[e-drug] AIDS drugs pipeline

[love@cptech.org]

E-DRUG: AIDS drugs pipeline
---------------------------------------
[crossposted from Pharm-Policy with thanks; NN]

This is a fairly readable summary of the drugs on the market and in the
pipeline for AIDS.  Several of the products in the pipeline will require
only a single dose once a day.   Jamie


http://www.hivandhepatitis.com/recent/misc/072301a.html

New Report Estimates HIV/AIDS Drug Market Will Triple in Value from $5
Billion in Annual Sales to $13 Billion in 2007
A recently published report by the financial services firm Griffin
Securities estimates that sales of HIV/AIDS drugs will grow from the
current level of $5 billion annually to $13 billion annually by 2007.

The report, published online at www.griffinsecurities.com/AIDS , offers
an summary of HIV/AIDS drugs in development. Printed here is the
report's executive summary, followed by the Table of Contents. To view
the entire document, click on the hyperlink above.

HIV/AIDS Industry Report:
Major Developments in the Treatment of AIDS

Executive Summary

The HIV market is expected to triple in size by 2007, growing from a $5
billion dollars in sales to over $13 billion in sales by 2007. Growth in
the HIV market will continue to be driven by a rapidly growing HIV and
AIDS population. In the absence of therapeutic intervention, the vast
majority of individuals infected with HIV will ultimately develop AIDS,
on average in about 10 years, which has a mortality rate approaching
100%. Experts say that the drugs currently available only extend life,
on average, 1.8 years.

As an immature market, new drugs and adjunct therapies with novel
mechanisms of action or unique resistance profiles are sorely needed in
the fight against HIV. Constant innovation, in terms of efficacy, side
effect profile and dosing are occurring. Current research and
development for HIV is focused on adjunctive therapy, which when
combined with existing HAART (Highly Active Anti-Retroviral Therapy)
regimens reduce side effects, enhance the efficacy of existing
treatments and delay the progression of the HIV virus.

The majority of these therapies are currently in clinical trials in late
stage patients, where existing HAART regimens fail, due to a build-up of
drug resistance and a worsening of immune response. Choosing a proper
salvage therapy remains a vexing problem in HIV treatment, particularly
for patients that have failed multiple Protease Inhibitors (PIs). It is
likely that salvage therapy will become more prominent going forward as
currently treated HIV infected patients develop resistance.

Today, there are 18 AIDS drugs on the market, falling into three general
classes: Nucleoside Reverse Transcriptase Inhibitors (NRTIs), Protease
Inhibitors (PIs); and Non-Nucleoside Reverse Transcriptase Inhibitors
(nNRTIs). These drugs are usually used in combinations of three or more
to create an effective antiviral therapy. In addition, almost 100
investigational new drug applications (INDs) have been submitted to the
U.S. Food and Drug Administration to conduct clinical trials on HIV
candidates.

GlaxoSmithKline (NYSE: GSK) continues to be the strongest franchise in
NRTIs, with Combivir®, Epivir®, Ziagen®, Retrovir®, and the most recent
Trivizir® dominating the market. Bristol-Myers Squibb's (NYSE: BMY)
Zerit® and Videx® also enjoy a formidable position, providing an
alternative to Combivir® in patients who have developed resistance.

In the near future, products from Triangle Pharmaceuticals (NADSAQ:
VIRS) (Coviracil) and Gilead Sciences (NASDAQ:GILD) (tenofovir) should
benefit from their favorable once daily dosing regimens, which optimize
compliance rates.

Protease Inhibitors (PIs), the second category of anti-viral drugs
currently on the market, are extremely powerful yet accompanied by
relatively strong side effects. About 10 percent of AIDS deaths now are
due to protease inhibitor-induced heart disease. Companies are working
to develop drugs that are more potent, less toxic and easier to take.

Merck & Co's (NYSE:MRK) Crixivan® continues to be the standard of care
in this class. Pfizer (NYSE: PFE) also continues to garner market share
with its extraordinarily successful Viracept®. A continued shift towards
PI sparing regimens like Dupont Pharmaceuticals' (NYSE:DD) nNRTI
Sustiva® and GlaxoSmithKline's (NYSE: GSK) NRTI Ziagen® and competitive
pressure from Abbott Laboratories'
NYSE:ABT) new PI Kaletra® is expected. An important potential PI in the
pipeline is Bristol-Myers Squibb's (NYSE: BMY) BMS-232632, which is
being tested for once daily dosing and is expected to be significantly
more potent than conventional agents with a favorable resistance
profile. Another potentially exciting PI entry may come from Tibotec,
that recently released data from an early study demonstrating an
extraordinary capability to block viral replication in-vitro across a
broad spectrum of multi-drug resistant HIV strains.

nNRTIs, the third category of currently approved anti-virals, continue
to be dominated by Dupont Pharmaceuticals' (NYSE:DD) Sustiva®. In
addition, Dupont Pharmaceuticals (NYSE:DD) has submitted a new drug
application to the FDA for new tablet formulations to simplify therapy.
Pfizer's (NYSE: PFE) nNRTI capravirine also appears promising for second
or third line therapy, appearing ten times stronger than nevirapine
[Viramune] or delavirdine [Rescriptor] against wild type virus.

