Recruitment underway for atopic dermatitis serlopitant trial

October 13, 2017

Early trial results show a significant reduction of itch with the oral NK-1 antagonist serlopitant

An investigational treatment that inhibits a receptor implicated in itch may hold promise for treatment of chronic pruritus, recent data suggest.

Serlopitant, an oral neurokinin 1 (NK-1) receptor antagonist, has been evaluated in two trials that met their primary endpoints, according to investigators. Now, recruitment is underway for a randomized, double-blind, placebo-controlled study of serlopitant for treatment of pruritus in atopic dermatitis.

In some of the most recent data on serlopitant, presented at the 26th European Academy of Dermatology and Venereology (EADV) Congress recently held in Geneva, patients randomized to receive the oral NK-1 antagonist had a statistically significant change in pruritus score as compared with placebo.

“We have no approved treatment for chronic pruritus,” said investigator Sonja Ständer, M.D., head of the Center for Chronic Pruritus of the University Hospital Münster, Germany. “So this study is giving hope that in the future, we will have a safe and effective treatment for severely affected patients.”

SIGNIFICANT REDUCTION IN ITCH

The multi-center study, conducted at 25 sites in the United States, included 257 patients with severe pruritus as determined by a visual analog scale (VAS) pruritus score of at least seven on a scale of 1 to 10. They were randomized to six weeks of treatment with oral, once-daily serlopitant, given at doses of 0.25 mg, 1 mg, or 5 mg, or placebo.

The reduction in pruritus for serlopitant 1 or 5 mg vs placebo was statistically significant at weeks 4, 5, and 6 (P < 0.05), Dr. Ständer reported. Mean reduction in VAS pruritus scores from baseline to 6 weeks was 41.4% and 42.5% in the serlopitant 1 mg and 5 mg groups, respectively, compared with 28.3% in the placebo group.

In post-hoc analysis, investigators found that the reduction in pruritus score for serlopitant 1 mg and 5 mg vs placebo was significant by day 3 of treatment (P < 0.05). Serlopitant was well tolerated, they reported, with treatment-emergent side effects that were primarily mild to moderate in severity.

This particular study allowed chronic pruritus of any type as a “proof of principle,” and about 30% of patients enrolled had atopic disposition, Dr. Ständer said in an interview with Dermatology Times.

NEXT:  A role in prurigo nodularis?

 

A ROLE IN PRURIGO NODULARIS?

In a separate, 127-patient study, which Dr. Sonja Ständer presented earlier in 2017 at the annual meeting of the American Academy of Dermatology, serlopitant yielded a significant reduction in pruritus vs placebo in patients with prurigo nodularis.

In the study, conducted at 15 sites in Germany, patients with a VAS pruritus score of 7 or higher were randomized to receive serlopitant 5 mg once daily or placebo for 8 weeks. At the end of that treatment period, there was a 48% reduction in average pruritus severity for the serlopitant group, versus 26% for placebo (P < 0.001).

Investigators also found a significant difference between arms in favor of the serlopitant group at Week 2 and Week 4 evaluations. Adverse events were primarily mild to moderate for serlopitant in this study, with a safety profile comparable to placebo, according to investigators.

Because there are no approved treatments for prurigo nodularis, the severe itching experienced by some patients represents an important unmet need, according to Dr. Ständer.

ATOPIC DERMATITIS AT THE FOREFRONT

The currently enrolling trial of serlopitant in atopic dermatitis will include 450 patients randomized to daily high-dose serlopitant, low-dose serlopitant, or placebo, with a primary outcome measure of itch intensity on the Numeric Rating Scale (NRS) after 6 weeks of treatment. Patients must be 13 or older and have a diagnosis of atopic dermatitis.

Being able to block the NK-1 receptor is part of the rationale for evaluating serlopitant in atopic dermatitis and other conditions associated with severe itch. According to Dr. Ständer, interactions between substance P and the NK-1 receptor play an important role in pruritus pathogenesis.

Serlopitant is not the first NK-1 antagonist to be considered as an anti-itch treatment. Aprepitant, an NK-1 receptor antagonist approved for nausea and vomiting related to chemotherapy, has also been evaluated as an anti-itch treatment in conditions including atopic diathesis, prurigo nodularis, and Sézary syndrome. While aprepitant demonstrated promising anti-itch efficacy, Dr. Ständer said its use in this capacity could possibly be limited due to potential drug-drug interactions associated with the treatment.

Dr. Ständer said that due to potential concerns regarding drug-drug interactions, she would not consider aprepitant as a long-term treatment option: “Serlopitant is more proper for long-term to use in patients with chronic pruritus,” she said. “Patients with the chronic itch may need a long term treatment for several weeks or months.”

NEXT:  In summary

 

IN SUMMARY

  • Serlopitant, an oral neurokinin 1 (NK-1) receptor antagonist under clinical investigation, may be a promising treatment for severe pruritus.

  • The treatment has been evaluated as a once-daily oral treatment in 2 trials that met their primary endpoints of reducing pruritus scores vs placebo.

  • Recruitment is underway for a randomized, double-blind, placebo-controlled study of serlopitant for treatment of pruritus in adults and adolescents with a diagnosis of atopic dermatitis.

 

 

DISCLOSURES:

Dr. Ständer reports she is a member of the scientific advisory board for Menlo Therapeutics.