By Mary Welch

Vical Inc. is starting two Phase II trials for Leuvectin, a gene-based prostate cancer therapy, after promising results from a Phase I/II trial.

¿On the strength of the data, on both the surgical and radiation groups, we have progressed to multicenter Phase II trials,¿ said Alain Schreiber, president and CEO of the San Diego-based company. ¿The results have been encouraging, but it¿s too early to know how well it¿s working. But we are confident enough to start Phase II.¿

The Phase I/II trial focused on the prostate cancer patients¿ serum levels of prostate-specific antigen (PSA), which is used as a marker to detect and monitor the disease. Recent studies have championed PSA level as an important factor in predicting the rate of disease progression in postsurgical and post-radiation prostate cancer patients.

The trial¿s aim was to show that, by lowering or stabilizing PSA levels, the recurrence of prostate cancer could be delayed following surgery or radiation. The trial took place at the Jonsson Cancer Center at the University of California in Los Angeles.

Leuvectin is a gene-based treatment that uses the body¿s own immune system to fight cancer. Leuvectin contains plasmid DNA that encodes the potent immunostimulator interleukin (IL)-2, and a cytofectin to facilitate plasmid uptake by tumor cells. Recombinant IL-2 protein is FDA-approved for the treatment of advanced renal cell carcinoma and melanoma. When Leuvectin is injected into the tumor, it causes the malignant cells to produce and secrete IL-2 in the vicinity, stimulating the patient¿s immune system to destroy the cancer cells, Vical said.

¿These groups are high-risk candidates for the cancer to spread, but were still viable surgical candidates,¿ Schreiber said. ¿There was no visual spread beyond the prostate, but they had high PSA levels. Lab and biopsy results showed that they had a high likelihood of developing metastatic cancer. And, in fact, when three of the patients underwent surgery, the cancer had indeed metastasized.¿

On an outpatient basis, trial participants received two doses of Leuvectin, followed after several weeks by either radical prostatectomy (complete surgical removal of the prostate gland) or prostate biopsy (for patients with rising PSA after radiation therapy).

¿We were expecting the PSA levels to fall down to zero after surgery, because the prostate is removed,¿ Schreiber said. ¿What we didn¿t expect, and it is quite unusual, is that the PSA levels dropped significantly before surgery. When you manipulate the prostate, the PSA levels normally go up. We also were expecting to see some increase in PSA levels in at least some of the patients. So far, it¿s all been good.¿

In eight of the 12 patients scheduled for surgery, pre-surgical PSA levels decreased significantly after treatment with Leuvectin. Three patients had to be excluded from the trial because the disease had spread.

All nine who remained in the trial after surgery maintained negligible PSA levels after 11 months to 18 months, and are continuing.

In seven of the nine patients with progressive disease following radiation therapy, serum PSA levels decreased significantly after treatment.

¿Radiation is a different story,¿ he said. ¿We found an increase in PSA in most patients who had a single injection. With a second injection, the PSA levels slowed down or stabilized. They still increased, but not as fast. In our Phase II trial with radiation patients, they will be given repeated administration.

¿In both cases, it seems that adjuvant treatment with Leuvectin may postpone the need for more aggressive and difficult therapies, such as hormone therapies, where the treatment is far less tolerated than with Leuvectin,¿ he said.

There were few side effects with Leuvectin, namely rectal spotting.

Results from the Phase I trial were presented at the annual meeting of the American Urological Association in Dallas.

The new Phase II trials will take place at the University of California in Los Angeles and at the Cleveland Clinic Foundation in Ohio, and will include up to 60 patients, divided between presurgical patients and radiation-failure patients.

Prostate cancer is the second most fatal cancer in men. African-Americans are at significantly greater risk than Caucasians, and men over 65 account for more than 80 percent of all patients. Nearly 180,000 new cases and 37,000 deaths are expected in the U.S. this year.

There is no curative therapy once the tumor has grown outside the prostate capsule. Those who undergo surgery when the disease is still confined to the gland have an excellent chance of recovery; however, up to 40 percent who are considered candidates for radical prostatectomy will have adverse prognostic factors for disease reoccurrence after surgery.

Radiotherapy has had varying rates of success when used in the adjuvant setting.

Vical¿s stock (NASDAQ:VICL) closed Monday at $11.812, up $0.437. n