News (Updated February 15,
2003)
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| Press Release | Source: Roche; Trimeris |
Monday February 10, 7:29 am ET
Unlike existing anti-HIV drugs that work inside the cell, FUZEON and T-1249 have a unique mechanism of action that is designed to block HIV before it enters the human immune cell. Consequently, FUZEON and T-1249 are active against HIV that is resistant to the currently available classes of anti-HIV drugs.
Presentations on FUZEON
In the studies, treatment-experienced patients receiving FUZEON plus an individualized regimen of standard anti-HIV drugs were twice as likely to achieve undetectable levels of HIV in the blood (less than 400 copies/mL) as patients who received an individualized drug regimen without FUZEON (32.7% vs. 15%).
The response of patients in the FUZEON arm surpassed that of patients taking an individualized regimen alone across all subgroups studied, including age, race, baseline immune cell (CD4) count and baseline viral load. In both treatment arms, greater viral suppression was seen in patients who had more active agents in their individualized regimen, less treatment experience and less advanced disease (CD4 count greater than 100 cells/ul). The combined safety analysis included a safety update with patient exposures for longer than 24 weeks. This analysis focused on further characterizing injection site reactions and combining similar and clinically equivalent adverse event terms to identify any relevant differences between treatment arms. Injection site reactions are the most common adverse event associated with FUZEON. Injection site reactions occurred in almost all patients receiving FUZEON; most had mild to moderate pain or discomfort that did not require analgesics or limit usual activities. While the overall incidence of bacterial infections was similar across both treatment arms when adjusted for time of exposure to the individualized regimen, bacterial pneumonia was observed at increased frequency in patients in the FUZEON arm compared to patients taking an individualized regimen alone (4.5% vs. 0.3%).
More About FUZEON
FUZEON, a fusion inhibitor, is administered as a twice-daily subcutaneous injection. Local injection site reactions were the most frequent adverse events associated with the use of FUZEON. In Phase III clinical studies, 98 percent of patients had at least one local injection site reaction. In this treatment-experienced patient population, three percent of patients discontinued treatment with FUZEON as a result of injection site reactions.
The addition of FUZEON to background antiretroviral therapy generally did not increase the frequency or the severity of the majority of adverse events. There was less than five percent difference in the most common adverse events seen between FUZEON plus an individualized regimen of antiretroviral drugs and individualized regimen alone. In addition to those mentioned above, the most common adverse events seen more frequently in patients receiving FUZEON plus an individualized regimen than in patients who received treatment without FUZEON were headache, peripheral neuropathy, dizziness (excluding vertigo), insomnia, depression, appetite decrease, asthenia, myalgia, constipation and pancreatitis. The majority of adverse events were of mild or moderate intensity.
Presentation on T-1249
New data from a short-term study (T1249-102) reveal that T-1249, the second-generation fusion inhibitor, significantly reduced levels of HIV in the blood in most patients who exhibited detectable viral replication while receiving an individualized anti-HIV drug regimen that included FUZEON.
This study evaluated the antiviral activity and safety of T-1249 over a 10-day period in 25 patients who were participating in Phase II or Phase III studies of FUZEON and who exhibited HIV RNA levels between 5,000 and 500,000 copies/mL at two consecutive clinic visits while on treatment with FUZEON. Patients in this study discontinued FUZEON and added T-1249 to an unchanged individualized anti-HIV drug regimen. The median HIV RNA decline from baseline after 10 days of treatment was 1.1 log10. There were no serious adverse events judged possibly to be related to T-1249 in the trial. The results from this study demonstrate that fusion inhibitors constitute an expanding class of antiretroviral drugs with the potential to be used sequentially.
More About T-1249
In an earlier Phase I/II clinical trial of T-1249, no treatment-related, clinically important laboratory abnormalities occurred and no dose-limiting toxicities were identified. Three serious adverse events possibly related to T-1249 occurred: grade 4 neutropenia (25 mg QD), hypersensitivity reaction (25 mg BID), and fever associated with injection site reaction (150 mg QD).
Roche in HIV
Roche is at the forefront of efforts to combat HIV infection and AIDS, committed for 15 years to groundbreaking research and development of new drugs and diagnostic technology. The objective is to provide tailored treatment solutions and an improved standard of care worldwide for those people living with HIV.
