Long-term data at ICAAC reveals how best to use FUZEON in pre-treated patients for maximum benefit
Basel, September 15 - The one year analysis of the pivotal fusion inhibitor trials (TORO 1 & 2) presented today at ICAAC show physicians how best to use FUZEON (formerly known as T-20) for pre-treated HIV/AIDS patients. Regimens containing FUZEON significantly outlasted those without FUZEON and longer-term benefits are achieved with FUZEON in patients who are less treatment experienced.
"Being a person living with HIV, one is always aware of becoming resistant to therapy and running out of alternatives. FUZEON was a new option that became available and I was fortunate enough to start therapy before things were desperate. I have been on FUZEON and other drugs for 2 years now and am successfully maintaining my HIV at below detectable levels, " said Micael Hermansson, a person living with HIV.
Results: Consistent and Durable over One Year
- The overall response rate at week 48 demonstrated a significantly higher treatment benefit for patients on the FUZEON containing arm compared to the arm without FUZEON, confirming week 24 data
- Almost all patients who achieved undetectable levels of HIV (<400 copies/mL) at 24 weeks maintained the response at 48 weeks.
- Long-term data showed that the benefit of regimens containing FUZEON lasted three times longer than those without.
- Patients exposed to fewer prior antiretrovirals had a longer time to virological failure compared with more extensively pre-treated patients
One Year FUZEON Data Begs The Question - Why Risk The Wait?
"This analysis of FUZEON is extremely good news for all pre-treated HIV patients and clearly shows physicians how to gain maximum benefit from FUZEON. When FUZEON is used earlier in treatment, for example following second virologic failure, patients derive longer benefit from FUZEON versus waiting for failure of subsequent regimens" said Dr Trottier, Clinique l'Actuel, Montreal, Canada.
Lower Rate of GI Side Effects in FUZEON Containing Regimens
"Adverse events are a major reason for discontinuation of antiretroviral therapies," said Dr Eron. " However, what we observed was that the addition of FUZEON did not exacerbate most of the adverse events commonly associated with currently available antiretrovirals and it is interesting to note that patients taking a FUZEON containing regimen, experienced approximately a 50% reduction in diarrhoea, compared with those taking the individualised regimen without FUZEON".
48 week safety data also presented at ICAAC by Dr Eron, confirm the safety profile and tolerability of FUZEON in a multi-drug resistant, treatment-experienced population. Injections site reactions (ISRs) were the most common side effect associated with FUZEON. While most patients experienced ISRs at some point during the study, those reactions were generally mild to moderate with less than 5 % of patients discontinuing treatment as a result.
FUZEON Available Now, Manufacturing Expansion
Improved manufacturing has resulted in greater supply output of FUZEON being available than previously anticipated. A process modification which has been filed with regulatory authorities in the USA and EU is now leading to improved outputs of FUZEON active pharmaceutical ingredient (API).
Installation of a second chromatography column was achieved ahead of schedule. This is currently undergoing validation and will have the potential to further increase the capacity at Roche's facility in Colorado. Plans are in place for significant further expansion of the Boulder facility that will increase the current planned capacity of 3.7 metric tons per year to around 6 metric tons per year in 2005.
T-1249 - An Investigational Fusion Inhibitor for the Future
A new study presented at ICAAC today shows that T-1249, a follow on compound to the world's first fusion inhibitor, FUZEON, has potent anti-retroviral activity.
"We at Trimeris, along with our partner Roche, are applying our experience from the development of FUZEON to our continuing search for new treatment options," said Dr Dani Bolognesi, Chief Executive Officer, Trimeris. "The results from this study of T-1249 demonstrate that fusion inhibitors constitute an expanding class of anti-HIV drugs with the potential to be used sequentially."
Study Design and Results
This study evaluated the antiviral activity and safety of T-1249 over a 10-day period in 53 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 1.26 log10 copies/mL. There were no serious adverse events or grade 3 or 4 laboratory abnormalities related to T-1249 in the trial.
"It is important to stress that T-1249 is in early-stage development and the timing of the initiation of the next T-1249 phase II studies will be dependent upon a combination of factors including, scale-up of manufacturing, completion of formulation work to support chronic dosing, finalization of protocols and regulatory discussions. Therefore, we cannot provide an exact timing for the start of the next clinical trial," said Dr David Reddy, Lifecycle Leader Fusion Inhibitors.
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Notes to Editors:
Study Design
TORO 1 (T-20 vs. Optimised Regimen Only) and TORO 2 are randomised, open-label trials that enrolled approximately 1,000 patients at 112 centres internationally. Patients in the trials were treatment-experienced and/or had documented resistance to each of the three classes of currently available antiretrovirals. In addition, each patient was required to have a HIV level of greater than 5,000 copies/mL.
At entry, genotypic and phenotypic resistance testing was used to aid in the selection of an antiretroviral regimen, consisting of three to five drugs, including if appropriate, up to two newly approved or investigational drugs. After selection of the regimen, patients were randomised 2:1 to receive either the regimen in combination with FUZEON or the regimen alone. Patients randomized to FUZEON receive FUZEON administered as one 90 mg subcutaneous self-injection twice-daily.
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.
FUZEON indication in the European Union
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."
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. T-1249 is being co-developed by Roche and Trimeris.
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 62,000 people in 150 countries. The Group has alliances and research and development agreements with numerous partners, including majority ownership interests in Genentech and Chugai.
All trademarks used or mentioned in this release are legally protected.
About Trimeris
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
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 authorisations and product commercialisations; 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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