Results with New Integrase Inhibitor Plus Fuzeon and Boosted Protease Inhibitor Show Remarkable Undetectable Rate of 98 Percent in Treatment-Experienced HIV Patients
FUZEON, co-developed by Roche and Trimeris (Nasdaq: TRMS), is the first and only fusion inhibitor available for the treatment of HIV. Raltegravir (formerly known as MK-0518) is a novel investigational integrase inhibitor being developed by Merck & Co., Inc., while darunavir (Prezista(R)) is a commercially available, ritonavir-boosted protease inhibitor, marketed by Tibotec Therapeutics.
Pivotal Phase III results from two clinical trials with raltegravir in treatment-experienced patients (BENCHMRK 1 and 2), including subset analyses from the two studies combined, were reported for the first time at CROI. Patients enrolled in studies received 400 mg of raltegravir twice-daily in combination with an optimized background regimen of anti-HIV drugs. (FUZEON and darunavir were among the agents available as part of a patient's background regimen.)
Although international treatment guidelines have established undetectable viral levels of less than 50 copies/mL as the goal of therapy in treatment-experienced patients, the reported subset results for raltegravir reflect a less stringent definition of less than 400 copies/mL. Reported response rates (proportion of patients achieving undetectable HIV of less than 400 copies/mL) at 16 weeks in key patient subsets receiving different anti-viral regimens include:
-- FUZEON and darunavir/r with raltegravir: 98 percent (n=44)
-- FUZEON and darunavir/r without raltegravir: 87 percent (n=23)
-- Raltegravir without either FUZEON or darunavir/r: 74 percent (n=191)
-- Background regimen without raltegravir, FUZEON or darunavir/r: 29 percent (n=90)
Because FUZEON and/or darunavir/r were included in a patient's background regimen only at the judgement of the investigator after consideration of individual patient factors - such as CD4 count, degree of protease inhibitor resistance, and activity of other agents in the background regimen - the full meaning of these relative response rates is unclear. Generally, previous studies have shown that patients who receive FUZEON as part of the background regimen have more advanced disease and demonstrate a higher degree of drug resistance, with fewer active treatment options, than other treatment-experienced patients. Consequently, these subsets do not represent randomized comparisons of background treatment options with or without raltegravir that permit an accurate assessment of the relative benefits of one treatment strategy over another. A fuller understanding of these subset analyses will be possible after additional detail describing baseline treatment and disease characteristics of the patients in each subset is available.
"Despite several caveats surrounding the subset analyses, these promising new data herald a new era for HIV patients who are very treatment-experienced and who - with few exceptions - should be able to experience complete virologic suppression with FUZEON, darunavir and raltegravir," said James A. Thommes, M.D., Sr. Medical Director, Roche. "Importantly, the results also show that a high percentage of patients who received FUZEON and darunavir/r without raltegravir also achieved an undetectable viral load - a key consideration for patients and physicians who lack access to raltegravir through clinical studies."
According to Merck, raltegravir was generally well-tolerated with a safety profile comparable to placebo; few adverse experiences led to discontinuation.
Facts About FUZEON
Administered via one 90 mg 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.
FUZEON is indicated for use in combination with otherantiretroviral agents for the treatment of HIV in treatment-experienced patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy.
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. 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 complexreaction, respiratory distress, glomerulonephritis and Guillain-Barre syndrome.
Administration with Biojector(R)2000: Nerve pain (neuralgia and/or parethesia) lasting up to six months associated with administration at anatomical sites where large nerves course close to the skin, bruising and hematomas have occurred with the use of the Biojector 2000 needle-free device for administration of FUZEON. Patients receiving anticoagulants or persons with hemophilia, or other coagulation disorders, may have a higher risk of post-injection bleeding.
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 more than 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.
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 2006, Roche was named one of the Top 20 Employers (Science magazine), ranked the No. 1 Company to Sell For (Selling Power), and one of AARP's Top Companies for Older Workers, and in 2005, Roche was named one of Fortune magazine's Best Companies to Work For in America. 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.
Posted: March 2007