About Roche
Hoffmann-La Roche Inc. (Roche), based in Nutley, N.J., is the U.S. prescription drug unit of the Roche Group, a leading research-based health care enterprise that ranks among the world's leaders in pharmaceuticals, diagnostics and vitamins. Roche discovers, develops, manufactures and markets numerous important prescription drugs that enhance people's health, well being and quality of life. Among the company's areas of therapeutic interest are: dermatology; genitourinary disease; infectious diseases, including influenza; inflammation, including arthritis and osteoporosis; metabolic diseases, including obesity and diabetes; neurology; oncology; transplantation; vascular diseases; and virology, including HIV/AIDS and hepatitis C.
For more information on the Roche pharmaceuticals business in the United States, visit the company's Web site at: http://www.rocheusa.com.
About Trimeris, Inc.
Trimeris, Inc. is a biopharmaceutical company engaged in the discovery and development of novel therapeutic agents for the treatment of viral disease. The core technology platform is based on fusion inhibition aimed at treating disease by preventing viruses from entering host immune cells. Trimeris has two anti-HIV drug candidates in clinical development. FUZEON, currently in Phase III clinical trials, is the most advanced compound in development. A New Drug Application (NDA) and Marketing Authorisation Application (MAA) have been submitted for FUZEON with the US FDA and the EU EMEA, respectively. Trimeris' second fusion inhibitor product candidate, T- 1249, has received fast track status from the FDA and is in Phase I/II clinical testing. Trimeris is developing FUZEON and T-1249 in collaboration with F. Hoffmann-La Roche.
For more information about Trimeris, Inc., visit the company's website at http://www.trimeris.com.
Trimeris Safe Harbor Statement
Note: Except for any historical information presented herein, matters presented in this release are forward-looking statements that involve risks and uncertainties. The results of Trimeris' previous clinical trials are not necessarily indicative of future clinical trials, and future results could differ materially from past results. For a more detailed description of factors that could cause or contribute to such differences, see Trimeris' filings with the Securities and Exchange Commission.
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Mon Feb 10, 4:30 PM ET
|
By Maggie Fox, Health and Science Correspondent
WASHINGTON (Reuters) - A gel containing
antibodies to the AIDS virus protected female monkeys against infection in an
experiment that suggests such a product might work as an alternative to condoms
for people, researchers reported on Monday.
The study, published in the journal Nature Medicine, helps boost claims by
advocates that an "invisible condom" could be a useful way to help
stop the spread of AIDS, which now infects 36 million people worldwide.
AIDS has no cure and is always fatal, although expensive and toxic drugs can
extend a patient's life for years. Condoms are the best known method for
stopping its transmission.
Half of all new cases of HIV infection are in women, and many who live in
societies where a woman is not always free to demand that her partner use a
condom. In addition many men refuse to use one -- whether having sex with
another man or with a woman.
Thus many experts advocate the development of a gel or cream, akin to
spermicides used for birth control, that men and women alike could use quietly
to prevent infection.
John Moore of Cornell University in New York, Ronald Veazey of Tulane
University in Louisiana and colleagues in the United States and Britain made a
gel using one of the antibodies the human body naturally makes to the HIV virus.
To test it they used monkeys, which do not get AIDS, Researchers have
concocted a substitute virus called SHIV, which is a combination of human
immunodeficiency virus and the monkey version, called SIV.
They put the gel, or a saline solution carrying the antibodies, into the
vaginas of the 12 female monkeys, then put the virus in up to two hours later.
This simulated sexual transmission of the virus.
"Only three of 12 animals ... became infected," they wrote in their
report. In contrast, 12 of 13 animals given a sham treatment became infected
with SHIV.
The antibody Moore's team used does not protect against all strains of HIV,
but it is an important proof of the idea, they said. "These observations
support the concept that viral entry inhibitors can help prevent the sexual
transmission of HIV to humans," they wrote.
Rebekah Webb, policy development officer for the National AIDS Trust in
Britain, welcomed the results.
"It is definitely a step in the right direction but just one of many
promising results from the lab confirming that microbicide is possible,"
she said in a telephone interview.
"One of the huge problems in the microbicide field is funding because no
big pharmaceutical company is interested in microbicide research," Webb
said.
Drug companies have suggested the market is not big enough -- a view that
activists have tried hard to dispel. "We think there is a market. We think
there are many emerging markets around the world and companies should be
interested in that," Webb said.
Many studies have been done on potential microbicides, and some are designed
to prevent infection not only with HIV but with a range or sexually transmitted
diseases, such as syphilis and gonorrhea.
SOURCE: Nature Medicine 2003;10.1038/nm833.
Monday February 10, 3:36 pm ET
"This is a unique opportunity for scientists working in the field to
participate in quality scientific discussion and networking among
colleagues," said. Stephen J. Brown, M.D., ARA's Medical Director.
