Isotechnika Inc. reported positive final data from a Phase II psoriasis study of its immunosuppressive candidate, ISA247.
The Edmonton, Alberta-based firm said ISA247, a compound being developed in partnership with F. Hoffmann-La Roche Ltd., met or exceeded all primary and secondary efficacy and safety endpoints in patients with moderate to severe psoriasis.
"There is no reason to expect that Phase III should be anything but smooth sailing," Isotechnika Chairman and CEO Robert Foster told BioWorld Today. "But because of our partnership with Roche, we have to go to the next step - to sit down with them in a joint development committee and a joint steering committee. We'll timetable things in those two committees."
He said final details regarding manufacturing processes would further dictate a timeline, but added that recruitment should begin in about a year. Foster also optimistically predicted market approval for the drug in the next three to four years.
But at the moment, the 10-year-old company is promoting the recent success of its latest-stage product.
In the high-dose arm of the double-blinded, placebo-controlled study, data showed that more than half the patients reached the primary efficacy endpoint - a two-point reduction of Static Global Assessment scores from baseline. Specifically, findings showed 54 percent achieved the parameter, compared to 17 percent in the low-dose group and none in the placebo group (p<0.0001).
Isotechnika said efficacy results showed no significant adverse effect on blood pressure and lipid levels - mean serum creatinine levels remained within the acceptable reference range indicating normal kidney function was maintained for all dosing groups. No significant adverse events were recorded.
Nearly three-quarters of the 201 patients achieved the secondary endpoint: a 75 percent reduction in the Psoriasis Area and Severity Index (PASI) patient scores from baseline. In the high-dose arm, data showed that 74 percent achieved this parameter, compared to 18 percent for the low-dose group and none in the placebo group (p<0.0001). A 50 percent reduction in PASI scores was observed in 88 percent of high-dose patients and 40 percent of low-dose patients.
The 12-week study was randomized to a ratio of two patients receiving a high dose of ISA247 (0.75 mg/kg) twice a day, two patients receiving a low dose of the calcineurin inhibitor (0.25 mg/kg) twice a day and one patient on placebo. At the end of the study, which was carried out at 12 Canadian centers, patients were monitored for an additional six weeks.
Isotechnika said earlier studies indicated that ISA247 is more potent and less toxic compared to other immunosuppressants in its class, such as cyclosporin A. Foster pointed to a combination of its safety profile and efficacy as advantageous in treating psoriasis, which in 2001 resulted in drug sales estimated at $600 million, according to Isotechnika.
"Knowing that our drug is a cyclosporin analogue, we thought it should work but going into the trial we weren't sure about toxicity issues," he said. "We maintained kidney function within normal parameters, and downstream from the kidney is blood pressure and that remained normal. And the patients cleared up."
In terms of PASI score improvement, Foster said ISA247 performed better than biologic treatments being studied in psoriasis, including Enbrel (etanercept, from Amgen Inc.) and Remicade (infliximab, from Johnson & Johnson), as well as Amevive (alefacept, from Biogen Inc.), which was approved by the FDA last month but turned down weeks later in Europe. (See BioWorld Today, Feb. 21, 2003.)
The drug, which also is in Phase II development as immunosuppressive therapy in organ transplantation, was partnered last spring with Basel, Switzerland-based Roche in a deal that could garner up to $215 million for Isotechnika. Roche is responsible for 70 percent of the shared development costs of ISA247 and will pay Isotechnika license fees as well as, potentially, development and commercial milestones. Roche also made an equity investment in the company. If ISA247 is commercialized, Isotechnika also would receive undisclosed royalties at escalating rates. (See BioWorld Today, April 10, 2002.)
Phase II studies have wrapped up in renal transplantation patients, though Foster said results continue to be analyzed. He said data from the randomized, three-month, 130-patient study, which compared cyclosporin to ISA247 in patients that had been treated beforehand with cyclosporin for at least six months, showed that the investigational drug stabilized renal function. ISA247 will be studied next in newly transplanted kidney patients that have not been exposed to cyclosporin.
The drug also is expected to be studied in liver transplantation patients. A month after Isotechnika reported the development partnership, the companies decided to stay a planned Phase II trial in rheumatoid arthritis and instead focus on ongoing development in psoriasis and renal transplantation. (See BioWorld Today, May 13, 2002.)
Beyond ISA247, Isotechnika is developing a number of research-stage pipeline programs focused on analogues that could be used in combination with existing drugs.
"We have some molecules we are testing for gastrointestinal toxicity and drug absorption," Foster said.
Isotechnika's shares (TSX:ISA) dipped C2 cents Monday to close at C$3.03 (US$2.07).