The FDA approved Valeant's brodalumab for the treatment of moderate-to-severe plaque psoriasis, but with the warning that the drug is associated with suicidal ideation and behaviour.

The antibody targets the interleukin-17 (IL-17) pathway, fertile ground for drug developers. Although the drug follows on the heels of Novartis's secukinumab and Lilly's ixekizumab, which target IL-17 ligands, this is the first approval for a therapy that targets the IL-17 receptor (IL-17R). Because IL-17R binds to multiple ligands, its developers hoped that it would provide broader blockade against pathway activation and therefore benefits over the competition.

AstraZeneca and Amgen, who collaborated on the development of brodalumab, instead found a risky side effect profile. In clinical trials of the drug, 34 of 4,464 plaque psoriasis patients who received the drug experienced suicidal ideation.

The mechanistic explanation for an increased suicide risk is unknown, and other drugs that target the same pathway have not raised the same safety flag (Nat. Biotechnol. 33, 894–895; 2015). Nevertheless, these findings prompted Amgen to drop its interest in the drug in 2015. Months later, AstraZeneca licensed brodalumab to Valeant for US$100 million up front, $345 million in possible milestones and a share of any profits.

The drug now enters a competitive field. In addition to the approved IL-17 monoclonal antibodies (mAbs), there is growing interest in anti-IL-23 mAbs that act upstream in this pathway. The agency approved Johnson & Johnson (J&J)'s IL-23- and IL-12-targeting mAb ustekinumab for psoriasis in 2009. Next-generation competitors that target only IL-23 — and so do not act on the T helper 1 cell immune response — may offer an improved safety profile. J&J's IL-23-specific candidate guselkumab is under review at the FDA, and Sun Pharmaceutical Industries' tildrakizumab and AbbVie's risankizumab are in phase III.