"Toxicities, and in particular lipodystrophy and lipoatrophy, are a real challenge for HIV treating physicians and patients and drug toxicities are the main reason why patients discontinue therapy" commented Professor David Cooper, Director, Australian National Centre for HIV Epidemiology and Clinical Research (NCHECR) St Vincent's Hospital, Sydney. "With FUZEON, we are now able to look into establishing a new standard of care for pre-treated patients and in Australia we are investigating other approaches to spare or reduce toxicity using FUZEON. First results from our toxicity sparing trial using FUZEON are expected to be presented later this year."
What is lipodystrophy/lipoatrophy?
Body fat changes in HIV are known as lipodystrophy and lipoatrophy. There are three general patterns of body fat changes that are seen in people with HIV who are taking combination anti-retroviral (ARV) therapy; gaining fat on the abdomen, between the shoulder blades or around the neck or in the breasts (lipodystrophy); losing fat from under the skin which becomes obvious in the face, arms, legs and buttocks (lipoatrophy); and a mixture of both fat gain and fat loss. These fat changes are often known as "fat redistribution" and can be accompanied by metabolic changes (rises in levels of fats and sugar in the blood).
Latest FUZEON data
This new analysis included DEXA (dual x-ray absorptiometry) body composition scans in a sub-group of patients in the TORO studies, which showed that those in the FUZEON arm (n =65) experienced little to no median changes from baseline in fat redistribution at 48 weeks, compared to patients taking a regimen that did not include FUZEON (n=12). There were no relevant differences between the two arms in the magnitude of changes for glucose, total cholesterol, LDL cholesterol and triglycerides. Previously presented safety analysis at 48 weeks showed that adding FUZEON to the treatment regimen did not exacerbate most of the known toxicities associated with other ARV's. In particular, the reported incidence of diarrhea in the FUZEON containing arm was approximately half that of the arm without FUZEON. There were no differences between the two arms in the magnitude of changes for glucose, total cholesterol, LDL cholesterol and triglycerides. Small differences were observed for insulin and very low-density levels.
With the introduction of FUZEON, physicians now have available four classes of anti-retroviral therapy and an important new option for pre-treated patients. The antiretroviral drug classes available prior to the introduction of FUZEON (the reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and the protease inhibitors) work inside the already infected CD4 cell. However, FUZEON works before the other classes of drugs, acting outside the immune cell and blocking the virus before it can enter. Based on the results presented at CROI, Roche is exploring clinical research to assess the benefits of adding FUZEON to nucleoside sparing regimens designed to decrease toxicities associated with HIV treatment. This approach is being supported by the NCHECR, the Australian research centre that pioneered research into risks of body fat distribution linked to lipodystrophy.
Notes to Editors:
Efficacy and Durability
The 48 week FUZEON data released earlier, demonstrated consistent and durable results for FUZEON where the overall response rate at week 48 was higher among patients on the FUZEON containing arm compared to the arm without FUZEON. Also the benefit of regimens containing FUZEON lasted three times longer than those without and patients exposed to fewer prior antiretrovirals had a longer time to virological failure compared with more extensively pre-treated patients.
Safety of FUZEON
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 the TORO studies, 98 percent of patients had at least one local injection site reaction over the course of 48 weeks. In this treatment-experienced patient population, 4 percent of patients at 48 weeks discontinued treatment with FUZEON as a result of injection site reactions.
An increased rate of some bacterial infections, primarily pneumonia, was seen in patients treated with FUZEON. It is unclear if this increased incidence is related to FUZEON use. The addition of FUZEON to background antiretroviral therapy generally did not increase the frequency or the severity of the majority of adverse reactions. The majority of adverse reactions were of mild or moderate intensity. Hypersensitivity reactions have occasionally been associated with FUZEON therapy and in rare cases have recurred on re-challenge.
Resistance to HIV drugs
It is estimated that in a single untreated person the virus can mutate to form around a billion new and potentially different versions of HIV every day. The incidence of drug resistant HIV among already treated patients is increasing at a disturbing rate. It was recently reported in one study that up to 50 percent of patients in North America are infected with a strain of the virus that has developed resistance to one or more anti-HIV drug.
Roche in HIV
Roche is at the forefront of efforts to combat HIV infection and AIDS, committed since 1986 to groundbreaking research and development of innovative new drugs and diagnostic technology. Saquinavir was the first Protease Inhibitor (PI) and was first introduced by Roche in 1995 in the US.
As a consequence of Roche's continuous research and development, the combination of boosted saquinavir with ritonavir (1000/100 mg twice daily) has shown encouraging results in the MaxCmin 1 trial with high efficacy and an excellent safety and tolerability profile. Saquinavir/r was approved in the EU in August 2002. Viracept (nelfinavir), a leading PI is supplied by Roche outside the US and Canada. In first-line HIV therapy, Viracept delivers consistent long-term efficacy and safety. When used first line, Viracept also allows the subsequent use of both NNRTIs and other PIs for most patients due to its unique resistance pattern. FUZEON received approval from the US Food and Drug Administration (FDA) in March 2003, and from the European Commission and Switzerland in May 2003 and Canada in July 2003.
The viral load measurements in the clinical trials for FUZEON were performed using the AMPLICOR HIV-1 MONITOR TEST, version 1.5. This test from Roche Diagnostics is considered to be a highly sensitive measurement of the amount of HIV circulating in a patient's blood ("viral load"). With a limited number of treatment regimens available, the accurate monitoring of viral load levels is essential to establish and monitor the effectiveness of therapeutic regimens and assess the potential onset of drug resistance.
Roche is a committed partner of the Accelerating Access Initiative to increase access to HIV care in sub-Saharan Africa and the world's Least Developed Countries. For more information on Roche policy and pricing of HIV protease inhibitors for these regions and research in HIV, visit www.roche-hiv.com.
About Roche
Headquartered in Basel, Switzerland, Roche is one of the world's leading innovation-driven healthcare groups. Its core businesses are pharmaceuticals and diagnostics. Roche is number one in the global diagnostics market and is the leading supplier of pharmaceuticals for cancer and a leader in virology and transplantation. As a supplier of products and services for the prevention, diagnosis and treatment of disease, the Group contributes on a broad range of fronts to improving people's health and quality of life. Roche employs roughly 65,000 people in 150 countries. The Group has alliances and research and development agreements with numerous partners, including majority ownership interests in Genentech and Chugai.
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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(R), 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 website at 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," "anticipate", "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.
For more information, please contact:
Jennifer Wilson
T: +41 61 688 9632
jennifer.wilson@roche.com
Harriet Farmer
T: +44 207 611 3618
harriet.farmer@ketchum.com