TRIMERIS: Ein Vervielfacher vor dem Ausbruch! - 500 Beiträge pro Seite

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TRIMERIS WKN 910178

Zu Trimeris selbst möchte ich an dieser Stelle nicht viel sagen. Die Story dürfte bekannt sein: es geht um das amerikanische Biotechunternehmen, welches Fuzeon (T-20) mitentwickelt hat, welches Ende letzter Woche die EU-Zulassung bekam.

Der Aktienkurs hat noch nicht vollständig eingepreist, was da wirklich passiert ist! Die neue Medikamentenklasse der Fusionsinhibitoren stellt angesichts der derzeit zunehmenden Resistenzproblematik den einzigen Hoffnungsschimmer bei Millionen mit HIV-1 infizierten dar.

Meldungen des Unternehmens über Probleme bei der Befriedigung der extremen Nachfrage dürften meines Erachtens lediglich ein raffinierter Coup des Unternehmens sein, welches zuvor in die Kritik geraten war, da die Kosten für das Medikament alle bisherigen HIV-Medikamente übertreffen und das Medikament daher primär nur für die Erste Welt gedacht ist.

Das Medikament wird bereits vermarktet, die nächsten Quartalszahlen werden zeigen, dass Trimeris bzgl. der Produktionsprobleme stark übertrieben hatte!


Derzeit nimmt die Aktie an der Nasdaq den Anlauf, die 50 USD-Marke zu knacken, was mit einem zunehmendem Stückvolumen begleitet wird: die Aktie will nach oben durchbrechen und wird dies wohl auch in den nächsten Minuten tun!

Schaut Euch das Ding mal an bzw. schaut mal zu, wie so ein Raketenstart abläuft!

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Contact:

Heather Van Ness
Roche
[phone] Robin Fastenau
Trimeris, Inc.
[phone] Mike Nelson
Manning Selvage & Lee
[phone]

The New England Journal of Medicine Publishes Results of Pivotal Trials Demonstrating Efficacy and Safety of FUZEON™, World`s First FDA-Approved HIV Fusion Inhibitor
Journal Also Highlights Urgent Need for New Classes of HIV Therapies

NUTLEY, N.J. and DURHAM, N.C. (May 28, 2003) — The New England Journal of Medicine today published results from two pivotal studies for FUZEON™ (enfuvirtide), the first in a new class of anti-HIV drugs known as fusion inhibitors. FUZEON, co-developed and co-marketed by Roche and Trimeris, Inc. (Nasdaq: TRMS), was granted accelerated approval on March 13 by the U.S. Food and Drug Administration (FDA), and leads the first new class of anti-HIV therapies to be introduced in seven years. The TORO 1 [T-20 (FUZEON) vs. Optimized Regimen Only] trial was conducted at 48 sites in North and South America, and TORO 2 was conducted at 112 sites in Europe and Australia. Twenty-four week results from the two studies were reported in separate articles in today`s issue of the Journal, along with a review article outlining new and developmental approaches to treating HIV, including FUZEON.

"Response rates seen in the TORO 1 and TORO 2 studies are unprecedented in treatment-experienced patients. Taken together, these results are very positive news for patients who are running out of treatment options," remarked Jacob P. Lalezari, M.D., Director of Quest Clinical Research and Assistant Clinical Professor at the University of California, San Francisco, who is also lead author of the TORO 1 publication. "In both studies, when FUZEON was added to the best available combination of conventional anti-HIV drugs — customized for each patient on the basis of resistance testing and treatment history — those who received FUZEON were twice as likely to achieve undetectable levels of the virus (< 50 copies/mL) than those who took combination therapy without FUZEON. Patients in the FUZEON arm also experienced significantly greater immune system responses."

Unlike other approved anti-HIV drugs, FUZEON blocks HIV`s ability to infect healthy immune (CD4) cells. As a result of its unique mechanism of action, FUZEON is effective in patients with prior exposure to antiretroviral therapy, who may have developed resistance to the other classes of anti-HIV drugs, but as with any anti-HIV drug, patients can also develop resistance to FUZEON.

"The success of current therapy [for HIV] is limited by the emergence of drug resistant viruses, the necessity of sustained adherence to complex regimens, and the potential for toxic effects. Novel classes of safe and effective agents with a low risk of cross-resistance with other antiretroviral drugs are needed," wrote authors J. Michael Kilby, M.D., of the University of Alabama at Birmingham, and Joseph J. Eron, of the University of North Carolina at Chapel Hill, in their article, "Novel Therapies Based on Mechanisms of HIV-1 Cell Entry." Commenting on the FUZEON studies, they noted, "At week 24, the mean reductions in viral load in these patients with relatively advanced and treatment-resistant disease were significantly greater among enfuvirtide recipients than among controls."

"FUZEON provides an important new option for treatment-experienced patients whose current anti-HIV drug regimen is not fully suppressing the virus. Trimeris brought this new therapy to patients together with our partner Roche, and we look forward to further exploring the potential of the fusion inhibitor class," said Dr. Dani Bolognesi, Chief Executive Officer, Trimeris, Inc.

