Phase III Results Of Immune-Based Therapy From Immunex
SEATTLE/VICTORIA, B.C., CANADA - Immunex Corporation [Nasdaq: IMNX] announced today that LEUKINER (sargramostim; GM-CSF) maintained viral suppression and extended the duration of antiretroviral therapy utility in patients with AIDS whose viral loads were less than 30,000 copies/mL at study entry. In addition, while LEUKINE did not decrease "AIDS clinical events" including opportunistic infections, bacterial pneumonia or death, it did reduce the incidence of all infections and death. The results of the Phase III trial were presented at the Eighth Canadian Conference on HIV/AIDS Research.
The 309-patient, Phase III, double-blind, randomized, placebo-control trial evaluated the impact of LEUKINE on the incidence of opportunistic infections, the rate of survival and changes in viral load, CD4+ T cell counts and absolute neutrophil counts. Changes in therapeutic regimens also were monitored in this study. All patients in the trial were diagnosed with late-stage AIDS (patients entering the study had CD4+ T cell counts of less than 50, or less than 100 with a prior AIDS-defining opportunistic infection). Patients were stratified into two groups based on baseline viral loads of below or above 30,000 copies/mL. Patients received either LEUKINE or a placebo three times per week for six months as an adjunct to standard antiretroviral therapy. Physicians were permitted to change antiretroviral therapy to manage the patient's viral load. Forty-five percent of patients participated in an optional, blinded study extension up to 20 months of treatment.
Among 115 patients with viral loads less than 30,000 copies/mL, 81 percent of the LEUKINE patients were able to remain on the same antiretroviral regimen and maintain baseline level of viral suppression throughout the duration of the study as compared to 62 percent of the patients receiving placebo. In the six-month study, patients with undetectable virus (less than 400 copies/mL) who received LEUKINE were more likely to maintain undetectable viral loads than patients receiving placebo. In 57 patients with undetectable virus at study entry, 83 percent of LEUKINE patients continued to maintain undetectable viral load at 24 weeks as compared to 54 percent of placebo patients.
"Despite the success of current anti-HIV therapies, there is an increasing incidence of treatment failure," said Jonathan Angel, M.D., principal investigator and infectious disease specialist at Ottawa General Hospital in Ontario, Canada. "Patients are failing existing antiretroviral regimens for at least two reasons. One is a lack of patient adherence to the strict dosing regimens of antiretroviral drugs. Another reason is that HIV mutates - becoming resistant to a single antiretroviral agent, or whole class of these therapies. This new data suggests that it is possible to extend the time patients can maintain viral suppression and their responses to an antiretroviral regimen."
LEUKINE belongs to a developing class of immune-based therapies being studied in people with HIV/AIDS. Laboratory research has shown that LEUKINE protects immune system cells from HIV by blocking the virus from entering uninfected cells. Previous clinical research has extended this observation and shown that LEUKINE can reduce viral load in combination with mono or dual nucleoside analog therapy and can reduce viral resistance to at least one of these therapies, zidovudine (AZT).
"While antiretroviral therapies attack the virus, immune-based therapies focus on the immune system cells," said Ann Hayes, M.D., senior vice president of medical development at Immunex. "Immune-based therapies have the potential to protect the immune system from HIV infection, ensure that infected cells remain susceptible to antiretroviral therapies, and ultimately re-establish the human immune system's ability to fight HIV and infections on its own."
People with AIDS have very low cell counts resulting in a compromised immune system and very limited defense against infection. Analysis of the incidence of infections and death (including opportunistic infections used to define a diagnosis of AIDS and other infections such as bacterial pneumonia, bacteremia and urinary tract infections) determined that LEUKINE increased the median time to first event by 41 days in both cohorts. Further, the incidence of these events was lower in the LEUKINE group (67 percent) as compared to the placebo group (78 percent).
The Phase III study also found that patients in both cohorts treated with LEUKINE nearly doubled mean CD4+ T cell counts from 51 at the start of the study to 94 at six months while patients in the placebo group had an increase in cell counts from 50 to 71. Also, at six months, LEUKINE increased mean absolute neutrophil counts by 884 as compared to 266 among patients receiving placebo.
"We will be reviewing the results of the LEUKINE Phase III trial with the FDA this spring," said Peggy Phillips, Immunex senior vice president of pharmaceutical development.
LEUKINE was generally well tolerated. Side effects occurring more frequently with LEUKINE than placebo included injection site reactions and weight loss. Injection site reactions were mostly mild and did not require treatment; weight decreases were typically mild.
The results described herein are based on investigational data analyzed by Immunex. These data have not been reviewed by the U.S. Food and Drug Administration (FDA) as part of an application for regulatory approval. LEUKINE is not indicated for use in HIV, however, the company has been working aggressively since 1996 to evaluate the product's mechanism of action and role in HIV treatment. Full prescribing information for LEUKINE can be obtained by calling 1-800-IMMUNEX or at www.immunex.com.
The most recent estimate from the Centers for Disease Control indicates that there are 650,000 to 900,000 Americans currently living with HIV, which equates to 1:160 men and 1:800 women over age 13.
Immunex is a biopharmaceutical company dedicated to developing immune system science to protect human health. The company's products offer hope to patients with cancer, inflammatory and infectious diseases.
American Home Products owns a majority interest in Immunex. AHP is one of the world's largest research-based pharmaceutical and health care products companies. It is a leader in the discovery, development, manufacturing, and marketing of prescription drugs and over-the-counter medications. It is also a global leader in vaccines, biotechnology, agricultural products and animal health care.
NOTE: This news release contains forward-looking statements that involve risks and uncertainties, including risks associated with clinical development, regulatory approvals, product commercialization and other risks described from time to time in the SEC reports filed by Immunex, including the most recently filed Form 10K.