NATURE REVIEWS | DRUG DISCOVERY – VOLUME 16 | MAY 2017 | 305
The FDA approved Regeneron and Sanofi’s first-in-class candidate dupilumab for the
treatment of moderate-to-severe eczema. T helper 2 type responses have emerged as a unifying feature of various inflammatory and allergic diseases, such as eczema and asthma. As a result, type 2 cytokines — including interleukin 4 (IL-4) and IL-13 — have come under the spotlight as promising targets for selective treatment of these indications. Dupilumab is a first-in-class monoclonal antibody (mAb) that modulates both IL-4 and IL-13 signalling; the mAb binds to the IL-4 receptor subunit alpha (IL-4Rα), which can also dimerize with a subunit of the IL-13 receptor to control IL-13 signalling (Nat. Rev. Drug Discov. 15, 35–50; 2016).
In three randomized, double-blind placebo-controlled trials of the mAb in 2,119 patients, 36–39% of patients achieved ‘clear or almost clear’ skin at 16 weeks of treatment, compared with 10–12% of patients in the control arm. Common side effects included injection site reactions, cold sores in the mouth or on the lips, and eye and eyelid inflammation. The mAb is also in phase III trials for asthma and for nasal polyposis, and in phase II trials for oesophagitis. Companies are also developing candidates that take out IL-4 and IL-13 signalling by binding to the cytokines directly. Sanofi’s first-in-class bispecific antibody SAR156597 binds to both cytokines. It is in phase II trials for idiopathic pulmonary fibrosis. AstraZeneca’s IL-13-targeting mAb tralokinumab is in phase III trial for asthma and phase II development for eczema. Other anti-IL13 mAbs that are in phase II trials include Roche’s lebrikizumab and Celgene’s RPC4046.