"We are pleased that The New England Journal of Medicine has recognized the relevance of the results from these two trials, which served as the foundation of our submission to the FDA and the basis of their accelerated approval of FUZEON," said Dr. James A. Thommes, Medical Director, Roche.

More About FUZEON

FUZEON in combination with other antiretroviral agents is indicated for the treatment of HIV-1 infection in treatment-experienced patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy. This indication is based on analyses of plasma HIV-1 RNA levels and CD4 cell counts in controlled studies of FUZEON of 24 weeks` duration. Subjects enrolled were treatment-experienced adults; many had advanced disease. There are no studies of FUZEON in antiretroviral naive patients. There are no results from controlled trials evaluating the effect of FUZEON on clinical progression of HIV-1.

FUZEON 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 at 24 weeks had at least one local injection site reaction. Manifestations of injection site reactions may include pain and discomfort, induration, erythema, nodules and cysts, pruritus, and ecchymosis.

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. The events most frequently reported in subjects receiving FUZEON plus an individualized regimen were diarrhea (26.8%), nausea (20.1%), and fatigue (16.1%). All these events were seen at a lower incidence than in subjects that received background regimen alone: diarrhea (33.5%), nausea (23.7%), and fatigue (17.4%). The most common adverse events seen more frequently in patients receiving FUZEON plus an individualized regimen than in patients who received treatment without FUZEON include headache (11.8%), peripheral neuropathy (8.9%), dizziness (6.6%), insomnia (11.3%), depression (8.6%), decreased appetite (6.3%), asthenia (5.7%), myalgia (5.0%), constipation (3.9%) and pancreatitis (2.4%). The majority of adverse events were of mild or moderate intensity. Hypersensitivity reactions have been associated with FUZEON therapy (less than or equal to 1 percent) and have recurred on rechallenge. Symptoms of an allergic reaction may include rash, fever, nausea and vomiting, chills, rigors, hypotension, and elevated serum transaminases. In addition, an increased rate of bacterial pneumonia was observed in patients treated with FUZEON in the Phase III clinical trials compared to the control arm. It is unclear if the increased incidence of pneumonia is related to FUZEON use. The list of side effects is not complete at this time because FUZEON is still being studied.

FUZEON does not cure HIV infection or AIDS. Patients taking FUZEON may acquire opportunistic infections or other conditions that are associated with HIV infection. FUZEON does not reduce the risk of transmission of HIV to others through sexual contact or blood contamination. Patients should continue to practice safer sex by using latex or polyurethane condoms or other barrier methods. Never use or share dirty needles.

Additional information on FUZEON is available at www.FUZEON.com or by calling 1-877-4-FUZEON.

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Fact Sheet: FUZEON™ Studies Published in The New England Journal of Medicine


Study Design of TORO 1 and TORO 2
TORO 1 and TORO 2 are randomized, open-label trials that enrolled approximately 1,000 HIV-1 infected patients at 112 centers internationally. TORO 1, the first Phase III trial, conducted in North America and Brazil, enrolled 491 patients who had previously been treated with an average of 12 antiretrovirals. The median baseline viral load was 5.2 log10 copies/mL and median CD4+ count was 80 cells/mm3. TORO 2, the second Phase III clinical trial, conducted in Europe and Australia, enrolled 504 patients who had previously been treated with an average of 11 antiretrovirals. The median baseline viral load was 5.1 log10 copies/mL and median CD4+ count was 98 cells/mm3. Ninety percent of patients had virus with five or more primary mutations to the three existing antiretroviral classes.

At entry for TORO 1 and TORO 2, resistance testing and patient treatment history were used together to aid in the selection of an individualized regimen of three to five anti-HIV drugs for each patient. After selection of the regimen, patients were randomized 2:1 to receive either the individualized regimen in combination with FUZEON™ (enfuvirtide) or the individualized regimen alone. Study protocol allowed for inclusion of investigational and newly approved therapies, tenofovir and lopinavir/ritonavir, in the background regimen. Patients who met virologic failure at study defined intervals beginning at week eight in either the FUZEON or control arms were permitted to modify their regimens. Patients receiving FUZEON could choose to continue to receive FUZEON, and patients in the control group were permitted to add FUZEON as well as modify the therapies in their background regimens.

TORO 1 Results at 24 Weeks

In TORO 1, 37 percent of patients who were treated with FUZEON in combination with an optimized background regimen had undetectable blood levels (less than 400 copies/mL) of HIV at 24 weeks, compared to 16 percent who received an optimized background regimen alone (p<0.0001). Combination therapy with FUZEON further reduced HIV viral load to less than 50 copies/mL in 20 percent of patients as compared to 7 percent who took combination therapy alone (P=0.0002).

The primary efficacy endpoint for the study, the mean difference in the magnitude of decrease in HIV between the two groups in the study, was 0.934 log10 copies/mL (<0.0001). Patients who received FUZEON as part of their combination regimen achieved a reduction in HIV levels of 1.697 log10 copies/mL, compared to 0.763 log10 copies/mL for those in the control arm. Furthermore, 52 percent of patients receiving FUZEON experienced a 1.0 log10 or greater reduction in HIV levels, compared to 29 percent who did not receive FUZEON (<0.0001). Patients in the FUZEON arm experienced a mean CD4+ cell increase of 76 cells/mm3, as compared to 32 cells/mm3 in the control arm (<0.0001).

