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VPD-737 (serlopitant) is a potent oral NK1 receptor antagonist that Tigercat Pharma, Inc., licensed from Merck in 2012. It is highly selective for the human NK1 receptor and in both animal and human testing it has been well tolerated. The pharmacokinetics have been studied in animals and humans as well as the receptor binding allowing for rational dose selection for further trials.
Beginning in 2005, Merck evaluated serlopitant in 13 Phase 1 studies and two Phase 2b studies, comprising over 900 subjects and patients. In the Phase 1 studies, single doses of 400 mg and multiple doses of 50 mg per day up to 28 days were generally well tolerated in healthy young males and in healthy elderly males and females (age ≤80 years). Merck also assessed serlopitant for safety and efficacy in a Phase 2 study in overactive bladder and in a Phase 2 study for alcohol dependence.
Although pruritus is a frequent symptom of many dermatological and systemic conditions its pathophysiology is poorly understood. Pruritus is a cutaneous sensory perception transmitted via neuropeptide-containing unmyelinated nerve fibers in the papillary dermis and epidermis. Substance P and its receptor, neurokinin receptor 1 (NK1), have been implicated by a number of preclinical and clinical studies to be important in the pathogenesis of pruritus.
Tigercat Pharma, Inc., is currently assessing VPD-737 in two Phase 2b studies. The first study, a randomized, double blind, placebo controlled study over six weeks is studying the safety and efficacy of VPD-737 in 240 patients with chronic pruritus. The study is being conducted in 24 sites within the United States and the primary endpoint is change in pruritus severity as measured by the Visual Analog Scale. Tigercat is also studying VPD-737 in a randomized, double blind, placebo controlled study over eight weeks to assess the safety and efficacy of VPD-737 in 60 patients with prurigo nodularis, a severe form of pruritus characterized by pruritic nodules and lesions. This study is being conducted in 4 sites within Germany and the primary endpoint is change in pruritus severity as measured by the Visual Analog Scale.
Prurigo Nodularis (PN) is a chronic inflammatory dermatosis of unknown etiology. It causes several to hundreds of papulonodular eruptions on a patient's skin which are intensely itchy. Patients may be driven to distraction by the itch/scratch cycle that the disease induces, as may their doctors by their inability to treat the condition effectively. The constant scratching leads to the development of discrete, excoriated, nodular, hyperpigmented/purpuric lesions with crusted or scaly surfaces.
Individuals with PN typically have a severely disturbed quality of life and are frequently unable to function effectively during everyday activities including work. Depression and anxiety are also commonly associated with persistent PN and patients typically report significant challenges sleeping. The current standard of care is corticosteroid and antihistamine therapy, however, the treatment of PN is notoriously challenging and is reflected in the number of treatments that are prescribed with poor results. Once the itch-scratch cycle becomes established, it is extremely difficult to interrupt. For those patients who do not respond to first-line treatments with antihistamines or corticosteroids, there are no safe and effective second line treatment options.
The prevalence of PN in the general population is unknown as the disease is frequently included in chronic itch disorders in epidemiological studies. The condition is, however, relatively common amongst middle-aged women who have some of the precipitating conditions (e.g., atopic dermatitis). It is thought that the prevalence of so-called neurotic excoriations, of which an unknown proportion of cases of prurigo nodularis might be a manifestation, is about 2% in dermatology clinics and 9% in those with an underlying cause for pruritus.
1. Haas S, Capellino S, Phan NQ, et al; Low density of sympathetic nerve fibers relative to substance P-positive nerve J Dermatol Sci. 2010 Jun;58(3):193-7. Epub 2010 Apr 4.
2. Grundmann S, Staender S. Chronic pruritus: clinics and treatment. Annals of dermatology. Feb 2011; 23(1):1-11
3. Scheinfeld NS, Neurotic Excoriations, Medscape, Aug 2011.