"We will be able to focus on a number of critical topics including
current barriers to HIV eradication, in vivo and in vitro models of latency,
and the development of potential strategies and therapeutic agents to
eliminate these reservoirs." The HIV reservoirs are formed almost immediately after infection occurs in
human. While many T helper cells are infected, essentially turning them into
factories to make more copies of the virus, some of these cells are infected
and then "go dormant." These dormant cells are activated when the
level of virus in the blood is very low and strong medications are no longer
effective. Essentially, this allows a lifelong pool of HIV for the disease to
rely on even in people on current powerful drugs. Pockets of latently-infected
cells include those in the brain, lymphoid tissue, bone marrow, and genital
tract, among others.
After the advent HAART in 1996, there was great optimism that HIV could be
eradicated in HIV+ people who were being aggressively treated with
combinations of strong drugs that interfered with HIV's ability to reproduce
within cells. However, these hopes relied on the assumptions that the virus
would remain completely suppressed and did not take into account the existence
of the reservoirs, the nature of which was only theorized by some at the time.
The discovery of HIV reservoirs dashed any hopes of a quick cure. It is now
known that HIV can persist for decades within long-lived blood cells. In most
cases observed, if someone stops their HAART medication, the latent HIV begins
producing new viral copies -- flooding the body with millions of new copies
within hours.
However, recent research in the laboratory suggests that certain agents can
"activate" reservoir sites. This in turn has raised hopes among some
researchers that it may one day be possible to "pulse" these
reservoir-activating agents with a new and improved HAART, dealing HIV a
lethal blow by forcing hidden virus into the blood stream where they can then
be killed by existing drugs.
"The very fact that this meeting is happening now is exciting to us.
Very few people held much hope for successfully targeting the reservoirs even
a year ago. There has been a notable change in the minds of many working on
this topic. This workshop offers us some hope that it is not a waste of time
to continue looking for an outright cure," said Irl S. Barefield, ARA's
Executive Director. Barreled notes that the meeting will help AIDS research
Alliance with its own research agenda, as well. AIDS research Alliance is
currently investigating a promising anti-HIV compound called prostratin under
a license from the National Institutes of Health, a unique arrangement between
government and the nonprofit sector to move a drug forward. Prostratin, a drug
derived from a plant native to the Samoan rainforests, has activated each
reservoir site it has been exposed to in the laboratory. Barefield hopes that
human clinical trials of the drug will begin within a year. About AIDS ReSearch Alliance of America
AIDS ReSearch Alliance of America is a non-profit medical research
institution with a mission to find and accelerate the development of effective
treatments for those living with HIV and AIDS. The organization leverages
private funds obtained from industry sponsored clinical research into its own
mission-driven research into novel compounds and approaches for treatment, and
one day the elimination, of HIV-disease. See www.aidsresearch.org for more
information.
About The UCLA Institute of AIDS:
Through research and patient care, the UCLA AIDS Institute seeks to
understand HIV and its pathogenesis, and seeks to use its research for the
practical ends of improving treatments and developing a vaccine for HIV/AIDS.
The Institute is a think tank for collaborating scientists who translate
research breakthroughs into improved treatment.
Press Release
Source: AIDS ReSearch Alliance
AIDS
ReSearch Alliance and UCLA AIDS Institute Convene Meeting Targeting HIV
Reservoirs
Source: AIDS ReSearch Alliance
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Tue Feb 11, 4:31 PM ET
|
By DANIEL Q. HANEY, AP Medical Editor
BOSTON - A variety of highly effective new AIDS drugs are on the horizon, experts say, easing worries that the fast-mutating virus will outstrip doctors' ability to treat it.
Ever since combinations of AIDS medicines transformed HIV into a manageable condition in the mid-1990s, doctors have worried that the virus would eventually mutate into forms that would elude their control. While HIV indeed has evolved into many drug-resistant forms, most patients are still able to find combinations that hold their virus in check.
At the 10th Conference on Retroviruses in Boston, experts said the outlook for potent and novel medicines to control HIV has never been brighter.
"The pipeline of new drugs has an impressive number of candidates in it. This is something we haven't seen in past years. It's a bumper crop," said Dr. John Mellors of the University of Pittsburgh.
Currently, 16 drugs are approved by the Food and Drug Administration to fight AIDS. Most of the medicines are aimed at just two targets in the virus's life cycle, proteins called protease and reverse transcriptate.
However now, doctors say, drugs are in development that are aimed at eight different points in the process by which HIV attaches itself to blood cells, enters them and finally makes new copies of the virus.