TORO 2 Results at 24 Weeks

Results from TORO 2 were consistent with findings from TORO 1. In TORO 2, 28 percent of patients who were treated with FUZEON in combination with an optimized background regimen had undetectable blood levels (less than 400 copies/mL) of HIV at 24 weeks, compared to 14 percent receiving an optimized background regimen alone (<0.0001). Combination therapy with FUZEON further reduced HIV viral load to less than 50 copies/mL in 12 percent of patients as compared to 5 percent who took combination therapy alone (P=0.0099).

The mean difference in the magnitude of decrease in HIV between the two arms at 24 weeks was 0.78 log10 copies/mL (<0.0001). Patients who received FUZEON as part of their combination regimen achieved a mean reduction in HIV levels of 1.43 log10 copies/mL, compared to a mean of 0.65 log10 copies/mL for those in control arm. Furthermore, 43 percent of patients receiving FUZEON experienced a 1.0 log10 or greater reduction in HIV levels, compared to 21 percent who did not receive FUZEON (<0.0001). Patients in the FUZEON arm experienced a mean CD4+ cell increase of 65 cells/mm3, as compared to 38 cells/mm3 in the control arm (p=0.023).

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 (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 and diagnostics. 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 website at: www.rocheusa.com.

About Trimeris, Inc.
Trimeris, Inc. (Nasdaq: TRMS) is a biopharmaceutical company engaged in the discovery, development and commercialization of novel therapeutic agents for the treatment of viral disease. The core technology platform of fusion inhibition is based on blocking viral entry into host cells. FUZEON, recently approved in the U.S. and European Union, is the first in a new class of anti-HIV drugs called fusion inhibitors. 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 Ltd. For more information about Trimeris, please visit the company`s website at www.trimeris.com.

Trimeris Safe Harbor Statement
Note: This document and any attachments may contain forward-looking information about the Company`s financial results and business prospects that involve substantial risks and uncertainties. These statements can be identified by the fact that they use words such as "expect," "project," "intend," "plan," "believe" and other words and terms of similar meaning. Among the factors that could cause actual results to differ materially are the following: there is uncertainty regarding the success of research and development activities, regulatory authorizations and product commercializations; the results of our previous clinical trials are not necessarily indicative of future clinical trials; and our drug candidates are based upon novel technology, are difficult and expensive to manufacture and may cause unexpected side effects. For a detailed description of these factors, see Trimeris` Form 10-K filed with the Securities and Exchange Commission on March 27, 2003 and its periodic reports filed with the SEC.

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[benefactor [KommA]]

TRMS

Revenues (Units in Thousands of U.S. Dollars $)

Quarter 2002 2003

Q1 326 236
Q2 326 --
Q3 326 --
Q4 155 --

Earnings Per Share (Units in U.S. Dollars $)

Quarter 2002 2003

Q1 -0.97 -0.75
Q2 -0.89 --
Q3 -0.97 --
Q4 -1.09 --

Total -3.92 -0.75

Market Cap 1054.36 Mio.

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Contact:

Heather Van Ness
Roche
[phone] Robin Fastenau
Trimeris, Inc.
[phone] Mike Nelson
Manning Selvage & Lee
[phone]

European Commission Approves FUZEON™, First HIV Fusion Inhibitor, For Use Against HIV in the European Union

NUTLEY, N.J. and DURHAM, N.C. (May 27, 2003) — Roche and Trimeris, Inc. (Nasdaq: TRMS) announced today that the European Commission has approved FUZEON™ (enfuvirtide) for use in the European Union (EU). The EU action enables use of FUZEON in all 15 member countries and represents the third regulatory approval for FUZEON, following regulatory clearance in the U.S. and Switzerland. It is expected that the market introduction of FUZEON will occur over the next several months on a county-specific basis.

FUZEON is the first fusion inhibitor, representing the first new class of anti-HIV treatments in seven years. Unlike other anti-HIV drugs which work once HIV has already entered the human immune (CD4) cell, FUZEON blocks HIV`s ability to infect immune cells in the first place. When used with other anti-HIV medicines, FUZEON can reduce the amount of HIV in the blood, which leads to an increase in the number of CD4 cells. There are no results from controlled trials evaluating the effect of FUZEON on clinical progression of HIV-1.

The indication for FUZEON in the European Union is for "use in combination with other antiretroviral medicinal products for the treatment of HIV-1 infected patients who have received treatment with and failed on regimens containing at least one medicinal product from each of the following antiretroviral classes, protease inhibitors, non-nucleoside reverse transcriptase inhibitors and nucleoside reverse transcriptase inhibitors, or who have intolerance to previous antiretroviral regimens. In deciding on a new regimen for patients who have failed an antiretroviral regimen, careful consideration should be given to the treatment history of the individual patient and the patterns of mutations associated with different medicinal products. Where available, resistance testing may be appropriate."

"The approval of FUZEON by the European Medicines Evaluation Agency today represents an important advance in the fight against HIV, bringing with it new hope for treatment-experienced people living with HIV in Europe," said Bill Burns, Head of Pharmaceuticals, Roche.

