Dr. Papp

According to one researcher, the search may be over, as a new experimental drug called ISA247 bears a world of promise in the treatment of plaque-type psoriasis.

ISA247 (Isotechnika Inc.) is an analogue of cyclosporine, and researchers say it offers most of the benefits of cyclosporine without any of the dangerous side effects, such as nephrotoxicity.

"This change in compound configuration gives ISA247 its higher binding affinity, as well as produces fewer byproducts compared to cyclosporine.

"This is likely what accounts for the better tolerability profile in patients," says Kim A. Papp, M.D., a dermatologist at Probity Medical Research, Waterloo, Ontario.

Dr. Papp and colleagues conducted a 12-week phase 3 clinical trial in 451 patients, ages 18 to 65, with plaque-type psoriasis affecting at least 10 percent of the body.

Study participants were randomized to either receive placebo (115 patients) or ISA247 dosed at 0.2, 0.3 or 0.4 mg/kg (107, 113 and 116 patients, respectively), orally twice a day.

Results showed that at 12 weeks, a Psoriasis Area and Severity Index (PASI) 75 score was achieved in 16, 25 and 47 percent of patients in the 0.2, 0.3 and 0.4 mg/kg dosed groups, and in 4 percent of the patients in the placebo group (the highest dose providing the best efficacy).

Dr. Papp says the efficacy of ISA247 was maintained during 24 weeks. Completely disease-free patients varied and ranged from two to 12 weeks.

At the 24 week follow-up, Dr. Papp says that few of the patients exhibited changes in renal function, an increase in serum creatinine concentration or a decrease in glomerular filtration rates.

"For most compounds, it is almost impossible to get a linear relation regarding dose and effect of a drug, and in the case of cyclosporine or other calcineurin inhibitors, you get a scattergram — patients who seem to respond only at high doses or only at low doses, as well as everything in between these two extremes.

"We found a very unique linear relationship between the ISA247 drug dose and its clinical response. This may open the door in the near future for an accurate therapeutic dosage with little to no side effects of the drug.

"Another advantage of having this very linear relationship is that it may be possible in the future to find a working dosage of one capsule a day. This still needs to be investigated," Dr. Papp tells Dermatology Times.

He says that the linear response seen is likely due to the lower production of metabolites and the fact that these metabolites have minimal or no activity in terms of the clinical response, whereas in cyclosporine therapy, the metabolites are present in higher quantities than the drug itself, and many of these metabolites have an impact on clinical response.

According to Dr. Papp, the biologics are very useful tools; however, their biggest impediment is their high cost.

Methotrexate was once seen as a gold-standard treatment, but recent data shows that it is not nearly as effective or tolerated as once hoped.

Cyclosporine is very effective; however, it is fraught with side effects related to its high toxicity.

"ISA247 proves to be a safe and effective treatment of moderate to severe chronic plaque psoriasis.

"If the drug were to be properly dosed and managed, and it sustains its relatively low toxicity profile, it could very well become the gold standard for this type of psoriasis," Dr. Papp says.