Employing a slash-and-burn technique to streamline its pipeline, Vical Inc. said it is not completing its Phase III low-dose trial of Allovectin-7 in metastatic melanoma due to the improbability of it achieving desired endpoints, is closing a Phase II trial of Allovectin-7 for early stage head and neck cancer, and would no longer develop Leuvectin for prostate or kidney cancer.
It was just last year when Vical discontinued a Phase II trial of Leuvectin in kidney cancer, saying it would start a new one and hope for better efficacy. Now, however, Vical, of San Diego, officially has just one clinical program - the Phase II high-dose, multiple-tumor Allovectin-7 trial. (See BioWorld Today, April 23, 2001.)
In a conference call Wednesday, Vical CEO and President Vijay Samant said his company "adopted the best business practices and made the best business decisions" in order to funnel its efforts and resources on the high-dose Allovectin-7 trial. He also explained the impetus behind dropping the low-dose, single-tumor trial of the drug in metastatic melanoma patients.
The Allovectin-7 low-dose Phase III study entailed three steps. First, an independent contract research organization collected and audited the trial's efficacy data, but kept the database secure. Second, after the FDA approved an independent endpoint assessment and adjudication committee (EAAC) that would review the final data, an independent consultant reviewed the Phase III data in the embargoed database. The consultant used a predetermined algorithm of specific statistical criteria agreed to by the FDA and Vical for evaluating the trial's progress. The third step was to be the EAAC review itself. However, based on what the independent consultant saw in that database, there will be no third step.
Allovectin-7 is an immunotherapy that is injected directly into tumors. It's a DNA/lipid complex that contains the human gene encoding HLA-B7. It is designed to cause malignant cells to express HLA-B7, and therefore trigger an immune response against tumor cells.
Samant said that although the process revealed the drug "would not meet with statistical significance the endpoints" of the trial, it does reflect a positive relationship with the FDA. He also said Vical remains enthusiastic about Allovectin-7 and "formally believes that the Allovectin-7 vaccine, with high dosing and delivery to multiple tumors," has potential. He gave numerous reasons why.
He said the low-dose, single-injection program was developed more than five years ago, and since then the company has learned that immune responses in humans appear to be DNA dose dependent. Samant said prior trials achieved response rates of up to 15 percent, but nearly 50 percent of injected tumors shrank, meaning further study in multiple tumors is validated. Allovectin-7 has a great safety profile, he said, so therefore any benefit patients receive from the drug would have a favorable risk-to-benefit ratio. And, although survival wasn't an endpoint in the Phase II trial, there was a beneficial trend in survival - 14.3 months median survival compared with historical controls of six to 11 months.
All of which means Vical will forge ahead with its Phase II high-dose, multiple-tumor trial of Allovectin-7 in metastatic melanoma. The company requested to expand enrollment up to 124 patients in the trial, which was agreed to by the FDA. In fact, with the closing of the early stage head and neck cancer trial - due to difficulty in recruiting patients, Vical said - it has just metastatic melanoma on its clinical plate.
Even Leuvectin will be used for metastatic melanoma. The company said further development of Leuvectin for kidney cancer is "not justified in light of other priorities" and said developing the product for the prostate cancer indication would "require far greater resources than we can devote independently." But even though it no longer is developing Leuvectin in the clinic, the company plans to evaluate information gleaned from Leuvectin trials for potential application in metastatic melanoma, perhaps in combination with Allovectin-7, Samant said in the call.
Samant expects to have data from the high-dose Allovectin-7 trial ready for presentation at the American Society of Clinical Oncology meeting in May. Data from the now-expanded Phase II high-dose trial will determine whether it discusses with the FDA a potential Phase III study.
Wall Street treated the news of stopping four clinical trials with kid gloves - Vical's stock (NASDAQ:VICL) fell 25 cents Thursday to close at $4.60. But with a wealth of cash - about $123 million as of June 30 - and a market capitalization of about $92 million, the company was already trading beneath cash value. It lost $5 million in the second quarter and $10.2 million for the first six months of the year.
The trend in the cash-starved biotechnology sector is cutting back and concentrating on the strongest products, with the hope of surviving the down market and coming out the other side a more robust entity. That is Vical's plan, too.
"We are focusing our resources on developing Allovectin-7 for use in patients with metastatic melanoma," Samant said, which makes Vical "a stronger company today."