"Today`s announcement of the European approval is excellent news," said Dr. Dani Bolognesi, CEO of Trimeris, Inc. "The rapid European approval reflects the efficacy and safety of FUZEON shown in the two pivotal phase III studies, as well as the compelling need for this new therapy."

For more information about Fuzeon, visit www.fuzeon.com

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Facts About FUZEON™ (enfuvirtide)


About FUZEON
FUZEON is the first new class of anti-HIV drugs in seven years. Unlike other HIV drugs that work after HIV has entered the human immune cell, FUZEON works outside of the CD4 cell, blocking HIV from entering the cell. Patients may still develop resistance to FUZEON.

FUZEON in combination with other antiretroviral agents is indicated for the treatment of HIV-1 infection in treatment-experienced patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy. This indication is based on analyses of plasma HIV-1 RNA levels and CD4 cell counts in controlled studies of FUZEON of 24 weeks` duration. Subjects enrolled were treatment-experienced adults; many had advanced disease. There are no studies of FUZEON in antiretroviral naive patients. There are no results from controlled trials evaluating the effect of FUZEON on clinical progression of HIV-1.

FUZEON 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 at 24 weeks had at least one local injection site reaction. Manifestations of injection site reactions may include pain and discomfort, induration, erythema, nodules and cysts, pruritus, and ecchymosis.

There was less than five percent difference in the most common adverse events seen between FUZEON plus an individualized regimen of antiretroviral drugs and an individualized regimen alone. The events most frequently reported in subjects receiving FUZEON plus an individualized regimen were diarrhea (26.8%), nausea (20.1%), and fatigue (16.1%). All these events were seen at a lower incidence than in subjects that received background regimen alone: diarrhea (33.5%), nausea (23.7%), and fatigue (17.4%). The most common adverse events seen more frequently in patients receiving FUZEON plus an individualized regimen than in patients who received treatment without FUZEON include headache (11.8%), peripheral neuropathy (8.9%), dizziness (6.6%), insomnia (11.3%), depression (8.6%), decreased appetite (6.3%), asthenia (5.7%), myalgia (5.0%), constipation (3.9%) and pancreatitis (2.4%). The majority of adverse events were of mild or moderate intensity. Hypersensitivity reactions have been associated with FUZEON therapy (less than or equal to 1 percent) and have recurred on rechallenge. Symptoms of an allergic reaction may include rash, fever, nausea and vomiting, chills, rigors, hypotension, and elevated serum transaminases. In addition, an increased rate of bacterial pneumonia was observed in patients treated with FUZEON in the Phase III clinical trials compared to the control arm. It is unclear if the increased incidence of pneumonia is related to FUZEON use. The list of side effects is not complete at this time because FUZEON is still being studied.

FUZEON does not cure HIV infection or AIDS. Patients taking FUZEON may acquire opportunistic infections or other conditions that are associated with HIV infection. FUZEON does not reduce the risk of transmission of HIV to others through sexual contact or blood contamination. Patients should continue to practice safer sex by using latex or polyurethane condoms or other barrier methods. Never use or share dirty needles.

For more information about FUZEON, visit www.fuzeon.com

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 (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 and diagnostics. 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 website at: http://www.rocheusa.com.

About Trimeris, Inc.
Trimeris, Inc. (Nasdaq: TRMS) is a biopharmaceutical company engaged in the discovery, development and commercialization of novel therapeutic agents for the treatment of viral disease. The core technology platform of fusion inhibition is based on blocking viral entry into host cells. FUZEON, recently approved in the U.S. and the European Union, is the first in a new class of anti-HIV drugs called fusion inhibitors. 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 Ltd. For more information about Trimeris, please visit the company`s website at www.trimeris.com.

Trimeris Safe Harbor Statement
Note: This document and any attachments may contain forward-looking information about the Company`s financial results and business prospects that involve substantial risks and uncertainties. These statements can be identified by the fact that they use words such as "expect," "project," "intend," "plan," "believe" and other words and terms of similar meaning. Among the factors that could cause actual results to differ materially are the following: there is uncertainty regarding the success of research and development activities, regulatory authorizations and product commercializations; the results of our previous clinical trials are not necessarily indicative of future clinical trials; and our drug candidates are based upon novel technology, are difficult and expensive to manufacture and may cause unexpected side effects. For a detailed description of these factors, see Trimeris` Form 10-K filed with the Securities and Exchange Commission on March 27, 2003 and its periodic reports filed with the SEC.

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Mittwoch, 28. Mai 2003 | 10:40 Uhr [Artikel versenden] [Artikel drucken] [zurück]

Roche erhält EU-Zulassung für HIV-Medikament Fuzeon
Der Basler Pharmakonzern Roche Holding AG erhielt von der EU-Kommission die Marktzulassung für sein Arzneimittel Fuzeon zur Behandlung einer Infektion mit HIV-1. Vergangene Woche genehmigte die Schweiz als erstes europäisches Land den Vertrieb des HIV-Medikaments.

Die EU-Zulassung von Fuzeon erfolgt, nachdem das Medikament im März bereits in den USA wurde. In Australien und Kanada wurde die Zulassung des Medikaments beantrag, jedoch hben die Behörden ihre Prüfungen noch nicht abgeschlossen.

