Healthcare Industry News: ritonavir
News Release - June 26, 2006
New Data Show FUZEON(R) Continues to Provide Significant Immune System Benefits in Patients Despite Ongoing Viral Replication
NUTLEY, N.J. & MORRISVILLE, N.C.--(HSMN NewsFeed)--June 26, 2006--A new analysis of the TORO studies presented in an oral session at the 15th International HIV Drug Resistance Workshop in Sitges, Spain demonstrate continued CD4 cell increases in some patients who continued with FUZEON® (enfuvirtide)-based regimens despite virologic failure and FUZEON resistance. Of further note was the correlation of certain FUZEON resistance mutations with the observed increases in CD4 immune cells, corroborating the findings of other investigators presented in February 2006 at the Conference on Retroviruses and Opportunistic Infections. Co-developed by Roche and Trimeris (Nasdaq: TRMS ), FUZEON is the first and only HIV fusion inhibitor. Unlike other HIV drugs that work after HIV has entered the human immune cell, FUZEON works by blocking the virus from entering the human immune cell."Characterizing the impact of FUZEON-related resistance mutations is an important endeavor, both clinically and scientifically," said Carlo Federico Perno, M.D., Ph.D., Professor of Virology at the University of Rome Tor Vergata, Italy. "This new analysis from the TORO studies confirms a similar analysis from our research and shows that FUZEON-related resistance mutations may be associated with maintenance of CD4 cell counts or even continued CD4 improvements in some patients."
More About the Study
The new data is based on an analysis of patients who experienced virological failure in the TORO Phase III studies with FUZEON (n=355). Complete CD4 cell count data for up to 96 weeks following virologic failure was available for 134 patients. Using genotypic analysis, these patients were divided into subgroups based on treatment-emergent resistance mutations to FUZEON that occur in the region of gp41 amino acids 36-45. When compared to levels before initiation of therapy with FUZEON, patients either maintained CD4 cell gains or exhibited statistically significant and clinically meaningful increases in CD4 cell counts over 48 weeks of additional FUZEON therapy despite virological rebound. Of note, patients (n=58; 43%) with a particular mutation, the V38A, exhibited additional increases in CD4 cell count for 48 weeks after virologic failure to FUZEON, while patients (n=68; 51%) with other mutations including N43D maintained their CD4 cell benefit from baseline through 48 weeks after virologic failure while on FUZEON. Only patients with the Q40H mutation (n=8; 6%) had declines in CD4 cells after virologic failure.
A separate poster presentation at the workshop shed further light on one of these mutations, N43D and its ability to impact viral fitness. This work shows that this mutation causes significant structural defects in regions of the gp41 HIV virus envelope protein, decreasing the stability of interactions which are critical for the viral fusion and entry into CD4 cells. Such structural changes to the HIV virus caused by the N43D mutation may illustrate the cost to the virus of circumventing FUZEON in order to continue replication. These observations support the important role that the envelope plays in HIV replication and pathogenesis and point to unique contributions that entry inhibitors may make to treatment strategies.
Resistance Profiles of Next-Generation Fusion Inhibitor Candidates
Roche and Trimeris are developing two next-generation fusion inhibitor peptide candidates, TRI-999 and TRI-1144, which were selected by the companies for progression into full pre-clinical development in early 2006. The compounds have shown potent antiviral activity and durable control of HIV replication in vitro, with desirable pharmacokinetic properties in vivo supporting the objective of achieving once-weekly dosing for these novel fusion inhibitors. New data presented at the resistance workshop show that the compounds exhibit substantial potency and considerably greater consistency of activity in vitro against viruses that were sensitive to FUZEON, and more importantly, those with substantial resistance to FUZEON.
Facts About FUZEON
Administered via one 90 mg subcutaneous injection twice-daily, FUZEON is the first and only fusion inhibitor for the treatment of HIV. Unlike other HIV drugs that work after HIV has entered the human immune cell, FUZEON works outside the CD4 cell, blocking HIV from entering the cell. For this reason, FUZEON is effective in treatment-experienced patients who have developed resistance to other anti-HIV drugs, though patients may still develop resistance to FUZEON. FUZEON was granted accelerated approval by the U.S. Food and Drug Administration (FDA) in March 2003 on the basis of 24-week data, and was granted traditional (full) approval on Oct. 15, 2004 on the basis of long-term 48-week data.