Tibotec's TMC-120 also recently presented some very potent data,
demonstrating a 2-log drop in viral load within 7 days, at the top of
the scale compared with other HIV inhibitors, not just nNRTIs. Although
combination therapy has demonstrated the ability to slow resistance
development, resistant mutants have been identified to the drugs
currently used during the course of coactive therapy studies, and
cross-resistance among many agents has been increasingly recognized.
Even brief periods of non-compliance can reduce or eliminate the ability
of coactive therapy to suppress the virus, and may thus accelerate the
development of resistance. Once daily therapies should increasingly
become in demand.

Drugs in development like Triangle Pharmaceuticals' (NADSAQ: VIRS) NRTI
Coviracil, Gilead Sciences' (NASDAQ:GILD) NRTI tenofovir and
Bristol-Myers Squibb's (NYSE: BMY) protease Inhibitor BMS-232632, could
significantly benefit from their favorable dosing regimens, which create
the potential for once daily regimens to better optimize compliance
rates. Combination therapies should serve as effective defense
strategies in this environment. For example, GlaxoSmithKline's (NYSE:
GSK) Trivizir®, which combines three of its current NRTIs into one
tablet should benefit GlaxoSmithKline's (NYSE: GSK) NRTI market share.

There are dozens of other new candidates and new approaches at various
stages of development. They include entry inhibitors, immune based
therapies and vaccines.

Leadership in entry inhibitors include: Roche/Trimeris' (NASDAQ: TRMS)
fusion inhibitor T-20, Progenics Pharmaceuticals' (NASDAQ: PGNX) CD4
receptor blocker, PRO-542, and Aethlon Medical's (OTC: AEMD)
extracorporeal entry inhibitor, the HIV-Hemopurifier. These products
will be used in addition to, rather than instead of existing regimens,
and should serve to expand the overall market.

In the area of immunology, AIDS related immune-based therapies are
expected to include the use of immune stimulants or immune modulators
such as cytokines, to help expand the HIV-specific immunity. One such
example is Chiron's (NASDAQ: CHIR) IL-2, shown to increase CD4 cell
counts as various stages of HIV disease. Also, since latent virus
remains present in many cells and lymphoid tissues of the body, IL-2 may
also play an important role in "flushing-out" this hidden pool of virus.
Aethlon Medical's (OTC: AEMD) HIV-Hemopurifier may represent an adjunct
to such an IL-2 treatment, binding and capturing the newly exposed virus
in circulation, thus prolonging the useful period of standard HAART
regimens. Another interesting immune modulator in development is
Hollis-Eden Pharmaceuticals' (NASDAQ: HEPH) HE2000, which in its Phase
I/II trials, appeared to have beneficial effects in reducing viral load.

Finally, the worldwide demand and competition for an effective
preventive HIV vaccine is intense. It is logical to assume that
eventually, health organizations worldwide will be using combinations of
vaccine agents to limit the spread of HIV. Many new vaccine strategies,
preventive and/or therapeutic, which result in production of both
anti-HIV
antibodies and cytotoxic T-cells (CTLs), are now being pursued. VaxGen's
(NASDAQ: VXGN) vaccine candidate, AIDSVAX, is vying for the blue ribbon
as it completes Phase III trials this fall. CEL-SCI (AMEX: CVM) has also
completed several clinical studies with HGP-30 and HGP-30W that have
been quite promising. In particular, immunization with HGP-30 was shown
to protect against subsequent infection by HIV.