Roche und sein US-Entwicklungspartner Trimeris Inc. gerieten kürzlich in Zusammenhang mit Fuzeon, das auch als T-20 bekannt ist, in die Kritik. Zum einen können die Partner vermutlich kaum die Nachfrage in den Industrieländern befriedigen, zum anderen fordern sie einen Rekordpreis von jährlich über 20.000 Dollar.

Der Wirkstoff ist aufwändig herzustellen und zählt zu einer neuen Klasse von HIV-Medikamenten, den Fusionshemmern, die verhindern, dass der Virus in die gesunde menschliche Immunzelle eindringt. Sämtliche bisher verfügbaren Medikamente attackieren den Virus erst, nachdem die Zellen befallen sind. Deshalb wirkt Fuzeon auch bei Patienten, die eine Resistenz gegen andere HIV/AIDS-Medikamente entwickelt haben. Roche rechnet mit jährlichen Peak-Sales von bis zu 1,0 Mrd. CHF.

Die Genussscheine von Roche stiegen bisher um 1,78 Prozent und notieren aktuell bei 97,25 CHF.

Wertpapiere des Artikels:
TRIMERIS INC. DL-,001
ROCHE HLDG AG GEN.



Autor: , 10:40 28.05.03

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Was geht ab? Wann bricht das Dreieck endlich nach oben aus?


Geld(bid) Brief(ask) Umsatz Kurs Zeit
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Naja, hat dann doch alles so geklappt, wie ich mir das vorgestellt hatte - allerdings mit ein paar Stunden Verzögerung

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Anti-HIV-1 activity of enfuvirtide (T-20) by inhibition of bystander cell death [In Process Citation]
Antivir Ther 2003 Apr;8(2):155-61 (ISSN: 1359-6535)
Barretina J; Blanco J; Armand-Ugon M; Gutierrez A; Clotet B; Este JA
Retrovirology Laboratory irsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autonoma de Barcelona, 08916 Badalona, Spain.
Infection by human immunodeficiency virus type 1 (HIV-1) has been associated with increased cell death of both infected and bystander cells. The envelope glycoprotein complex appears to play an active role in HIV-induced death of bystander cells. We quantified cell-to-cell fusion, single cell death and membrane lipid mixing in cocultures of effector, HIV-1 envelope-expressing cells with peripheral blood mononuclear cells or purified CD4 T lymphocytes from HIV-negative donors, in the presence or the absence of the fusion inhibitor enfuvirtide (T-20, pentafuside, Fuzeon). T-20, which blocks gp41-dependent virus-cell fusion, showed a complete and dose-dependent inhibition of syncytium formation in cocultures of envelope-expressing cells with uninfected cells. Similarly, T-20 totally abrogated death of single bystander CD4 T cells with an IC50 of 0.04 microg/ml. Membrane lipid mixing, as a measure of interaction between envelope-expressing cells and CD4 cells, was also dose-dependently inhibited by T-20. Moreover, effector cells chronically infected with a T-20-resistant virus recovered the ability to induce bystander cell death in the presence of the drug, supporting the role of gp41 in single cell death. In conclusion, T-20 is able to protect CD4 T cells from envelope presentation with a dual effect: inhibition of virus replication and blockade of HIV-1 envelope-induced cell death of bystander CD4 T cells. Protection of cells prior to infection from HIV envelope-dependent bystander effect could lead to a better immune restoration of HIV-1-infected patients that are treated with T-20.
Language: English
MEDLINE Indexing Date: 200305
Publication Type: Owner: NLM; Status: In-Process
Publication Type: Journal Article
PMID: 0012741628
Unique NLM Identifier: 22626460
Journal Code: IM

Quelle: http://www.medline.de/

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The New England Journal of Medicine Publishes Results of Pivotal Trials Demonstrating Efficacy and Safety of FUZEON™, World`s First FDA-Approved HIV Fusion Inhibitor
Journal Also Highlights Urgent Need for New Classes of HIV Therapies

NUTLEY, N.J. and DURHAM, N.C. (May 28, 2003) — The New England Journal of Medicine today published results from two pivotal studies for FUZEON™ (enfuvirtide), the first in a new class of anti-HIV drugs known as fusion inhibitors. FUZEON, co-developed and co-marketed by Roche and Trimeris, Inc. (Nasdaq: TRMS), was granted accelerated approval on March 13 by the U.S. Food and Drug Administration (FDA), and leads the first new class of anti-HIV therapies to be introduced in seven years. The TORO 1 [T-20 (FUZEON) vs. Optimized Regimen Only] trial was conducted at 48 sites in North and South America, and TORO 2 was conducted at 112 sites in Europe and Australia. Twenty-four week results from the two studies were reported in separate articles in today`s issue of the Journal, along with a review article outlining new and developmental approaches to treating HIV, including FUZEON.

