By Randall Osborne
West Coast Editor
Having reaped less than encouraging interim results from data regarding the first 37 patients of a potential 80 in a Phase II metastatic kidney cancer trial with gene-based Leuvectin, Vical Inc. said it will scrap the current study and start a new one, hoping for better efficacy.
¿It¿s a learning experience,¿ said Alan Engbring, director of investor relations for San Diego-based Vical. ¿What we¿ve learned here is something about our manufacturing method and product configuration.¿
The San Diego-based firm¿s stock (NASDAQ:VICL) dropped 22 percent on the news, closing Friday at $13, down $3.65, although Engbring blamed the loss in value ¿as much or more¿ on a downgrade of the stock from ¿market outperformer¿ to ¿marker performer¿ by Goldman Sachs & Co. in New York.
¿I¿m not saying we didn¿t see any efficacy, I¿m saying we saw less than expected,¿ Engbring said, adding that the treatment ¿is not expected to get to the market even within the next couple of years, and it wasn¿t before.¿
In the halted trial, the formulation process for Leuvectin was different from the drug used in earlier studies that proved the drug¿s safety in more than 235 patients, Engbring noted.
¿Let¿s say we have a strong suspect [in what went wrong],¿ Engbring told BioWorld Today. ¿In this trial, we switched to a single-vial formulation as opposed to a multivial formulation, and increased the dose fourfold. That appears to create a problem.¿
Physicians like the single-vial formulation, since it requires no mixing, and pre-mixing the smaller batches posed no problem, Engbring said.
¿But when we mix it in large batches, we¿re getting some aggregation of product,¿ he said. ¿You can¿t offset this completely [with larger doses]. If you¿re delivering something that¿s aggregating, the solution is not holding enough of the stuff.¿
He added that the trial drug was ¿well within manufacturing specifications, but probably within the lower range. If you have an acceptable range, you release it and start the trial. This is one of the reasons you do trials. It¿s better to find it here than in Phase III, or out on the market. Maybe one of the things we need to do is tighten up the release specifications a bit.¿
Leuvectin, injected directly into tumors, uses lipid DNA complex with a gene encoding interleukin-2 to stimulate an immune response. An even stronger version of the drug will be deployed in the new trial. Engbring said he didn¿t know when that would begin.
¿I can¿t put a time frame on it, but it¿s going to be top priority,¿ he said. ¿We haven¿t come anywhere close to a maximum tolerated dose.¿
Recombinant IL-2 protein is an FDA-approved anticancer agent but, when given systemically, often carries serious side effects. Leuvectin gets around that by delivering the IL-2 locally.
¿I don¿t think of it as a vaccine, because we¿re not delivering a tumor-specific antigen here,¿ Engbring said.
Vical¿s naked DNA direct gene delivery technology is based on research that showed certain muscle tissue can absorb genetic material directly, without viral components, and then express a desired protein for long periods. The company designs plasmid loops, which are DNA segments with their ends attached, to carry the gene encoding the protein of interest, as well as short segments of DNA that control the rate and location of protein expression.
The company has other products in its pipeline. Vaxid, a naked DNA vaccine designed to prevent relapse of B-cell lymphoma, is in Phase I/II testing. Another naked DNA vaccine, this one for metastatic melanoma, is in Phase I/II testing, through a collaboration with the National Cancer Institute.
Engbring said the setback with Leuvectin might even be called a shortcut, since the original plan was to start another trial with a higher dose anyway. The interim examination was built into the trial as a ¿go or no-go decision point,¿ he said. ¿It¿s a fairly routine matter, in and of itself.¿