Immune Response Corp. and its partner, Rhone-Poulenc Rorer,presented long-awaited data from the Phase II/III clinical trialon their HIV-1 immunotherapeutic vaccine Wednesday at theNinth International AIDS Conference in Berlin.
The bottom line: The data on the putative vaccine's ability toinfluence the viral burden in HIV-infected patients arestatistically significant, but not overwhelmingly so. They're notconclusive, either, and point the way to the need for moreclinical trials of the vaccine over longer time periods todetermine whether it has a clinical effect on diseaseprogression.
"We are seeing trends which are in a direction that isworthwhile pursuing," commented Jonas Salk, who proposedthe strategy of preventing or slowing the progression of HIVinfection by stimulating the immune system to attack the virusearly after infection.
Given the anticipation surrounding Wednesday's "event" inBerlin (which included an international teleconference),anything less than spectacular would have proved adisappointment to many -- and it did.
The stock (NASDAQ:IMNR), which had stopped trading brieflyon Wednesday pending the news, dropped $5.63 for the day asclose to 5 million shares traded hands. It closed at $16 a share.The shares were also down $3 on Tuesday.
"Scientifically, the data are encouraging, the effect of thevaccine on viral load is very compelling," analyst EdmundDebler of Mehta & Isaly told BioWorld. "But if you include allthe hype, the promises and the near-term needs, it'sdisappointing.
"Overall, it looks like this will not be enough for FDA approval,"he said. Debler said that his firm has not changed its "neutral"rating on Immune Response.
The HIV immunotherapeutic vaccine, which is being developedby Immunization Products Ltd. (IPL), a joint venture betweenImmune Response of San Diego and Rhone-Poulenc Rorer ofPennsylvania, is an envelope-depleted, chemically inactivatedand irradiated preparation of the virus.
It's been in human clinical trials since 1987, during which timethe vaccine has proven safe. "It's not associated with theincreased progression of HIV disease by any means," saidAlexandra Levine, chief of hematology at the University ofSouthern California School of Medicine and a principalinvestigator on the clinical trials. And it was also able to elicitan enhanced immune response. "Enhanced production ofantibodies against HIV in treated patients is statisticallygreater than in placebo controls," said Levine.
In addition, the data presented in Berlin showed that thevaccine stabilizes the viral burden (the rate of increase of HIVin peripheral blood lymphocytes) over time. "There's a trendtoward stability that is statistically significant," Levine said.
Those data were from a one-year surrogate-marker study on103 asymptomatic HIV-infected individuals. A statisticallysignificant difference was observed in the rate of increase ofHIV in the peripheral blood -- as proviral sequences integratedinto lymphocytic DNA -- in treated as compared to placebocontrols when measured by an assay employing polymerasechain reaction (PCR) technology.
The findings didn't stand up to an assay less sensitive than PCR,however. When the scientists used a qualitative co-cultivationmethod to measure viral burden, they found no significantdifferences between the treated and control groups.
The PCR data demonstrated that the placebo group had a viralburden that increased 48 percent over baseline over time,while the treated group's viral burden, overall, increased about10 percent over baseline for the same time period, according toLevine.
Levine explained that this group actually consisted of threepopulations; one showed a decrease in viral burden, one wasstable, and the third had an increased burden. "Fewer treatedindividuals showed an increase, and a greater number showeda decrease," added Salk.
Moreover, the difference in the viral burden between treatedand control groups was greater during the second six months ofthe study than the first six months, the companies said.
The patients were given three doses of vaccine, 100micrograms per dose, at zero, three and six months. Overall, theresearchers analyzed samples from 12 different time pointsover the course of the study, with 50 patients in each timepoint, said Dennis Carlo, Immune Response's executive vicepresident and chief scientific officer.
"These surrogate marker studies are consistent with thepossibility that treated individuals can be disease free for alonger time," Levine said.
The companies also said they found a statistically significantincrease or stabilization in the body's cell-mediated immuneresponses to HIV proteins in the vaccine-treated group ascompared to control groups.
"The next clinical study will be designed to look at clinical endpoints," Levine said. "A follow-up period of one year is tooshort to see the clinical consequences of the immunologicalresponses we've observed."
-- Jennifer Van Brunt Senior Editor
(c) 1997 American Health Consultants. All rights reserved.