The next new drug expected to win FDA approval is T-20, being developed by Roche and Trimeris Inc., a so-called fusion inhibitor that blocks HIV from sticking to the blood cells that it attacks.
At the meeting Tuesday, doctors described encouraging results with the next generation of this drug, called T-1249, that is intended to be used when the virus grows resistant to T-20. Dr. Diego Miralles of Duke University said that even more versions are in the design stage to take over when T-1249 fails.
"I am very encouraged this year that we seem to be keeping up with the virus in terms of our ability to treat resistant virus with new drugs," Mellors said.
At least a half dozen promising drugs are in human testing, he said, and 10 or 12 more are in the pipeline.
Furthermore, AIDS medicines have gotten much easier to take. Just a few years ago, patients had to take 20 or so pills on a carefully timed daily schedule. Now that total is down to just two or three pills taken once or twice a day.
Among the new drugs in testing is one TNX-355, an antibody from Tanox Inc. Unlike other drugs, this one works by blocking the spot on blood cells where HIV normally attaches itself. Initial testing by Dr. Daniel Kuritzkes and others from Brigham and Women's Hospital in Boston found an injection once every one to three weeks dramatically reduced virus levels.
| Press Release | Source: Tanox, Inc. |
Monday February 10, 4:24 pm ET
About Tanox
Tanox, Inc. is a biopharmaceutical company with demonstrated expertise in monoclonal antibody technology. The Company is engaged in the discovery and development of therapeutic monoclonal antibodies designed to address significant unmet medical needs in the areas of asthma, allergy, inflammation and other diseases affecting the human immune system. Xolair(TM), Tanox's most advanced product in development, is an anti-immunoglobulin E, or anti-IgE, antibody whose therapeutic effect has been validated through clinical trials in patients suffering from allergic asthma and seasonal allergic rhinitis (hay fever). Xolair is being developed under an agreement among Tanox, Novartis Pharma AG and Genentech, Inc. In June 2002, Xolair received marketing approval in Australia for treating adults and adolescents with moderate allergic asthma. Genentech submitted an amended Biologics License Application to the FDA in December 2002.
|
Mon Feb 10, 7:35 PM ET
|
Randy Dotinga, Gay.com / PlanetOut.com Network
SUMMARY: A federal study shows that black gay
men, both closeted and out, have significantly higher rates of HIV infection
than other ethnic groups.
New research suggests that young, black gay men are more likely to be
closeted than whites, and African Americans with hidden lives appear to have
much higher HIV infection rates than their counterparts from other races.
According to a federal survey of more than 5,500 young gay and bisexual men
released this month, 14 percent of black men who consider themselves closeted
were found to be HIV-positive. The infection rates were less than half that for
closeted whites and Hispanics.
But even openly gay black men aren't in the clear. Their AIDS infection rates
were even higher -- 24 percent.
The study findings provide more evidence that black men feel more pressure to
live gay lives "on the down low" -- in the closet.
"African-Americans have faced a dilemma: to face the racism within the
(lesbian and gay) community or the homophobia within the African-American
community," said Stephen Thomas, director of the Center for Minority Health
at the University of Pittsburgh, in an interview with HealthScoutNews.com.
The statistics come from interviews between 1994 and 2000 with gay and
bisexual men at bars, nightclubs and other popular gathering spots in six cities
(Baltimore, Dallas, Los Angeles, Miami, New York and Seattle). The men, aged
15-29, were asked to rate their level of "outness" on a scale of one
to seven. They also received HIV and hepatitis B tests.
Researchers considered only 11 percent of all the men surveyed to be closeted
because they said they were only out to a few people. But 18 percent of black
men said they were closeted.
In all ethnic groups, closeted men were much more likely than out men to
consider themselves to be bisexual or even heterosexual.
Among all races, 11 percent of the most closeted men were infected with HIV,
compared to 8 percent of those who were out. Nearly one in four "out"
black men were HIV-positive, compared to 14 percent of those who were closeted.
Black men were also much more likely to be infected with hepatitis B. One in
five "out" black men were infected, and 23 percent of closeted men
were. By comparison, the infection rates for whites and Hispanics ranged from 9
to15 percent.
Thomas, the Center for Minority Health director, told HealthScoutNews.com
that health workers don't know the best ways to reach young, gay black men.
"The truth of this matter is we don't have any concrete, science-based
interventions for this population," he said. "This is the group that's
going to not only get infected themselves but are going to drive infection into
larger populations and large communities, and that should be a concern for
everyone."
