Phase 3 Trial Points to Successful Treatment of Itch-Causing Condition — and Type 2 Inflammation as a Culprit

Dupixent (dupilumab) was the first FDA-approved treatment for adults with prurigo nodularis, a chronic skin condition characterized by severe itching and nodular lesions, or bumps in the skin. The itching is believed to come first with excessive scratching the nodular lesions. Still, the root causes of prurigo nodularis incompletely understood. Some research has pointed to a reduction of intraepidermal nerve fibers, suggesting that it could be manifestation of a form of neuropathy. But the efficacy of Dupixent argues for type 2 inflammation playing a significant role in the prurigo nodularis pathogenesis because Dupixent works by inhibiting interleukin (IL)-4 and IL-13, cytokines that figure prominently in type 2 inflammation.

Positive results from a phase 3 trial of nemolizumab as a treatment for prurigo nodularis reported last week in the New England Journal of Medicine furthers the case for type 2 inflammation being a major culprit in causing the condition, which in its most severe form can be debilitating disease as well as lead to depression and anxiety, partly because it interferes with sleep. Nemolizumab is an inhibitor of IL-31, another cytokine secreted during type 2 inflammation that interacts with nerves to cause the itching sensation. But in the discussion section of the New England Journal of Medicine article about the phase 3 results, corresponding author Christophe Piketty, M.D., Ph.D., referenced research showing that nemolizumab, by inhibiting IL-31, may also have a downstream, quelling effect on other cytokines get secreted during type 2 inflammation.

Piketty is vice president, global senior program head, for Galderma, the Swiss company that is developing nemolizumab.

The phase 3 trial, which was paid for by Galderma, showed that after a prespecified time of 16 weeks, more than half (56.3%) of the 183 patients randomized to be treated with nemolizumab experienced a substantial decline in itchiness (as measured on standardized scale) compared with approximately one-fifth (20.9%) of the 91 patients randomized to the placebo group. The treated patients were also far more likely to experience “almost complete itch relief,” a secondary end point, than the those treated with the placebo (19.7% vs. 2.2%). The treated group also fared better when it came to measurements of pain, sleep disturbance, health-related quality of life and other factors.

The results did show, though, that the 5.5% (10 of 183) of patients in the nemolizumab group experienced atopic dermatitis while none in the placebo group. Piketty and his colleagues said that most of the atopic dermatitis cases were mild and treated with topically.

The study volunteers randomized to be treated with nemolizumab, which is administered as a subcutaneous infection, were also more like to experience headache than those in the placebo group (6.6% vs. 4.4%).