Table of Contents

1. EXECUTIVE SUMMARY
2. MUTATIONS AND RESISTANCE
3. NEW GOVERNMENT GUIDELINES
4. NEW DIRECTIONS

4.1. HIV ENTRY INHIBITORS

 T-20 -- TRIMERIS / HOFFMAN- LA ROCHE
 T-1249 -- TRIMERIS / HOFFMAN- LA ROCHE
 PRO-542 -- PROGENICS
 PRO-367 - PROGENICS
 PRO-140 -- PROGENICS
 FP-21399 - FUJI PHARMACEUTICALS
 SCH-1 - SCHERING-PLOUGH
 THE HIV-HEMOPURIFIER- AETHLON MEDICAL

4.2. IMMUNE-BASED THERAPY AND OTHER ADJUNCT APPROACHES

 RHIL-2 -- CHIRON / LIGAND PHARMACEUTICALS
 HE2000-- HOLLIS-EDEN PHARMACEUTICALS
 CCR RECEPTOR GENE -- HUMAN GENOME SCIENCES
 THE HIV-HEMOPURIFIER- AETHLON MEDICAL

5. VACCINE DEVELOPMENTS

 AIDSVAX -- VAXGEN
 ALVAC 1452 -- AVENTIS PASTEUR
 HGP-30W -- CEL-SCI
 NAKED DNA-- MERCK & CO
 TGAAC-09 -- TARGETED GENETICS
 PRECLINICAL -- GLAXOSMITHKLINE
 PRECLINICAL -- CHIRON
 TBC-3B -- THERION BIOLOGICS
 PRECLINICAL -- PROGENICS
 PRECLINICAL -- ALPHAVAX
 REMUNE -- PHASE II & III -- IMMUNE RESPONSE

6. ANTIVIRAL DRUGS: NRTIS, NNRTIS, AND PIS

REVERSE TRANSCRIPTASE INHIBITORS

6.1. NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NRTIS),
"NUKES"

APPROVED NRTIS

 RETROVIR® - GLAXOSMITHKLINE
 EPIVIR® - GLAXOSMITHKLINE
 COMBIVIR® - GLAXOSMITHKLINE
 ZIAGEN® - GLAXOSMITHKLINE
 TRIZIVIR® - GLAXOSMITHKLINE
 ZERIT® - BRISTOL-MYERS SQUIBB
 VIDEX® - BRISTOL-MYERS SQUIBB
 HIVID® - HOFFMAN-LA ROCHE

NRTIS IN DEVELOPMENT

 COVIRACIL -TRIANGLE PHARMACEUTICALS
 TENOFOVIR - GILEAD SCIENCES
 APD -TRIANGLE PHARMACEUTICALS

6.2. NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (nNRTIS)

APPROVED nNRTIS

 VIRAMUNE® - BOEHRINGER INGELHEIM / ROXANE
 SUSTIVA® - DUPONT PHARMACEUTICALS / MERCK & CO
 RESCRIPTOR® - PFIZER (AGOURON UNIT)

nNRTIS IN DEVELOPMENT

 CAPRAVIRINE (AG1549) - PFIZER (AGOURON UNIT)
 TMC-120 -- TIBOTEC GROUP
 DPC083 -- DUPONT PHARMACEUTICALS
 EMIVIRINE -- TRIANGLE PHARMACEUTICALS

PROTEASE INHIBITORS (PIS)

APPROVED PIS

 CRIXIVAN® - MERCK & CO
 VIRACEPT® -- PFIZER (AGOURON UNIT)
 KALETRA® -- ABBOTT LABORATORIES
 AGENERASE® -- GLAXOSMITHKLINE
 NORVIR® -- ABBOTT LABORATORIES
 FORTOVASE® / INVIRASE® -- HOFFMAN-LA ROCHE

PIS IN DEVELOPMENT

 BMS-232632- BRISTOL-MYERS SQUIBB
 TRIPANAVIR -- PHASE III - BOEHRINGER
 GW433908/VX-175 -- GLAXOSMITHKLINE
 TMC-126 -- TIBOTEC PHARMACEUTICAL
 ALUVIRAN (LOPINAVIR) -- ABBOTT LABORATORIES
 AG-1776 - PFIZER (AGOURON UNIT)

7. STATISTICS: THE SPREAD OF HIV EXCEEDS PREDICTIONS

HIV IN THE UNITED STATES

8. THE HIV LIFE CYCLE

9. CONCLUSIONS

10. GLOSSARY: APPROVED DRUGS FOR HIV/AIDS AND AIDS-RELATED
CONDITIONS

7/23/01

Source
Griffin Securities, Inc., 140 Broadway, New York, NY.

Copyright by Griffin Securities, Inc. (member NASD and SIPC) based in
New York City is a subsidiary of the publicly traded Cater Barnard Plc.
based in the U.K. Griffin (www.griffinsecurities.com) serves
corporations, institutions and individuals worldwide with a diverse
range of financial services including private capital markets; mergers &
acquisitions; financial advisory; brokerage and research. For more
information, please contact mail@griffinsecurities.com or call (212)
509-9500.
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