"Response rates seen in the TORO 1 and TORO 2 studies are unprecedented in treatment-experienced patients. Taken together, these results are very positive news for patients who are running out of treatment options," remarked Jacob P. Lalezari, M.D., Director of Quest Clinical Research and Assistant Clinical Professor at the University of California, San Francisco, who is also lead author of the TORO 1 publication. "In both studies, when FUZEON was added to the best available combination of conventional anti-HIV drugs — customized for each patient on the basis of resistance testing and treatment history — those who received FUZEON were twice as likely to achieve undetectable levels of the virus (< 50 copies/mL) than those who took combination therapy without FUZEON. Patients in the FUZEON arm also experienced significantly greater immune system responses."

Unlike other approved anti-HIV drugs, FUZEON blocks HIV`s ability to infect healthy immune (CD4) cells. As a result of its unique mechanism of action, FUZEON is effective in patients with prior exposure to antiretroviral therapy, who may have developed resistance to the other classes of anti-HIV drugs, but as with any anti-HIV drug, patients can also develop resistance to FUZEON.

"The success of current therapy [for HIV] is limited by the emergence of drug resistant viruses, the necessity of sustained adherence to complex regimens, and the potential for toxic effects. Novel classes of safe and effective agents with a low risk of cross-resistance with other antiretroviral drugs are needed," wrote authors J. Michael Kilby, M.D., of the University of Alabama at Birmingham, and Joseph J. Eron, of the University of North Carolina at Chapel Hill, in their article, "Novel Therapies Based on Mechanisms of HIV-1 Cell Entry." Commenting on the FUZEON studies, they noted, "At week 24, the mean reductions in viral load in these patients with relatively advanced and treatment-resistant disease were significantly greater among enfuvirtide recipients than among controls."

"FUZEON provides an important new option for treatment-experienced patients whose current anti-HIV drug regimen is not fully suppressing the virus. Trimeris brought this new therapy to patients together with our partner Roche, and we look forward to further exploring the potential of the fusion inhibitor class," said Dr. Dani Bolognesi, Chief Executive Officer, Trimeris, Inc.

"We are pleased that The New England Journal of Medicine has recognized the relevance of the results from these two trials, which served as the foundation of our submission to the FDA and the basis of their accelerated approval of FUZEON," said Dr. James A. Thommes, Medical Director, Roche.

More About FUZEON

FUZEON in combination with other antiretroviral agents is indicated for the treatment of HIV-1 infection in treatment-experienced patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy. This indication is based on analyses of plasma HIV-1 RNA levels and CD4 cell counts in controlled studies of FUZEON of 24 weeks` duration. Subjects enrolled were treatment-experienced adults; many had advanced disease. There are no studies of FUZEON in antiretroviral naive patients. There are no results from controlled trials evaluating the effect of FUZEON on clinical progression of HIV-1.

FUZEON 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 at 24 weeks had at least one local injection site reaction. Manifestations of injection site reactions may include pain and discomfort, induration, erythema, nodules and cysts, pruritus, and ecchymosis.

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. The events most frequently reported in subjects receiving FUZEON plus an individualized regimen were diarrhea (26.8%), nausea (20.1%), and fatigue (16.1%). All these events were seen at a lower incidence than in subjects that received background regimen alone: diarrhea (33.5%), nausea (23.7%), and fatigue (17.4%). The most common adverse events seen more frequently in patients receiving FUZEON plus an individualized regimen than in patients who received treatment without FUZEON include headache (11.8%), peripheral neuropathy (8.9%), dizziness (6.6%), insomnia (11.3%), depression (8.6%), decreased appetite (6.3%), asthenia (5.7%), myalgia (5.0%), constipation (3.9%) and pancreatitis (2.4%). The majority of adverse events were of mild or moderate intensity. Hypersensitivity reactions have been associated with FUZEON therapy (less than or equal to 1 percent) and have recurred on rechallenge. Symptoms of an allergic reaction may include rash, fever, nausea and vomiting, chills, rigors, hypotension, and elevated serum transaminases. In addition, an increased rate of bacterial pneumonia was observed in patients treated with FUZEON in the Phase III clinical trials compared to the control arm. It is unclear if the increased incidence of pneumonia is related to FUZEON use. The list of side effects is not complete at this time because FUZEON is still being studied.

FUZEON does not cure HIV infection or AIDS. Patients taking FUZEON may acquire opportunistic infections or other conditions that are associated with HIV infection. FUZEON does not reduce the risk of transmission of HIV to others through sexual contact or blood contamination. Patients should continue to practice safer sex by using latex or polyurethane condoms or other barrier methods. Never use or share dirty needles.

Additional information on FUZEON is available at www.FUZEON.com or by calling 1-877-4-FUZEON.

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Fact Sheet: FUZEON™ Studies Published in The New England Journal of Medicine


Study Design of TORO 1 and TORO 2
TORO 1 and TORO 2 are randomized, open-label trials that enrolled approximately 1,000 HIV-1 infected patients at 112 centers internationally. TORO 1, the first Phase III trial, conducted in North America and Brazil, enrolled 491 patients who had previously been treated with an average of 12 antiretrovirals. The median baseline viral load was 5.2 log10 copies/mL and median CD4+ count was 80 cells/mm3. TORO 2, the second Phase III clinical trial, conducted in Europe and Australia, enrolled 504 patients who had previously been treated with an average of 11 antiretrovirals. The median baseline viral load was 5.1 log10 copies/mL and median CD4+ count was 98 cells/mm3. Ninety percent of patients had virus with five or more primary mutations to the three existing antiretroviral classes.