Tuesday February 11, 5:00 am ET
Progenics' scientists found that the magnitude of viral load reductions
observed in a previously completed clinical trial were correlated strongly
with viral susceptibility to PRO 542 prior to drug treatment, as measured by
the PhenoSense(TM) HIV Entry assay from ViroLogic, Inc. The Company
believes that viral-resistance testing may identify patients who will derive
the greatest benefit from therapy with HIV entry inhibitors. In addition,
patient viruses collected six weeks after treatment initiation showed no
evidence of having developed resistance to PRO 542. The findings were
presented at the 10th Conference on Retroviruses and Opportunistic Infections
in Boston. PRO 542 belongs to a new class of drugs, viral-entry inhibitors, which are
intended to prevent HIV from entering and infecting cells. Unlike currently
approved therapies that block viral replication in cells already infected with
HIV, PRO 542 is an antibody-like molecule that is designed to target and
neutralize the virus in the bloodstream. Because of its novel mechanism of
action, PRO 542 has the potential to be broadly active against viruses that
have acquired resistance to existing classes of antiretroviral therapies.
Late last year, the Company reported that, in a phase-2 clinical trial,
single doses of PRO 542 reduced concentrations of HIV in the blood by 60% to
80% in a target population of highly treatment-experienced patients. The
viral-load reductions were sustained throughout the six-week follow-up period,
and no serious side effects were observed. Now, new laboratory studies
performed in association with this trial revealed that clinical activity
(cumulative viral-load reduction) was highly correlated (r = 0.97 and p =
0.0077) to in vitro viral susceptibility to PRO 542 as measured via the
PhenoSense HIV Entry assay.
The PhenoSense Entry assay was also used to compare the susceptibility of
patients' viruses to PRO 542 before and after therapy. No significant change
in PRO 542 sensitivity was observed for viruses collected from patients at the
end of the six-week study period, during which time most patients continued to
have reduced viral loads. This clinical finding supports previous laboratory
studies and suggests that viral resistance to PRO 542 does not readily develop
in man.
"We are currently testing PRO 542 in multi-dose phase-2 clinical
studies as therapy for HIV-infected individuals who are no longer responding
to available antiretroviral therapies," explained William C. Olson,
Ph.D., Progenics' Vice President of Research and Development. "The strong
correlation between measurements of viral sensitivity and the magnitude of
viral-load reductions, support the use of the PhenoSense assay in future
clinical studies as a means of identifying and selecting those
treatment-experienced patients who might benefit most from PRO 542
therapy."
Progenics is also developing PRO 140, a second HIV entry inhibitor PRO 140
is a humanized monoclonal antibody that is designed to block HIV entry by
binding to a portion of the CCR5 receptor that the virus uses to infect cells.
PRO 140 has been shown to inhibit the entry of multiple strains of HIV into
immune system cells, in vitro. In addition, it has demonstrated the unique
ability to block HIV entry via CCR5, while leaving the normal function of this
receptor unaffected. Preclinical testing and manufacturing scale-up are
expected to be completed in the coming months, with the Investigational New
Drug Application scheduled to be filed thereafter.
Company Profile
Progenics Pharmaceuticals, Inc. of Tarrytown, NY, is a diversified
biopharmaceutical company focusing on the development and commercialization of
innovative therapeutic products to treat the unmet medical needs of patients
with debilitating conditions and life-threatening diseases. The Company
applies its expertise in immunology and molecular biology to develop
biopharmaceuticals to fight viral diseases, such as human immunodeficiency
virus (HIV) infection, and cancers, including malignant melanoma and prostate
cancer. In supportive care, therapies are being developed to provide patients
with an improved quality of life. Progenics' most clinically advanced product
is methylnaltrexone, a compound in phase-3 clinical testing that is designed
to block the debilitating side effects of opioid analgesics without
interfering with pain palliation. The Company is conducting multi-dose phase-2
clinical trials with its lead HIV product, PRO 542, a viral-entry inhibitor
and is in preclinical development with PRO 140 and other follow-on product
candidates in HIV infection. The Company is developing cancer immunotherapies
based on PSMA (prostate-specific membrane antigen) technology and currently is
conducting phase-1 clinical studies of a therapeutic prostate cancer vaccine.
GMK is a cancer vaccine in phase-3 clinical trials for the treatment of
malignant melanoma.
