D'Andrade indicated that Schering's GM-CSF partner,
Sandoz, would be even more recalcitrant than they about the idea of early
access to GM. It is important to note too, howeer, that the Schering/Sandoz
team is but one of several with cytokines (colony stimulating factors) in
clinical trials. AMGen's GM-CSF is consistently rumored to be near release
while the teams of Immunex/Hoechst-Roussel and Biogen/Glaxo also have
GM-CSF products in development.) More detailed information on GM-CSF and
other cytokines is available in T&D's _Glossary_ or _Treatment Agenda_
available at the T&D table at Monday night meetings.
THE DUBIOUS IMPORTANCE OF p24: HIV is made up of a number of different
proteins. The innermost (or "core") protein is called p24. ("p" for protein
and "24" for its size.) Usually p24 cannot be detected in blood test because it
is surrounded by the other HIV proteins (e.g. gp120 and gp41) within the virus.
During timed of heavy HIV replication the virus can become fragmented,
releasing the p24 antigen into the bloodstream, at which point it can be
measured.
It is hypothesized that during these periods of heavy replication the virus is
causing the greatest damage to the immune system. UNder this hypothesis,
then, someone who goes from p24 negative (i.e. p24 cannot be detected in the
blood) to p24 positive (p24 _can_ be detected in the blood) would be expected
to show a subsequent fall in T-4 cells. Conversely, a person who goes
from p24 positive to p24 negative would be expected to improve clinically.
Researchers have latched on to this phenomenon and incorporated p24 criteria
into many of their trial designs. But there is a problem with this. The
antigen p24 is present in only 20-30% of HIV-positive people. Many sero-
positives may _never_ become p24+. Yet the inclusion criteria of clinical
trials often mandate a positive p24 status. Obviously the theories
surrounding p24 need to be re-examined. While p24 might be useful in
monitoring the efficacy of antiretroviral therapies, it has yet to be
proven a reliable indicator of anything.
AN EVENING WITH DR. ANTHONY FAUCI: Dr. Fauci will be in town Thursday,
October 19 and would like to meet ACTUP's Treatment & Data Committee.
He will be talking about recent pathogenetic studies concerning the role
of EBV (Epstein-Barr virus) and CMV (cytomegalovirus) intransactivating
HIV. There will also be a time for general questions and answers.
Everyone from ACTUP is welcome to attend. Location to be announced.
AZT UPDATE: Although B-W's 20% reduction in the price of AZT is less
than satisfactory, it is nonetheless a step in the right direction.
(Let's keep a close watch out, though, to make sure they don't try to
make up the differential by hiking the price of acyclovir (brand name
_Zovirax_) as they did last time.) Furthermore, we must insist on the
release of the complete details of trials #016 and #019. And we have
to push FDA to change the labeling so that no one takes more than
600 mg/day. This means the comparative trials against ddI (#116 and
#117) _must_ compare it to only 600 mg of AZT.
TEACH-INS: T&D's first teach-in was held yesterday afternoon at the
Center. Next one is scheduled for Saturday, September 30 from 7-10 p.m.
at the Center. [208 West 13 St., N.Y.C.]
ELLEN COOPER: TURNCOAT? During deliberations of the Lasagna Committee
in Washington last week, Larry [Kramer] and Mark [Harrington] got a chance
to speak with Dr. Ellen Cooper (FDA's director of Antiviral Drugs) about
the plethora of flawed drug protocols. Seems she may be considering
allowing T&D to have a hand in the design of future drug trials. First
parallel track. Now protocol design. FDA has already assured us that
placebo control in trials of antiretrovirals is a thing of the past.
And there is no question that the participation of the AIDS community
in the design of trials would bolster accrual and expedite the entire
research process.
WORD OUT OF ALBANY is that neither the state nor the city looks at the
exact cause of HIV-related deaths. As a result, people are dying of
cryptosporidiosis, toxoplasmosis, PCP and MAI -- _all_ _preventable_
_conditions_ -- without anyone's knowledge. Women, babies and prisoners
go undiagnosed. AIDS deaths in women are frequently reported as the
result of pelvic inflammatory disease or cervical cancer. This skews
the direction of research as well as the distribution of funding.
Equally if not more heinous, Axelrod [NY State Health Commissioner]
says that no more hospital beds are needed in New York City. He claims
the perceived shortage is purely an administrative problem. So if Dave
[Axelrod] gets his way, we will see neither the balance of 311 beds approved
2 years ago not the 600 beds recently approved by Cuomo. Seems it's
high time to ACTUP in Albany.
A.D.A.P. TO COVER DHPG: New York's AIDS Drug Assistance Program (ADAP)
has historically refused to pay for DHPG as a treatment for CMV (cyto-
megalovirus) infections other than retinitis because the drug is so far
only officially approved for treatment against retinitis. But CMV is a
_systemic_ infection that can manifest itself in various places throughout
the body. It's good to hear that someone up in Albany is finally taking
the time to try to understand the real life issues we confront day to day.
For info on the ADAP program, call 1-800-542-AIDS.
IMPORTANT NUMBERS: AIDS Treatment Registry: information about trials in
the New York area: 212-268-4196. Project Inform: information on different
experimental treatments: 800-822-7422. National Trial Hotline: information
on trials throughout the United States: 800-TRIALSA. Bristol Myers ddI
Hotline: information on how to get ddI through the parallel track:
800-662-7999.