Encouraging Phase III findings provided a boost to Isotechnika Inc., which Wednesday reported interim data from a psoriasis study of its lead immunosuppressive drug, ISA247.
"The take-home message is that we met our endpoints for the 24-week trial after 12 weeks," Isotechnika President and Chief Operating Officer Randall Yatscoff told BioWorld Today. "It confirms that this drug has a therapeutic window."
Called the Canadian Phase III Psoriasis (SPIRIT) trial, it met all primary and secondary efficacy endpoints with minimal side effects, he noted. Those results also are expected to pave the way for partnerships on the drug, to which the Edmonton, Alberta-based company owns all psoriasis rights.
"This bodes well for a potential licensing deal," Yatscoff added. "We've been waiting to do detailed negotiations until this data came out."
But with more than C$60 million (US$51.2 million) in reserve, he said Isotechnika is in good position to move the program forward even without a partner. Yatscoff also predicted that marketing applications for ISA247, a cyclosporine analogue and therefore a calcineurin inhibitor, would be filed in 2008.
The 24-week, double-blinded study, which began late last year, included 453 patients with stable, moderate to severe plaque psoriasis.
They were randomized to three dosing groups of orally administered ISA247 (0.2 mg/kg, 0.3 mg/kg and 0.4 mg/kg) or placebo. All four groups were of equal size. (See BioWorld Today, Dec. 3, 2004.)
In the high-dose group, 48 percent of patients achieved a 75 percent reduction in their Psoriasis Area and Severity Index (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. At those two dose levels, both PASI 50 and PASI 75 scores were clinically significant compared to placebo. The mean reductions in PASI scores among high- and middle-dose patients were 62.5 percent and 44 percent, respectively.
Also, there were no clinically significant differences in mean serum creatinine and glomerular filtration rate. Incidences of treatment-related adverse events in study drug patients were similar to those receiving placebo and unrelated to dosing, though after 12 weeks of treatment, four high-dose patients and one in the middle-dose group were withdrawn due to a clinically significant effect on kidney function.
But there were no clinically significant changes noted in hypertension, cholesterol, triglycerides and infectious complications. The adverse event monitoring results in part from ISA247's action, which is the same as tacrolimus and cyclosporine, but Yatscoff called its renal impact "a fraction of what you see for cyclosporine and other drugs of this class." Concurrent with the initial Phase III trial is a carcinogenicity study in animals.
In addition to establishing a better profile for ISA247 than other calcineurin inhibitors, Isotechnika also is positioning its product against more recent entries into the psoriasis market: the biologics. Those drugs have infectious complications, Yatscoff said, and are either intravenously infused or injected subcutaneously intramuscularly, while ISA247 is delivered orally twice daily.
"With our favorable side effect profile, this has the potential to be first-line therapy," Yatscoff said. "And compared to the biologics, it's less expensive, easier to use and easier to monitor, so there are a number of advantages."
Going forward, Isotechnika expects to begin two further Phase III trials, one in the U.S. and another in Europe. Meetings with regulatory authorities on such studies would occur after the company reports full 24-week data from the trial, which Yatscoff expects to happen early next year. He added that the future studies would test a single dose, either 0.3 mg/kg or 0.4 mg/kg of ISA247, vs. placebo or comparator medications.
Beyond psoriasis, ISA247 just entered a Phase IIb study to evaluate its ability to block rejection in kidney transplant patients as part of a collaborative effort with F. Hoffmann-La Roche Ltd., of Basel, Switzerland. Elsewhere in Isotechnika's clinical pipeline is another immunosuppressive compound called TAFA93, a prodrug of the mTOR inhibitor rapamycin. Applications being studied include uses in stents, oncology and transplants.
On Wednesday, the company's stock (TSE:ISA) gained C32 cents to close at C$2.64.