This press release contains forward-looking statements. Any statements
contained herein that are not statements of historical fact may be
forward-looking statements. When the Company uses the words 'anticipates,'
'plans,' 'expects' and similar expressions they are identifying
forward-looking statements. Such forward-looking statements involve risks and
uncertainties which may cause the Company's actual results, performance or
achievements to be materially different from those expressed or implied by
forward-looking statements. Such factors include, among others, the
uncertainties associated with product development, the risk that clinical
trials will not commence when or proceed as planned, the risks and
uncertainties associated with dependence upon the actions of the Company's
corporate, academic and other collaborators and of government regulatory
agencies, the risk that products that appear promising in early clinical
trials do not demonstrate efficacy in larger-scale clinical trials, the
uncertainty of future profitability and other factors set forth more fully in
the Company's Annual Report on Form 10-K for the fiscal year ended December
31, 2001 and other periodic filings with the Securities and Exchange
Commission to which investors are referred for further information. In
particular, the Company cannot assure you that any of the their programs will
result in a commercial product. The Company does not have a policy of updating
or revising forward-looking statements, and thus it should not be assumed that
the Company's silence over time means that actual events are bearing out as
expressed or implied in such forward-looking statements.
Tuesday February 11, 8:13 am ET
Study 903 is an ongoing three-year, randomized, double-blind trial designed
to compare the efficacy and safety of a treatment regimen of Viread,
lamivudine (3TC) and efavirenz to a regimen of stavudine, lamivudine and
efavirenz in 600 antiretroviral-naive patients with HIV infection. The 96-week
data were presented today (Abstract #564b) at the 10th Conference on
Retroviruses and Opportunistic Infections in Boston, Massachusetts. "These data are impressive because efficacy remains strong in both
arms at 96 weeks, but the Viread-containing arm has a side effect profile that
has continued to improve compared to stavudine since the 48-week point,"
said Schlomo Staszewski, MD, University Hospital, J.W. Goethe-Universitat,
Frankfurt, Germany and a lead investigator for the study. "The potential
for long-term efficacy with reduced side effects compared to stavudine makes
Viread an attractive antiretroviral for use in HIV therapy."
Study Results
The 96-week results presented today show that the Viread and stavudine arms
reduced HIV RNA to less than 400 copies/mL in 82 and 78 percent of patients
respectively, using the most conservative "missing equals failure"
analysis. Seventy-eight and 74 percent of patients achieved HIV RNA less than
50 copies/mL. Excluding missing data, 96 and 93 percent of patients in the
Viread and stavudine arms achieved HIV RNA less than 400 copies/mL and 92 and
88 percent of patients achieved HIV RNA less than 50 copies/mL. Patients in
both arms of the study experienced substantial increases in mean CD4 cell
counts, from the baseline mean of 276 to 537 cells/mm3 in the Viread arm and
from the baseline mean of 283 to 549 cells/mm3 in the stavudine arm. Grade 3
and 4 adverse events and laboratory abnormalities were similar across
treatment groups. Grade 3 and 4 adverse events were reported in less than two
percent of patients and included rash, bacterial infection, depression, fever
and pneumonia. There was a low discontinuation rate of approximately 15
percent in both arms.
Lipid levels (triglycerides and cholesterol) measured in the fasting state
were significantly different between the Viread and stavudine treatment
groups. Patients receiving Viread experienced a mean increase from baseline in
triglycerides of 5 mg/dL, whereas patients in the stavudine group experienced
an increase of 103 mg/dL (p less than 0.001). Increases in low-density
lipoprotein cholesterol (LDL or "bad" cholesterol) were 82 percent
higher for patients receiving stavudine, with an increase of 11 mg/dL in the
Viread arm and an increase of 20 mg/dL in the stavudine arm (p less than
0.001). Significant differences also were noted in the impact of therapy on
high-density lipoprotein cholesterol (HDL or "good" cholesterol),
with patients in the Viread treatment group experiencing a mean increase of 9
mg/dL in "good" cholesterol, compared with an increase of 7 mg/dL in
the stavudine arm (p=0.03). In addition, 10 percent of patients in the
stavudine arm added a lipid-lowering drug during the study compared to two
percent in the Viread arm.
Metabolic Changes
The 96-week data from this study further extend the evidence of Viread's
favorable metabolic profile for treatment-naive patients observed at 48 weeks.
Physician-reported lipodystrophy was observed in one percent of patients
receiving Viread, compared with 12 percent of patients receiving stavudine (p
less than 0.001). In a separate sub-study of 250 patients, whole-body DEXA
scans showed significantly more limb fat in the Viread arm than the stavudine
arm at 96 weeks. Loss of limb fat, or peripheral lipoatrophy, is a crucial
component of lipodystrophy -- characterized as diverse changes in metabolism
and body shape -- which has been associated with long-term administration of
some anti-HIV medications.
