New Medicines for AIDS in Development

DEC 19 '95 08:26AM PHRMA

P.1/16

NEW MEDICINES
IN DEVELOPMENT
FOR AIDS
Presented by the Pharmaceutical Research and Manufacturers of America
1995 Survey
AIDS Research Pmmiing.11O Medicines in velopment

his year's Nw Medicines in
Development for AIDS report
includes 34 drugs and vaccines
that are appearing for the first time. The
new therapies include two anti-cancers, four
anti-infectives, 18 antivirals, two immunomodulators, four vaccines and two genetherapy vectors. Since last year's survey, in
November 1994, the Food and Drug Administration (FDA) has given marketing approval
to two medicines that were included in last
year's survey--Gamimune-N (Bayer) and
WinRho SD (Univax)-and approved an
additional indication for ganciclovir
(Cytovene, Roche Bioscience).
Most recently, FDA's Antiviral Drugs
Advisory Committee has recommended
approving the first of a new class of AIDS
drugs called protease inhibitors. This group
includes:
* Saquinavir (Invirase, Hoffmann-La
Roche). The advisory panel recommended
expedited approval for saquinavir to be used
in combination with the currently available
group of anti-AIDS drugs, known as nucleoside analogues, to increase overall therapeutic effectiveness and prevent or delay the
development of drug resistance.
* Indinavir sulfate (Crixivan, Merck).
Indinavir has advanced to Phase III clinical
trials, the last development stage before
submission to FDA of an application for
marketing approval.
* Ritonavir (Abbott Laboratories) This
drug is also in Phase III trials.
* Viracept (Agouron Pharmaceuticals).
Viracept is in Phase II trials.
The FDA Antiviral Drugs Advisory
Committee also recommended approval of
the nucleoside analogue lamivudine (Epivir,
Glaxo Wellcome), more commonly known as
3TC. Lamivudine and stavudine (Zerit,
Bristol-Myers Squibb), also known as d4T,
appear to increase the effectiveness of
AZT---zidovudine (Retrovir, Glaxo
Wellcome), the first nucleoside analogue--
when the drugs are administered together.

1995 AIDS MEDICINES/VACCINES IN DEVELOPMENT

Anti-cancers
Anti.infectives

11
14

Antivirals 54

Gene Therapy
Immunomodulators
Vaccines
Others

03
12
14
-7

Investigators have found that combinations of other nuclcoside analogues could be
more effective than any one of them administered alone. Also, their effectiveness
sometimes increases when they are combined with other antivirals that are not
nucleoside analogues, such as acyclovir
(Zovirax, Glaxo Wellcome), or with alpha
interferon (Wellferon, Glaxo Wellcome).
Non-nucleoside inhibitors of a key
enzyme required for HIV replication--
reverse transcriptase--are also in late-stage
clinical trials. Some of these include:
* Delvaridine mesylate (Rescriptor,
Upjohn), one of a class of non-nucleoside
inhibitors known as BHAP compounds,
which is in Phase III trials; and
* Nevirapine (Viramune, Boehringer
Ingelheim), which is currently in Phase
II/III trials.
Several gene-therapy clinical trials are
under way in HIV-infected patients. In
these tests, genes are carried into T-cells by
an inactivated retrovirus to increase the
body's capacity to recognize and destroy the
AIDS virus. The clinical trials include:
* A Phase II trial of an intramuscularly
injected retroviral vector produced by
Viagene, involving more than 200 patients
in 15 clinical centers;
* A Phase 111 trial by Cell GeneSys and
NIAID of killer T-cells modified to express

HWIV-specific receptors, enabling the cells to
recognize and destroy HIV-infected cells; and
* A Phase I trial of HyTK retrovirus by
Targeted Genetics in HIV-positive patients
undergoing bone-marrow transplants.
Thirteen AIDS vaccine trials are being
conducted in humans, including
* A Phase III trial of a therapeutic vaccine by Immune Response Corporation.
* Phase II trials of AIDS vaccines as
therapeutics by Immuno Clinical Research
and MicroGeneSys.
PhRMA is grateful to the 35 organizations that have joined in presenting this
survey on medicines in development for
AIDS. They are listed on the back of this
report.
America's pharmaceutical industry will
spend $15 billion this year on the search for
new medicines, including new drugs and
vaccines for AIDS and its relatcd conditions. This research must continue without
interruption so that it can produce more
effective treatments and even a cure for
this terrible disease.
Gerald J. Mossinghoff
PhrAident
PhRMA