Washington Editor

Positive Phase IIb data boosted shares in Valentis Inc., which reported that its lead investigational product VLTS 934 improved patients with peripheral arterial disease.

Calling industry watchers "over-reliant on animal data," Benjamin McGraw, the company's chairman, president and CEO, told BioWorld Today that no good animal model exists in this indication. Instead, it was a previous Phase II study of a gene-based product called Deltavasc that pointed Valentis in the direction of VLTS 934, a non-ionic block copolymer known as a poloxamer that is acting as an anti-inflammatory agent.

In that trial, Deltavasc failed to differentiate itself from a control polymer in improving patients with the intermittent claudication form of peripheral arterial disease, leading the Burlingame, Calif.-based company to find that the polymer itself was causing the benefit. But investors reacted negatively, and shares in Valentis (NASDAQ:VLTS) lost two-thirds of their value, or $4.29, to close at $2.36. (See BioWorld Today, Sept. 30, 2004.)

The new favorable findings led to a reversal of sorts, with the stock gaining 90 cents Wednesday, or 37 percent, to close at $3.56.

The data were uncovered in an interim analysis conducted by independent statisticians confirming placebo group assumptions, based on a representative sample of patients receiving saline as placebo.

The trial has randomized 148 patients to receive either VLTS 934 or placebo to evaluate its effect on the same disease studied in the Deltavasc study, a condition that results from atherosclerosis in patients' legs.

The trial's primary efficacy endpoint is measuring improvements in exercise tolerance after 90 days with VLTS 934 compared to placebo.

The study is designed with an 80 percent chance of correctly identifying a statistically significant response between the treatment and placebo groups. It remains blinded, with final efficacy data scheduled for the middle of the year. There was no impact on the Type I error rate, and no adjustments are necessary to the alpha-level for the final analysis.

VLTS 934 appears to have a direct effect of repairing compromised cell membranes and reduces levels of specific mediators of inflammation: IL-6, IL-8 and MCP-1. Such a reduction in those three cytokines of inflammation would explain the improvement in blood flow and exercise tolerance seen in a Phase IIa trial that tested VLTS 934 in virtually the same patient population and followed the same dosing and assessments.

Specifically, that previous study demonstrated a 34 percent improvement in exercise tolerance (p<0.00001), as well as a statistically significant improvement in an indicator of blood flow, the ankle branchial index, compared to baseline. Also, VLTS 934-treated patients experienced an increase in work capacity of 74 percent over baseline measurements.

McGraw said peripheral arterial disease represents "an enormous market" opportunity. The only other product used in that space is Pletal (cilostazol). But it has two drawbacks, he said, as patients have difficulties with its adverse events and prescribers have trouble with its counterindication among those with heart failure. VLTS 934, on the other hand, avoids both of those drawbacks.

McGraw said he is confident in the future success of this latest study, which he noted was designed to "be considered a pivotal trial." A Phase III study, which could begin in about a year following end-of-Phase II talks with the FDA, would likely "look very much like this trial," McGraw added.

Valentis, which is working to secure a development and marketing partner by the end of this year, has sufficient funding to complete the Phase IIb trial in that time frame and would move into Phase III with or without an agreement in place. McGraw said he envisions partnering with a large pharmaceutical firm, with a worldwide presence, to advance VLTS 934 all the way to commercialization.

Contrary to the aspirations of others in the biotech space, Valentis has no designs on entering a co-marketing arrangement or developing an internal sales force. "We're a development company," McGraw said.

Other research moving forward at Valentis includes preclinical work to reformulate Deltavasc, additional studies on the angiogenic Del-1 (Developmentally regulated Endothelial cell Locus-1) gene for ischemia, and efforts to out-license an antibody to that gene, which could find use in oncology applications given its anti-angiogenic properties.