Additionally, patients in the Viread arm experienced a favorable weight
gain of 6.1 pounds from baseline versus 0.8 pounds in the stavudine arm
(p=0.002). Weight gain is an important indicator of overall well being for
HIV-infected patients.
Patients who received Viread had significantly fewer adverse events
associated with mitochondrial toxicity, such as peripheral neuropathy, lactic
acidosis and lipodystrophy. After 96 weeks of treatment, the relative risk of
these toxicities was 5.5 fold greater (95 percent confidence interval:
3.0-10.3 fold) in the stavudine-containing arm compared with the Viread-containing
arm.
"These results add to an expanding body of evidence suggesting that
Viread can be broadly effective in suppressing HIV, and also may result in a
lower rate of certain adverse side effects associated with other treatment
regimens," said John C. Martin, PhD, President and Chief Executive
Officer, Gilead Sciences. "As patients and physicians become more aware
and justifiably concerned about the impact of cardiovascular problems and
metabolic conditions such as lipodystrophy, these data support Viread as an
increasingly important treatment option. Avoiding these potentially serious
side effects helps ensure patients will be able to continue to benefit from
therapy for long periods of time."
Study 903 Continues
Gilead designed Study 903 as a three-year trial to gather a wide variety of
data on Viread's efficacy and safety profile in a controlled manner over time.
Study 903 is being conducted in the United States, Europe and South America.
Twenty-six percent of the study participants are women, and 36 percent are
people of color. According to the U.S. Centers for Disease Control, women now
account for 30 percent of new HIV infections in the United States, while
nearly three-fourths of new HIV infections affect non-Caucasians.
About Viread
Viread is the first nucleotide analogue reverse transcriptase inhibitor (NtRTI)
approved for the treatment of HIV in the United States and Europe. Since
approval, approximately 85,000 patients have been prescribed Viread as part of
combination therapy in the United States alone. The U.S. Food and Drug
Administration approved Viread for marketing in October 2001 and the European
Commission granted approval in February 2002. In clinical trials and expanded
access programs, approximately 10,000 patients have been treated with Viread
alone or in combination with other antiretroviral products for periods up to
four years. The drug works by blocking reverse transcriptase, an enzyme
involved in the replication of HIV. The approved dose of Viread for the
treatment of HIV infection is 300 mg once daily taken orally with a meal.
In the United States, Viread is indicated for use in combination with other
antiretroviral agents for the treatment of HIV-1 infection. This indication is
based on analyses of plasma HIV-1 RNA levels and CD4 cell counts in a
controlled study of Viread of 24 weeks duration and in a controlled,
dose-ranging study of Viread of 48 weeks duration. Both studies were conducted
in treatment-experienced adults with evidence of HIV-1 viral replication
despite ongoing antiretroviral therapy. Studies in antiretroviral-naive
patients are ongoing; consequently, the risk-benefit ratio for this population
has yet to be determined.
Safety Profile
Assessment of adverse reactions is based on two studies (902 and 907) in
which 653 treatment-experienced patients received treatment with Viread 300 mg
(n=443) or placebo (n=210) for 24 weeks followed by extended treatment with
the drug. Adverse event rates in the Viread group were similar to those in the
placebo-treated patients. The most common adverse events in these patients
were mild to moderate gastrointestinal events, such as nausea, diarrhea,
vomiting and flatulence. Laboratory abnormalities observed in clinical studies
occurred with similar frequency in the Viread and placebo-treated groups.
In clinical practice, a number of adverse events, including renal
impairment, nausea, rash and asthenia (weakness) have been reported. Renal
impairment occurred most often in patients with underlying systemic or renal
disease, or in patients taking concomitant nephrotoxic agents. Lactic acidosis
and severe hepatomegaly with steatosis, including fatal cases, have been
reported with the use of nucleoside analogues alone or in combination with
other antiretrovirals.
About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and
commercializes therapeutics to advance the care of patients suffering from
life-threatening diseases worldwide. The company has six marketed products and
focuses its research and clinical programs on anti-infectives. Headquartered
in Foster City, CA, Gilead has operations in the United States, Europe and
Australia.
This press release includes forward-looking statements, within the meaning
of the Private Securities Litigation Reform Act of 1995 that are subject to
risks, uncertainties and other factors that could cause actual results to
differ materially from those referred to in the forward-looking statements.
