Washington Editor

OrthoLogic Corp. halted a Phase IIb study of Chrysalin (TP508) early because of a lack of efficacy, causing the company's stock to tumble Wednesday.

The shares (NASDAQ:OLGC) lost 26 cents, or 16 percent, to close at $1.37.

An interim analysis from the dose-ranging trial revealed that the synthetic peptide conferred no benefit compared to placebo in shortening the time to removing wrist fracture casts, the primary efficacy endpoint.

The event is reminiscent of a Phase III setback earlier this year in which 10 mcg of Chrysalin did not demonstrate a statistically significant benefit compared to placebo in the same endpoint. That news shaved the company's stock in half to $2.64 that day. (See BioWorld Today, March 16, 2006.)

But there might still be a path forward for the Tempe, Ariz.-based company's product. Secondary findings from that Phase III study revealed that patients with extra-articular fractures - those that do not extend into the joint space - had statistically significant shorter time to radial cortical bridging, based on radiographic evidence. "The future," said Dana Shinbaum, OrthoLogic's vice president of business development, "is to discuss with the regulatory authorities in the U.S. and Europe whether we can proceed on a pathway in fracture repair that includes a radiographic primary endpoint."

He told BioWorld Today that the interim analysis results "represent neither a setback nor a step forward." Instead, he called the findings "another data point" and added that the company planned the evaluation after unblinding the aforementioned Phase III results in the first quarter. "We interrupted enrollment in the Phase IIb trial in order to avoid spending additional resources against what we believe to be an enormously challenging primary endpoint."

Individual findings of efficacy in secondary endpoints, including radiographic healing, were not seen in the interim analysis. Further, no dose-response relationship was observed, although it was not powered at this stage to detect statistically significant differences among dose cohorts.

In the prospective, double-blind, randomized study, 274 subjects were enrolled upon its interruption, and 240 were evaluable. Subjects were randomized to receive a single injection of 1, 3, 10 or 30 mcg of Chrysalin or placebo, administered into the fracture site. The study was designed to evaluate the safety and efficacy of the doses of Chrysalin on the rate of healing in adult subjects with unstable and/or displaced distal radius fractures.

Subjects were evaluated weekly for the first eight weeks after surgery, after which they were monitored at weeks 10, 12, 26 and 52. The primary efficacy endpoint measured the time to removal of all rigid immobilization used to stabilize the fracture, defined as the time elapsed between the date of fracture surgery and the first study visit at which the investigator, based on clinical and radiographic assessments of healing, removed all rigid immobilization hardware. Shinbaum said there was no way to know why the study missed its primary endpoint.

The trial met the pre-specified safety endpoint by demonstrating no significant difference in the incidence of adverse events between the Chrysalin and placebo groups.

The interim analysis will continue and any significant findings will be disclosed as appropriate, but the company will not recruit any more patients. Beyond that indication, Shinbaum said OrthoLogic remains optimistic about the product's potential in soft-tissue healing. The synthetic 23-amino acid peptide, for which the company owns exclusive worldwide rights, has been studied in diabetic foot ulcers. Plans for that program could include dose-ranging safety and efficacy studies, and also might involve one or more partners.

Other research at OrthoLogic is focused on AZX100. A 24-amino acid peptide, it is the first of a new class of compounds in the field of smooth muscle relaxation called intracellular actin relaxing molecules (ICARMs). The product, for which the company has an exclusive worldwide license, is being evaluated for vasospasm associated with subarachnoid hemorrhage, the prevention of keloid scarring and asthma.