Recently updated Antiretroviral Treatment Guidelines from the U.S. Department of Health and Human Services (DHHS) established the use of FUZEON and an active ritonavir-boosted PI and to achieve undetectable HIV in treatment-experienced patients. These new guidelines cited several recent clinical trials of new boosted PIs in treatment-experienced patients, demonstrating better and more prolonged virologic response in patients taking FUZEON as part of a regimen that includes these new boosted PIs.
Injection Site Reactions (ISRs): ISRs are the most common adverse events associated with FUZEON. ISRs occurred in 98% of patients studied and 4% discontinued FUZEON due to ISRs over 48 weeks. Signs/symptoms may include pain and discomfort, hardened skin, redness, bumps, itching and swelling. Eleven percent of patients had local reactions that required analgesics or limited usual activities.
Pneumonia: An increased rate of bacterial pneumonia was observed in subjects 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. Patients with HIV infection should be carefully monitored for signs and symptoms of pneumonia. Risk factors for pneumonia included low initial CD4 cell count, high initial viral load, intravenous drug use, smoking and a prior history of lung disease.
Hypersensitivity Reactions: Systemic hypersensitivity reactions have been associated with FUZEON therapy and may recur on rechallenge. Hypersensitivity reactions have included individually and in combination: rash, fever, nausea and vomiting, chills, rigors, hypotension and elevated serum liver transaminases. Other adverse events that may be immune mediated and have been reported in subjects receiving FUZEON include primary immune complex reaction, respiratory distress, glomerulonephritis and Guillain-Barre syndrome.
Other Adverse Events: The events most frequently reported in patients receiving FUZEON plus an optimized background regimen were diarrhea (32%), nausea (23%) and fatigue (20%). These events were seen at a lower incidence in patients taking a FUZEON-based regimen compared to those receiving an optimized background regimen without FUZEON when taking into account the uneven number of patients in each arm and the length of time they are in that arm. As measured in number per 100 patient years, the incidence was: diarrhea (38 per 100 patient-years in subjects receiving FUZEON-based regimens vs. 73 per 100 patient-years in patients who did not receive FUZEON), nausea (27 vs. 50, respectively) and fatigue (24 vs. 38, respectively).
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.
Roche and Trimeris are working together to discover, develop and commercialize the next generation of HIV fusion inhibitors.
About Roche
Hoffmann-La Roche Inc. (Roche), based in Nutley, N.J., is the U.S. pharmaceuticals headquarters of the Roche Group, one of the world's leading research-oriented healthcare groups with core businesses in pharmaceuticals and diagnostics. For more than 100 years, the Roche Group has been committed to developing innovative products and services that address prevention, diagnosis and treatment of diseases, thus enhancing people's health and quality of life. An employer of choice, in 2005, Roche was named one of Fortune magazine's Best Companies to Work For in America, one of the Top 20 Employers (Science magazine), ranked as the No. 3 Best Company to Work For in NJ (NJ Biz magazine), the No. 1 Company to Sell For (Selling Power), and one of AARP's Top Companies for Older Workers. For additional information about the U.S. pharmaceuticals business, visit our websites: http://www.rocheusa.com or www.roche.us.
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, approved in the U.S., Canada and European Union, is the first in a new class of anti-HIV drugs called fusion inhibitors. Trimeris is developing FUZEON and future generations of peptide fusion inhibitors in collaboration with F. Hoffmann-La Roche Ltd. For more information about Trimeris, please visit the company's Web site at http://www.trimeris.com.
Trimeris Safe Harbor Statement
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; we are dependent on third parties for the sale, marketing and distribution of our drug candidates; 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 10, 2006 and its periodic reports filed with the SEC.
Source: Roche
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