PRAGUE – In a 48-week, phase-II study of brodalumab – a novel selective interleukin-17 inhibitor – 60% of psoriasis patients achieved a Psoriasis Area and Severity Index score of 100, reported Dr. Kim A. Papp.
There were 181 patients with moderate to severe plaque psoriasis in the multicenter, open-label study, and nearly 100% achieved at least a PASI 75 response, 80% achieved at least a PASI 90 response, and 60% achieved a PASI 100, Dr. Papp said at the annual congress of the European Academy of Dermatology and Venereology. Equally important, responses were maintained through week 48, essentially undiminished, he said.
Dr. Kim A. Papp
Dr. Papp, director of research at Probity Medical Research, Waterloo, Ont., presented the results of the open-label extension of a previously published phase II, 12-week study (N. Engl. J. Med. 2012;366:1181-9). At the end of the 12-week study, participants were observed off therapy until their psoriasis relapsed, defined as a 50% loss of therapeutic benefit. At that point, they were treated with 210 mg of brodalumab administered subcutaneously every 2 weeks for 48 weeks. The peak response was achieved between weeks 8 and 12 or 16; few study dropouts occurred.
"The side effect profile was varied and included a mix of serious infections and development of atrial fibrillation and other cardiac disorders. Certainly, there were no obvious signals to suggest that we should have undue concerns going into the planned phase III program," said Dr. Papp.
Session cochair Dr. Peter van de Kerkhof was enthusiastic about the brodalumab data. "These are absolutely fabulous results. It’s really very impressive. This study gives us a lead as to where we’re going: to a new phase in biologic therapy where we get an efficacy which we couldn’t have dreamed of 10 years ago. A new bar is set," said Dr. van de Kerkhof, professor and chairman of the department of dermatology at Radboud University in Nijmegen, the Netherlands.
Brodalumab (Amgen) is a human monoclonal antibody directed against the interleukin-17A receptor as a means of quelling inflammatory cytokines. Another humanized monoclonal antibody that neutralizes interleukin-17, ixekizumab (Eli Lilly), was also the subject of a recently published, encouraging phase II study (N. Engl. J. Med. 2012;366:1190-9). Secukinumab (Novartis) is another fully-human monoclonal antibody directed against IL-17A, which has completed several successful phase II studies. These anti-IL-17 biologics are being considered as possible new therapies for other inflammatory diseases, including psoriatic arthritis and rheumatoid arthritis.
Dr. van de Kerkhof cautioned that from a safety standpoint, it will be important to scrutinize the upcoming large, definitive phase III clinical trials of these agents for evidence of an increase in infections, particularly Staphylococcus aureus and Candida albicans.
Interleukin-17A and IL-17F play roles in the normal host-immune defenses against microorganisms. Patients with genetic defects in IL-17 tend to have problems with recurrent chronic mucocutaneous candidiasis. Moreover, individuals with chronic mucocutaneous candidiasis have been shown to have antibodies to IL-17A, IL-17F, and IL-22, he noted.
The study was sponsored by Amgen. Dr. Papp reported receiving research funds from and serving as a consultant to Amgen and numerous other pharmaceutical companies. Dr. van de Kerkhof has received research funding and consultancy fees from more than a dozen pharmaceutical companies.