At entry for TORO 1 and TORO 2, resistance testing and patient treatment history were used together to aid in the selection of an individualized regimen of three to five anti-HIV drugs for each patient. After selection of the regimen, patients were randomized 2:1 to receive either the individualized regimen in combination with FUZEON™ (enfuvirtide) or the individualized regimen alone. Study protocol allowed for inclusion of investigational and newly approved therapies, tenofovir and lopinavir/ritonavir, in the background regimen. Patients who met virologic failure at study defined intervals beginning at week eight in either the FUZEON or control arms were permitted to modify their regimens. Patients receiving FUZEON could choose to continue to receive FUZEON, and patients in the control group were permitted to add FUZEON as well as modify the therapies in their background regimens.

TORO 1 Results at 24 Weeks

In TORO 1, 37 percent of patients who were treated with FUZEON in combination with an optimized background regimen had undetectable blood levels (less than 400 copies/mL) of HIV at 24 weeks, compared to 16 percent who received an optimized background regimen alone (p<0.0001). Combination therapy with FUZEON further reduced HIV viral load to less than 50 copies/mL in 20 percent of patients as compared to 7 percent who took combination therapy alone (P=0.0002).

The primary efficacy endpoint for the study, the mean difference in the magnitude of decrease in HIV between the two groups in the study, was 0.934 log10 copies/mL (<0.0001). Patients who received FUZEON as part of their combination regimen achieved a reduction in HIV levels of 1.697 log10 copies/mL, compared to 0.763 log10 copies/mL for those in the control arm. Furthermore, 52 percent of patients receiving FUZEON experienced a 1.0 log10 or greater reduction in HIV levels, compared to 29 percent who did not receive FUZEON (<0.0001). Patients in the FUZEON arm experienced a mean CD4+ cell increase of 76 cells/mm3, as compared to 32 cells/mm3 in the control arm (<0.0001).

TORO 2 Results at 24 Weeks

Results from TORO 2 were consistent with findings from TORO 1. In TORO 2, 28 percent of patients who were treated with FUZEON in combination with an optimized background regimen had undetectable blood levels (less than 400 copies/mL) of HIV at 24 weeks, compared to 14 percent receiving an optimized background regimen alone (<0.0001). Combination therapy with FUZEON further reduced HIV viral load to less than 50 copies/mL in 12 percent of patients as compared to 5 percent who took combination therapy alone (P=0.0099).

The mean difference in the magnitude of decrease in HIV between the two arms at 24 weeks was 0.78 log10 copies/mL (<0.0001). Patients who received FUZEON as part of their combination regimen achieved a mean reduction in HIV levels of 1.43 log10 copies/mL, compared to a mean of 0.65 log10 copies/mL for those in control arm. Furthermore, 43 percent of patients receiving FUZEON experienced a 1.0 log10 or greater reduction in HIV levels, compared to 21 percent who did not receive FUZEON (<0.0001). Patients in the FUZEON arm experienced a mean CD4+ cell increase of 65 cells/mm3, as compared to 38 cells/mm3 in the control arm (p=0.023).

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 (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 and diagnostics. 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 website at: www.rocheusa.com.

About Trimeris, Inc.
Trimeris, Inc. (Nasdaq: TRMS) is a biopharmaceutical company engaged in the discovery, development and commercialization of novel therapeutic agents for the treatment of viral disease. The core technology platform of fusion inhibition is based on blocking viral entry into host cells. FUZEON, recently approved in the U.S. and European Union, is the first in a new class of anti-HIV drugs called fusion inhibitors. 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 Ltd. For more information about Trimeris, please visit the company`s website at www.trimeris.com.

Trimeris Safe Harbor Statement
Note: This document and any attachments may contain forward-looking information about the Company`s financial results and business prospects that involve substantial risks and uncertainties. These statements can be identified by the fact that they use words such as "expect," "project," "intend," "plan," "believe" and other words and terms of similar meaning. Among the factors that could cause actual results to differ materially are the following: there is uncertainty regarding the success of research and development activities, regulatory authorizations and product commercializations; the results of our previous clinical trials are not necessarily indicative of future clinical trials; and our drug candidates are based upon novel technology, are difficult and expensive to manufacture and may cause unexpected side effects. For a detailed description of these factors, see Trimeris` Form 10-K filed with the Securities and Exchange Commission on March 27, 2003 and its periodic reports filed with the SEC.

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New Data Show FUZEON-Based Regimens Deliver Superior, Sustained Response In Treatment-Experienced Patients
7/15/03





PARIS, Jul 15, 2003 /PRNewswire-FirstCall via COMTEX/ --
New data from Phase III studies of FUZEON(TM) (enfuvirtide), the first and only approved fusion inhibitor for the treatment of HIV, demonstrate that two-thirds of treatment-experienced patients who began combination therapy with FUZEON achieved undetectable levels of HIV (less than 400 copies/mL) when they began therapy with less advanced disease and after prior exposure to fewer anti-HIV drugs. FUZEON-based regimens provided superior virologic and immunologic responses compared to an individualized combination of anti-HIV drugs without FUZEON. A superior response was also seen in patients with few or no other remaining treatment options, 21 percent of whom achieved undetectable levels of HIV on a FUZEON-based regimen. These data were presented today in an oral session by Dr. Julio Montaner at the 2nd International AIDS Society (IAS) Conference on HIV Pathogenesis and Treatment, being held in Paris, July 13-16.

