By Kim Coghill
The Immune Response Corp. (IRC) said Monday it will publish data in a European journal showing that patients treated with Remune (HIV-1 Immunogen) show a reduction in viral load regardless of concomitant antiretroviral drug therapy.
IRC¿s stock (NASDAQ:IMNR) closed Monday at $2.58, up 95 cents, or 58 percent.
The study shows Remune induces HIV-specific, T-helper-cell immune responses that correlate with the amount of HIV in the bloodstream. The data will appear in the April edition of HIV Medicine, the journal of the European AIDS Clinical Society and the British HIV Association.
¿The study had a number of design issues related to it, and it provided a basis for some of the ongoing, newer studies which we think are better designed and allow us to optimize the relationship ¿ that is, if these stronger immune responses, that we are hopeful for, will translate into lower viral load in some of the ongoing studies,¿ said Ronald Moss, IRC¿s vice president of medical and scientific affairs.
The protocol-defined, random cohort involved 252 HIV-positive patients who received injections of either Remune or a placebo, in addition to unrestricted antiretroviral drug use. A 2,500-patient, multicenter, double-blind, adjuvant-controlled, clinical endpoint Phase III study begun in 1996 included this cohort study, which was designed to determine the relationship between viral load and HIV-specific immunity.
Viral load was measured as HIV-1 plasma RNA levels every 12 weeks, more frequently than in other patients in the larger study, whose viral load was measured every 24 weeks. In the Remune-treated group, a significantly greater decline in viral load (p<0.05) at multiple time points was observed. Differences in viral load were not significant for the first two time-points but were observed at week 36 (p=0.01), and were maintained at weeks 48 (p=0.02), 60 (p=0.02), 84 (p=0.001), 96 (p=0.004), and 120 (p=0.03).
The authors believe that the apparent 36-week ¿lag time¿ between the initial treatment with Remune and a significant reduction in viral load may suggest that the immune system requires a period of time after immunization to organize specific immune forces against the virus.
Lymphocyte Proliferation Assays (LPAs) were also performed on blood samples taken every 24 weeks. LPAs are a common measure of the ability of the immune system to respond to HIV via T helper cells. LPA test results indicated that HIV-specific T helper cell immune responses were generated only in the Remune-treated group (p<0.0001).
Moss said Remune likely is best used in combination with antiretroviral drug therapy, and is probably the most effective in early disease. ¿You need a competent immune system to respond to this drug,¿ he told BioWorld Today. ¿It can¿t be used on end-stage disease.¿
Because the product is delivered in the form of a shot every third month, Moss said, ¿there¿s an upside in terms of developing countries. There¿s some potential to give this on a large scale without complicated regimens. We¿ve given this to thousands of individuals and we believe it is safe and nontoxic, and we believe there is compliance when giving something every three months,¿ he said.
¿The side effects are similar to a pediatric vaccine where there¿s some redness to the arm,¿ he added.
Remune currently is the subject of several clinical trials, including a Phase II trial in Spain and a Phase III trial sponsored by the company¿s partner, Agouron Pharmaceuticals Inc., of La Jolla, Calif., to evaluate Remune¿s effect on viral load when administered in combination with potent antiviral drug therapy. Impact on viral load is a measure accepted by the FDA for approval of Remune.
Moss said the Phase III study is due to be unblinded in 2002 and the Phase II study should be unblinded in May or June. ¿We are hopeful that the Phase II study will be somewhat supportive of the Phase III study,¿ he said. ¿We believe those studies will be the proof of the pudding.¿
A Phase III trial of Remune was halted in May 1999, when an independent data safety monitoring board determined that the 2,500-patient, 120-week study could not meet its primary endpoint of reducing the rate of disease progression. (See BioWorld Today, May 18, 1999.)
A year later, the company stopped enrollment in a 472-patient Phase III trial of the drug with highly active antiretroviral therapy, in order to adjust the protocol. (See BioWorld Today, June 22, 2000.)