These and other risks are described in detail in the Gilead Annual Report on
Form 10-K for the year ended December 31, 2001 and in Gilead's Quarterly
Reports on Form 10-Q, all of which are on file with the U.S. Securities and
Exchange Commission. All forward-looking statements are based on information
currently available to Gilead and Gilead assumes no obligation to update any
such forward-looking statements.
Tuesday February 11, 8:14 am ET
The ANRS 099 Alize trial is an ongoing three-year, open-label, multicenter
study involving 355 patients who at baseline had to have HIV RNA less than 400
copies/mL while receiving PI-based antiretroviral therapy. The median duration
of PI therapy was 35 months, and the median CD4 cell count was 540 cells/mm3.
Patients were randomized (1:1) to continue their stable PI-based regimen or
switch to an entirely once-daily regimen of emtricitabine, didanosine (another
NRTI) and efavirenz (a non-nucleoside reverse transcriptase inhibitor, or
NNRTI).
"These data suggest that switching to a once-daily, PI-sparing
antiretroviral regimen including emtricitabine is effective in maintaining
suppression of HIV infection," said Dr. Molina. "While both arms of
the study demonstrated comparable and durable antiviral response, the data may
be of particular interest to physicians and patients who now have the
alternative to use a convenient once-daily HAART regimen with a low pill
burden."
Study Results
At 48 weeks, 94 percent of patients receiving the once-daily regimen of
emtricitabine, didanosine and efavirenz had HIV RNA levels (viral load) less
than 400 copies/mL, compared to 92 percent randomized to continue therapy in
the PI-based arm (intent to treat population, assays performed at local
laboratories at investigational centers). When all the samples were analyzed
with a more sensitive assay at a central laboratory, the proportion of
patients with HIV RNA less than 50 copies/mL at week 48 was significantly
higher in the once-daily treatment group. Ninety-five percent of patients in
the once-daily group achieved this result, compared to 87 percent in the
PI-based arm (p=0.01). The median CD4 cell count increase was comparable in
both arms, with an increase of 21 cells/mm3 for patients on the once-daily
regimen and 13 cells/mm3 for those in the PI-based group.
The discontinuation rate in the study was similar between the two arms,
with 10.1 and 12.4 percent of patients in the once-daily arm and PI-based arm
discontinuing, respectively. Additionally, patients switching to once-daily
therapy with emtricitabine, didanosine and efavirenz experienced an increase
of 7.7 mg/dL in fasting high-density lipoprotein cholesterol (HDL - or
"good" cholesterol), as compared to no change in the PI-based arm (p
less than 0.0001). In clinical studies of emtricitabine, the most common
adverse events observed have been infection, diarrhea, headache, nausea and
rash.
"These results suggest that emtricitabine will play a key role in
future anti-HIV therapy, in particular when given with other once-daily
therapies such as Gilead's existing HIV medication, Viread® (tenofovir
disoproxil fumarate)," said John C. Martin, PhD, President and Chief
Executive Officer, Gilead Sciences. "Emtricitabine's ability to control
HIV replication in different treatment combinations confirms our confidence in
this compound. Today's HIV patients and physicians are demanding convenient,
once-daily treatment regimens with minimal side effects. We expect that,
together with Viread, emtricitabine will be important in meeting this
need."
About Emtricitabine
Emtricitabine is a once-daily nucleoside reverse transcriptase inhibitor
currently in Phase III testing for the treatment of HIV and chronic hepatitis
B. Emtricitabine is chemically related to lamivudine (3TC), the most
commonly-prescribed drug for HIV infection. In vitro, the drug has been shown
to be four- to ten-fold more potent than lamivudine.
Applications for marketing approval of emtricitabine for the treatment of
HIV were submitted to U.S. and European regulatory authorities in September
and December of 2002, respectively, by Triangle Pharmaceuticals. Emtricitabine
has not been determined safe or efficacious for the treatment of HIV or
chronic hepatitis B by the FDA or any other regulatory agency.
Press Release
Source: Progenics
Pharmaceuticals, Inc.
Progenics
Presents New Findings from a Phase-2 Clinical Trial of PRO 542 HIV Entry
Inhibitor
Press Release
Source: Gilead Sciences
96-Week
Data From Phase III Study Show Long-Term Efficacy With Reduced Risk of Lipid and
Metabolic Changes for Viread Versus Stavudine in Treatment-Naive HIV Patients
Press Release
Source: Gilead Sciences
Phase
III Data Show Emtricitabine Maintains Viral Load Suppression as Part of
Once-Daily, Protease-Sparing Anti-HIV Regimen