Maureen Salamon

September 15, 2017

GENEVA — Serlopitant, an investigational agent that blocks the sensation of itch in the brain, might offer hope to patients whose lives are consumed by an endless desire to scratch, according to results from the first clinical trial that specifically included patients with chronic pruritus of any type.

"This seems to be a very promising approach," said investigator Sonja Ständer, MD, from Universität Münster in Germany. "The drug was active from the first days, which is desired by patients who want to have something that's very quickly active."

The study was open to any patient with chronic pruritus, "just to show that serlopitant works. And I think it does," she told Medscape Medical News.

Many patients have diseases on top of severe pruritus. The top three conditions that cause chronic itch are prurigo nodularis, atopic dermatitis, and chronic kidney disease, but a wide spectrum of diseases, such as HIV, liver disease, and lymphoma, are characterized by pruritus.

Intense itch can affect quality of life to a level comparable to chronic pain, and is linked to disrupted sleep, anxiety, depression, and suicidal ideation, Dr Ständer explained.

There is no drug specifically designed to treat chronic pruritus — regardless of disease origin — approved by the US Food and Drug Administration (FDA). Current therapies, such as antihistamines and topical corticosteroids, provide inadequate itch relief or are associated with safety or tolerability issues, she pointed out.

These data show that the drug really targets the nerve fibers to stop signaling the itch to the brain.

Interaction between the neuropeptide substance P and its receptor, the neurokinin 1 receptor (NK1R), is pivotal in the pathogenesis of chronic itch, she explained. Serlopitant, a highly potent small-molecule NK1R antagonist, disrupts the itch signal in the skin and does not let it pass to the brain.

"These data show that the drug really targets the nerve fibers to stop signaling the itch to the brain." When inflammation is targeted, it takes longer to "stop the cascade," Dr Ständer said here at the 26th European Academy of Dermatology and Venereology Congress, where she presented results from the phase 2 multicenter trial.

The investigators randomized 257 patients 18 to 65 years of age to a 6-week course of once-daily oral serlopitant at doses of 0.25 mg, 1 mg, or 5 mg, or to placebo.

At 4, 5, and 6 weeks, changes in baseline visual analog scale (VAS) itch scores were significantly greater in the 1 mg and 5 mg serlopitant groups than in the placebo group (P < 0.5).

Study participants had experienced chronic itch for at least 6 weeks that was unresponsive to topical steroids or antihistamines. Baseline VAS itch scores were at least 7, indicating intense itch.

By week 4, the majority of patients in the serlopitant groups had either mild or no itching, whereas only 40.4% of the placebo group did. By week 6, nearly 72% of patients in the 1 mg serlopitant group had mild or no itching, compared with 50% in the placebo group.

Approximately one-third of patients in the serlopitant groups experienced treatment-emergent adverse events, but the vast majority were mild or moderate, Dr Ständer reported. Common adverse effects included dizziness, diarrhea, and headache.

Serlopitant could well become the first FDA-approved drug specifically for chronic itch, she said. It might also work against acute itch, but studies to determine that will have to be conducted.

Dr Ständer said that she will be involved in phase 3 trials of serlopitant for chronic pruritus. "This is something like a headline for my professional life: We need convincingly effective drugs for chronic pruritus," she said.

Marcis Septe, MD, a dermatologist in private practice in Ventspils, Latvia, said he hopes that the robust anti-itch effects of serlopitant persist in later-stage clinical trials so his patients can benefit.

"A lot of patients suffer for many years with nocturnal itch and scratching, and it's difficult for patients and dermatologists," he told Medscape Medical News. "I think clinical trials need to go faster from phase 2 to phase 3, and if it's good enough at phase 3, it means my patients can get it."

The next big question is how much serlopitant would cost if it does enter the market. About half of all inflammatory diseases include chronic itch, so the demand would be great, he added.

"There are a lot of agents against psoriasis, but not everyone can buy them," Dr Septe said. "But these patients with chronic itch are suffering more than patients with psoriasis."

Funding for this research was provided by Menlo Therapeutics Inc. Dr Ständer is an investigator for Dermasence, Menlo Therapeutics, Trevi Therapeutics, and Vanda Pharmaceuticals; an advisor for Almirall, Astellas, Beiersdorf, Celgene, Chugal Pharma, Creabilis, Daiichi Sankyo, Galderma, Helsinn, Kiniska, Kneipp, Maruho, Merz, Nerre, Novartis, Pierre Fabre, Sienna, and Ziarco; and receives personal fees from Almirall, Astellas, Beiersdorf, Celgene, Chugai Pharma, Creabilis, Daiichi Sankyo, Galderma, Helsinn, Kiniska, Kneipp, Maruho, Menlo Therapeutics, Merz, Nerre, Novartis, Pierre Fabre, Sienna, and Ziarco. Dr Septe is an investigator for Novartis and Baxalta.

26th European Academy of Dermatology and Venereology (EADV) Congress: Abstract FC04.09. Presented September 14, 2017.

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