Start of Phase II study of neurokinin-1 receptor antagonist orvepitant for intense pruritus induced by epidermal growth factor receptor inhibitors
First Clinical Trial for NeRRe Therapeutics
Stevenage, UK, 23 January 2014. NeRRe Therapeutics Ltd, which is focused on the development of neurokinin (NK) receptor antagonists for a range of indications, is pleased to announce the start of a Phase II study of the novel NK-1 receptor antagonist orvepitant. The proof-of-concept study, results of which are expected in 2015, is investigating orvepitant’s effectiveness as a treatment for the intense pruritus (itch) associated with epidermal growth factor receptor inhibitor (EGFRi) anticancer therapies. The itch intensity experienced by patients can be so severe that their EGFRi dose must be reduced or the treatment withdrawn; also pruritus along with rash has a significant effect on quality of life1.
The RELIEVE-1 trial is a randomised, double-blind, placebo-controlled study to evaluate the safety, tolerability and efficacy of two daily dose levels of oral orvepitant on EGFRi-induced intense pruritus in oncology subjects. Its primary endpoint is the difference between orvepitant and placebo in reducing the intensity of pruritus over 4 weeks, as measured on a subject-recorded numerical rating scale. RELIEVE-1 is being undertaken in 15 clinical sites in Italy, with Dr Bruno Vincenzi from Università Campus Bio-Medico di Roma as lead investigator. Dr Vincenzi and his colleagues at the centre have pioneered the use NK-1 antagonists as anti-pruritics in this setting2. Chemistry, manufacturing and control support for RELIEVE-1 is being provided by Aptuit (Verona) Srl, with clinical operations assistance from the CRO Cromsource.
Dermatologic adverse events such as pruritus are a common feature of targeted anti-cancer therapies, with incidence of this symptom induced by EGFRia drugs in clinical trials ranging from 14.6% to 54.9% depending on the specific agent3. Open-label studies in patients suffering from refractory chronic pruritus have indicated that NK-1 receptor antagonism can provide rapid and highly effective relief as well as significantly improving quality of life.2,4,5,6
Dr Mike Trower, Co-founder & Chief Operating Officer of NeRRe Therapeutics said: ‘We are very pleased to announce the start of RELIEVE-1, NeRRe’s first clinical trial, in this important area of unmet medical need. There is a strong rationale and a growing body of clinical evidence supporting the potential of orvepitant as an anti-pruritic for this devastating symptom commonly associated with EGFRis. Given its known effects on mood and sleep, orvepitant may also provide additional benefits for patient well-being.’
Dr Emiliangelo Ratti, NeRRe Therapeutics Co-founder added:
‘The intense pruritus induced by EGFRis can lead to significant suffering and poor quality of life, and we believe that a treatment for this troubling side effect would be welcomed by cancer patients and supportive care doctors alike. A successful study of orvepitant in this indication would provide further evidence of the broad therapeutic potential of the NK-1 receptor antagonist mechanism which NeRRe is exploiting in its pipeline.’
a This includes monoclonal antibodies that target the extracellular domain of EFGR, small molecule tyrosine kinase (TK) inhibitors, and small molecule dual TK inhibitors.
For more information about NeRRe Therapeutics, please contact:
Dr Mike Trower, Chief Operating Officer
Tel: +44 (0) 1438 906960
About NeRRe Therapeutics
NeRRe Therapeutics was formed in December 2012 and is focussed on the development of a portfolio of NK receptor antagonists acquired from GlaxoSmithKline (GSK), which have therapeutic potential in a broad range of indications. NeRRe Therapeutics was co-founded by Drs Emiliangelo Ratti and Mike Trower, both of whom are both former senior leaders of neurosciences drug discovery at GSK with intimate knowledge of the transferred assets and the neurokinin receptor system field. In 2012 NeRRe Therapeutics raised £11.5 million ($18.4 million) in Series A financing from two leading European financial institutions, Novo A/S (www.novo.dk/ventures) and Advent Life Sciences (www.adventventures.com), who are represented by Dr Martin Edwards (Chairman) and Dr Kaasim Mahmood respectively on the company’s Board.
Orvepitant is a ‘novel generation’ brain penetrant, selective and potent, small molecule NK-1 receptor antagonist7 that features high receptor occupancy and full and long lasting (≥24hrs) central NK-1 receptor occupancy8. It has previously completed extensive safety and toxicology studies to support its clinical development; and it has already demonstrated a positive antidepressant effect in a Phase II clinical study together with beneficial effects on sleep8.
1. Rosen AC et al. Am J Clin Dermatol. (2013), 14(4):327-33
2. Santini D et al. Lancet Oncol. (2012), 13(10):1020-4
3. Ensslin CJ et al. J Am Acad Dermatol. (2013), 69(5):708-20
4. Duval A, Dubertret L. N Engl J Med. (2009), 1;361(14):1415-6
5. Ständer S et al. PLoS One. (2010), 5(6):e10968
6. Torres T et al. J Am Acad Dermatol. (2012), 66(1):e14-5
7. Di Fabio R et al. Bioorg Med Chem. (2013), 21(21):6264-73
8. Ratti E et al. J Psychopharmacol. (2013), 27(5):424-34