Menlo Therapeutics announced top line results from two Phase 3 trials, MTI-105 and MTI-106, evaluating the safety and efficacy of once daily oral serlopitant for the treatment of pruritus (itch) associated with prurigo nodularis (PN). Neither study MTI-105 or Study MTI-106 met their respective primary endpoint a statistically significant reduction in pruritus in patients treated with serlopitant compared to placebo based upon a 4-point improvement responder analysis. The company plans to thoroughly analyze these data but does not intend to further pursue the development of serlopitant.
Study MTI-105 and enrolled 285 patients in the US and Study MTI-106 enrolled a total of 295 patients from Germany, Poland and Austria. Patients were randomized 1:1 to either serlopitant 5mg or placebo treatment. In study MTI-105, 26.45% of patients in the serlopitant group achieved a 4-point or greater improvement on the worst-itch numeric rating scale, or WI-NRS, at week 10 compared to baseline (primary efficacy endpoint) vs. 20.31% of patients treated with placebo. In study MTI-106, 25.90% of patients in the serlopitant group achieved a 4-point or greater improvement on the WI-NRS at week 10 compared to baseline (primary efficacy endpoint) vs. 18.95% of patients treated with placebo.
In February of 2020, Menlo reported Serlopitant failed to meet the primary endpoint in a phase 2 trial in patients with chronic pruritus (itch) of unknown origin.
Serlopitant is a small molecule, highly selective neurokinin-1 receptor (NK1-R) antagonist. NK1-R is one of two receptors (the other is Substance P or SP), that are critical mediators of the urge to scratch. NK1-R is a naturally occurring peptide in the tachykinin neuropeptide family. Tachykinins have numerous functions in the nervous and immune systems.
About prurigo nodularisPrurigo nodularis is a skin disease that causes hard, itchy lumps (nodules) to form on the skin. The itching (pruritus) can be intense, causing people to scratch themselves to the point of bleeding or pain. Scratching can cause more skin lesions to appear. The itching is worsened by heat, sweating, or irritation from clothing. In some cases, people with PN have a history of other diseases including eczema (atopic dermatitis), lymphoma, HIV infection, severe anemia, or kidney disease. The exact cause of PN is unknown. Although scratching is known to cause more nodules to appear, it is unclear what causes the itching to develop in the first place. Diagnosis of the disease is based on observing signs such as extremely itchy skin with the formation of nodules. In some cases, a skin biopsy is used to confirm the diagnosis. Treatment may include corticosteroid creams, oral medications, cryotherapy, or photochemotherapy.