Washington Editor

Newly unveiled positive Phase III data on ISA247 in psoriasis confirmed previous findings from the same study and are shaping Isotechnika Inc.'s plans for its lead immunosuppressive compound.

"The additional 12 weeks attest to the safety of the drug," Isotechnika President and CEO Randall Yatscoff told BioWorld Today. "There was very little change in any of the adverse events in kidney function over the last 12 weeks of the trial. So it confirms the drug is safe and efficacious."

The Edmonton, Alberta-based company noted that the 24-week study hit all primary and secondary efficacy endpoints with minimal side effects, confirming previous findings released after 12 weeks. Specifically, there were no clinically significant differences in mean serum creatinine and glomerular filtration rates observed in its four treatment groups, and there were no clinically significant changes in hypertension, cholesterol, triglycerides and infectious complications, findings that are consistent with previously released interim data. Also, the incidence of treatment-related adverse events in ISA247 patients was not different from placebo.

Establishing such safety thresholds have been paramount in developing the orally administered compound, a cyclosporine analogue that Yatscoff called "more potent and less toxic" than cyclosporine itself. The company will use the findings to help design coming studies of ISA247, with plans to file for a pivotal trial in Europe by the end of this year and register for a pivotal North American trial early next year.

In terms of efficacy, there were continued improvements in Psoriasis Area and Severity Index (PASI) scores from 12 to 24 weeks in the mid- and low-dose groups (twice daily administrations of 0.3 mg/kg and 0.2 mg/kg). The overall decrease in PASI scores for the low-, mid- and high-dose (0.4 mg/kg twice daily) groups were 41 percent, 55 percent and 70 percent, respectively. For placebo patients who converted to the middle dose at 12 weeks, the overall decrease in PASI score was 62 percent.

"There were 200 patients on that 0.3 mg/kg dose the last 12 weeks," Yatscoff noted, "and there wasn't a single patient who showed any clinically significant impairment of renal function. So that's the take-home message."

The PASI 50 scores for the mid- and high-dose groups were 56 percent and 70 percent, respectively. PASI 75 scores for the mid- and high-dose groups were 26 percent and 49 percent. Both the PASI 50 and PASI 75 scores were statistically significant compared to placebo.

Those findings mirrored interim data released two months ago, in which 48 percent of high-dose patients achieved a 75 percent reduction in their PASI score and 72 percent achieved a PASI 50 score. In the middle-dose group, 24 percent and 47 percent achieved PASI 75 and PASI 50 scores, respectively. (See BioWorld Today, Sept. 22, 2005.)

After 24 weeks, the mean decrease in glomerular filtration rate in the low-, mid- and high-dose groups was 3 percent, 2.8 percent and 6 percent, respectively, and the company said the mean percentage change wasn't clinically significant as it falls within normal analytical and physiological variation. There were no progressive changes in renal function from 12 weeks to 24 weeks in all dose groups. Patients originally receiving placebo that crossed into the mid-dose group at 12 weeks showed no change in kidney function.

Called the SPIRIT trial, the randomized, double-blinded study was conducted at 32 Canadian sites in 451 patients. Enrollment began almost a year ago. (See BioWorld Today, Dec. 3, 2004.)

Going forward, ISA247 will be compared head to head with cyclosporine in a European trial designed to support approval there. Designs for a North American study to support FDA approval are not yet determined, as the agency will await final SPIRIT data due in January.

But Yatscoff was bullish on promoting the 0.3 mg/kg dose, which he said has "no impact on kidney function." As a result, he said they might not need to test 0.4 mg/kg doses followed by tapered administrations to 0.3 mg/kg, although he noted that the higher dose shows "excellent efficacy" with just a slight increase in kidney function problems.

The company, which owns all rights to ISA247, finds itself in a good position for those interested in acquiring commercial access to the compound. "It's no secret," Yatscoff said, "we're being courted by a number of partners for North America and Europe."

As Isotechnika works to compile final SPIRIT data, it is continuing carcinogenicity studies in rats and mice that will wrap up in 2008. Those tests are the "rate-limiting factor" in ISA247's development, Yatscoff said, and the company plans to file for approval as soon as they are complete.

In addition to its psoriasis studies, Isotechnika also has tested ISA247 in a Phase IIa trial for kidney transplantation. The company also has an additional immunosuppressive compound in its pipeline, TAFA93, which is in Phase I.

On Monday, Isotechnika's stock (TSE:ISA) gained C22 cents Monday, or 11.1 percent, to close at C$2.21 (US$1.86).