Rationale and Early Clinical Data on IL-17 Blockade in Psoriasis

Steven M Nwe; Amanda H Champlain; Kenneth B Gordon

Disclosures

Expert Rev Clin Immunol. 2013;9(7):677-682. 

In This Article

Brodalumab

Brodalumab is a human, monoclonal antibody administered by subcutaneous injection that targets the IL-17 receptor (IL-17RA) and subsequently inhibits binding of several IL-17 cytokines including IL-17A, IL-17C, IL-17F, IL17 E and IL-17A/F. In its initial Phase I, proof-of-concept trial, 700 mg of brodalumab was administered to ten subjects who showed a clinically significant improvement after 6 weeks.[59] This was also accompanied by improvement in several histopathogical variables.

Following the positive results, a Phase II, randomized, double-blind, placebo-controlled, dose-ranging study was performed on 198 patients with moderate-to-severe plaque psoriasis, of whom 188 completed the 16-week evaluation.[60] Subjects were randomized to either placebo, every other week dosing at 70, 140 or 210 mg or 280 mg monthly. The primary end point was percentage improvement in PASI scores at 12 weeks.

Efficacy data at 12 weeks showed that mean PASI scores improved by 16, 45, 85.9, 86.3 and 76% in the placebo, 70, 140, 210 and 280 mg groups, respectively. All treatment groups showed a statistically significant improvement in PASI scores at 12 weeks, with clinically visible improvement seen as early at 2 weeks. Of particular importance, very high-level responses, including 90 and 100% improvements in PASI (100% improvement is complete clearance of disease) were found in well over half of the study subjects at the higher-dose groups. This frequency of high-level responses has not previously been seen with psoriasis therapy. During the trial, the most common reported adverse events were upper respiratory tract infection, arthralgia, nasopharyngitis and injection site reactions. Only one subject receiving brodalumab withdrew reportedly for mild urticaria. There were additionally two cases of asymptomatic grade 3 neutropenia (i.e., 500 to <1000 cells per cubic millimeter), both of which resolved with discontinuation of the drug. Currently, a Phase III development program for brodalumab is active.

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