One notable competitor from that table is what may turn out to be the most significant competition for ISA247 for psoriasis - the oral Pimecrolimus formulation being studied by Novartis:
AAD: Oral Pimecrolimus Effective In Treating Psoriasis
By Paula Moyer
SAN FRANCISCO, CA -- March 24, 2003 -- Oral pimecrolimus is an effective and well-tolerated treatment for moderate-to-severe chronic plaque psoriasis.
This finding was presented here at the 61st Annual Meeting of the American Academy of Dermatology, by Klaus Wolff, MD, of the dermatology department at the University of Vienna in Vienna, Austria. "In two studies we saw no adverse effects, no effects on circulating lymphocytes, and no effect on renal function," he said. "We concluded that oral pimecrolimus is safe and effective for this condition."
Topical pimecrolimus (Enbrel), an immunomodulator developed as an alternative to corticosteroids, is used in the treatment of atopic dermatitis.
Dr. Wolff noted that the topical formulation, 1% pimecrolimus, is effective and well tolerated in 3-month-old infants with atopic dermatitis. In previous research, the maximal systemic area-under-the-curve (AUC) exposure observed in children and adults with atopic dermatitis who were treated with topical pimecrolimus for three weeks was 18.8 nigh/mL. and 11.4 ML/mL, respectively.
The researchers investigated the tablet formulation (SDZ ASM 981) in two studies. One study was designed to assess the systemic version's clinical safety, tolerability, and efficacy in patients with moderate-to-severe chronic plaque psoriasis. In the other, they sought to investigate pimecrolimus's pharmacokinetic profile after multiple oral doses.
Fifty patients with moderate-to-severe chronic plaque type psoriasis were recruited to participate in the randomised, double-blinded, placebo-controlled multiple rising dose study. The investigators followed five consecutive cohorts of 10 subjects each, who were treated with oral escalating doses of pimecrolimus, ranging from 5 mg daily to 30 mg twice daily in the treatment arms; others received placebo.
Thirty seven subjects received oral pimecrolimus over 28 days. Clinical efficacy was seen in patients receiving 20 and 30 mg of pimecrolimus twice daily. In these groups, the Psoriasis Area and Severity Index (PASI) was reduced by 60% and 75% respectively. The groups' PASI reduction was 4%.
Clinical tolerability was good, the investigators found. The only relevant adverse event was a transient feeling of heat, and they documented no clinically relevant change in renal function tests, including creatinine clearance and glomellular filtration rate (GFR). No increase in blood pressure or significant effect on blood glucose were noted.
A steady state was reached after 6 to 13 days of treatment; the mean CMax and AUC 0 - 12 hours were 54.5 ng.H/mL and to 94.9 ng.H/mL respectively, after the achievement of steady-state. Dr. Wolff and colleagues found that maximum whole blood drug concentration and drug exposure were dose-proportional. They detected no further drug accumulation beyond day 13.
These findings are consistent with those pertaining to systemic exposure to pimecrolimus following application of pimecrolimus cream 1%, which showed a low systemic exposure and acceptable tolerance to the cream. The investigators found that, even when the systemic exposure was increased up to 26-fold with oral administration of pimecrolimus for 28 days at 30 mg twice daily, the drug is still well-tolerated and safe in psoriatic patients.
The studies were sponsored by Novartis Pharma AG.
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