The data (abstract 116), derived from a new detailed sub-analysis of the combined FUZEON Phase III studies, show that 68 percent of patients who began a FUZEON-based regimen with less advanced disease (CD4 cell count of greater than 100 cells/mm3) and less treatment experience (six to 10 prior anti-HIV drugs) achieved undetectable levels of HIV (less than 400 copies/mL) at 24 weeks, compared to 39 percent of patients who were treated with an optimized combination of anti-HIV drugs without FUZEON. In patients with the most advanced disease (CD4 cell count less than 100 cells/mm3) and treatment experience (greater than 10 prior anti-HIV drugs), 23 percent of those receiving FUZEON-based regimens were still able to achieve less than 400 copies/mL of HIV at 24 weeks, compared to five percent for patients who did not have FUZEON in their regimen. These results were statistically significant (p<0.05).

The superiority of FUZEON-based regimens versus the control arm at 24 weeks was observed across all patient subgroups, categorized by the number of active agents in the background regimen. Further analysis also demonstrated that FUZEON plus one active drug reduced HIV to undetectable levels in a similar or greater proportion of patients (35 percent) than combinations of three, four or five active drugs without FUZEON (38 percent, 26 percent and 20 percent, respectively).

`These data are most noteworthy because treatment-experienced patients have historically shown poor response rates compared to patients who initiate HIV therapy for the first time,`said Julio Montaner, M.D., Chair of AIDS Research, St. Paul`s Hospital, University of British Columbia, Vancouver. `This analysis of the TORO studies provides evidence that initiating combination therapy with FUZEON in treatment-experienced patients with less advanced disease and less prior exposure to anti-HIV drugs can allow substantial numbers of these patients to achieve undetectable levels of HIV.` Montaner further indicated, `FUZEON provided important improvements in viral load reduction and immunologic response in patients with few or no active drugs available.`

A separate, related oral presentation (abstract LB02) in the late-breaker session at IAS will show that almost all patients who achieved undetectable levels of HIV (less than 400 copies/mL) at 24 weeks maintained this response at 48 weeks, confirming the durability of FUZEON-based regimens in treatment-experienced patients.

At 48 weeks, patients who added FUZEON to an individualized combination of other anti-HIV drugs were more than twice as likely to achieve undetectable levels of HIV (less than 400 copies/mL) compared to patients who received combination therapy without FUZEON (30 percent vs. 12 percent). This parallels the 24-week results, where 33 percent of patients in the FUZEON arm and 15 percent of patients in the control arm, respectively, had undetectable levels of HIV. FUZEON-based combinations also delivered a 100 percent greater increase in the number of immune (CD4) cells at 48 weeks compared to the individualized combination (increase of 91 cells/mm3 in the FUZEON arm vs. 45 cells/mm3 in the control arm). This was an improvement in immune status compared to 24 weeks, when patients in the FUZEON arm saw an increase of 71 cells/mm3, compared to 35 cells/mm3 in the control arm. In addition, the mean duration of viral suppression was three times longer for patients receiving FUZEON-based regimens than for those receiving regimens without FUZEON (32 weeks vs. 11 weeks). All of these results were highly statistically significant (p<0.0001).

The superiority of FUZEON-based regimens versus the control arm at 48 weeks was observed across all patient subgroups, categorized by the number of active agents in the background regimen. Among patients whose virus was sensitive to one drug in the background regimen, 29 percent of patients in the FUZEON arm achieved undetectable levels of HIV, compared to seven percent in the control arm. A greater number of patients who had at least two active agents in their background regimen achieved undetectable HIV in the FUZEON arm at 48 weeks compared to the control arm (38 percent vs. 18 percent). All of these results were statistically significant (p<0.05).

`In FUZEON, we have the first agent which targets the virus before it enters an immune cell. This new fusion inhibitor has now been shown to have a durable effect for almost a year in treatment-experienced patients,`said Calvin J. Cohen, M.D., Director, Community Research Initiative of New England, Boston. `Patients on a FUZEON-based regimen continued to experience a significantly greater virologic and immunologic benefit when compared to patients who received a regimen without this fusion inhibitor.`

A 48-week safety analysis was also presented at IAS. Ninety-nine percent of patients experienced at least one injection site reaction. Manifestations of injection site reactions may include pain and discomfort, induration, erythema, nodules and cysts, pruritus, and ecchymosis. Aside from injection site reactions, the incidence of the three most common adverse events was less frequent in the FUZEON arm compared to control: they included diarrhea (37 patients experiencing the event per 100 years of patient exposure vs. 73), nausea (26 vs. 51) and fatigue (25 vs. 38). All of these measures were adjusted for length of patient exposure. (Further safety analyses at 48 weeks are ongoing. See `More About Fuzeon`section for additional safety information.)