The first patient was injected Monday in the world's firstPhase II gene therapy trial, Viagene Inc. officials said.
The San Diego company's gene transfer product, HIV-IT(V), will be tested in about 190 HIV patients at up to 15centers. Enrollment of patients in the two-year treatmentstudy should be accomplished over the next three to sixmonths, Viagene's president and CEO, Robert Abbott,told BioWorld.
If enrollment goes as planned, "by springtime, Viagenewill have treated more patients with gene therapyproducts than the sum of all other companies combined,"Abbott said.
He said data from the two-year study should be availablein about three years, but Viagene could start Phase IIItrials well before that.
"This is a big occasion for us because we've been morethorough and pensive in the way we went about thedesign of the clinical trials," Abbott said. "It represents ascientific, regulatory and clinical milestone for the genetherapy industry."
Patients in the triple-blind study were randomly assignedto three treatment groups, based on CD4 cell counts. Thefirst population of patients will have CD4 cell countsbetween 100 and 249, the second between 250 and 399and the third more than 400. Patients will get a series offour intramuscular injections at two-week intervals; thetreatment will be repeated every 16 weeks.
The goal is to induce cytotoxic T-lymphocyte, or CTL,activity. Abbott said studies have shown that HIVpatients who live longest have higher levels of CTLsagainst HIV, although for purposes of efficacy, CTLsnever have been correlated with disease progression.Three of four patients in an earlier study showed CTLincreases, two of them statistically significant.
HIV-IT (V) is a non-replicating murine retrovectorengineered to deliver the env and rev genes of HIV-1 tohealthy, non-HIV-infected cells, where the respectiveproteins are expressed.
William Lang is principal investigator at ViRx Inc., ofSan Francisco, where the first patient was injectedMonday. He said 15 or 16 patients are expected to betreated at that center.
"The basis of this treatment," Lang told BioWorld, "is tointroduce into cells not normally infected by HIV, genesthat cause those cells to produce proteins that get thisbranch of the cellular immune system activated. Not onlyagainst cells immunized," he said, "but, importantly, alsoagainst any cell bearing these HIV-related proteins.
"The real aim [of this gene therapy] is to delayprogression, to have a substantial effect on the delay ofprogression" Lang said. "If we could turn more peopleinto long-term survivors, we could regard it as aresounding success."
James Merritt, Viagene's vice president, medical affairs,said in a news release, "We have planned carefully forthis study. We have tested the safety of the product inover 70 patients in Phase I, and have consultedextensively with outside groups."
The Phase II trial will assess standard surrogate markers,such as CD4 counts and viral load, as well as someclinical endpoints. Abbott said the endpoint portion of thestudy will involve monitoring the incidence ofopportunistic infections in patients with the lowest CD4counts.
Abbott said interim analyses will be conducted after thesecond course of treatment, then periodically "until wesee the treatment effect that warrants consideration of aPhase III study."
Viagene is developing the product in collaboration withOsaka, Japan-based Green Cross Corp., which hasexclusive worldwide marketing rights to the finalproduct. In April 1991, Green Cross agreed to provide$37 million to support research and development of theproduct, and last April added another $10 million.Separately, Green Cross has a $4.75 million equityinvestment in Viagene, or a stake of about 11 percent. n
-- Jim Shrine
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