Developmental Clinical Studies - Phase 1 studies on an analogue of peptide YY as a treatment for obesity

Lead Research Organisation: Imperial College London
Department Name: Dept of Medicine

Abstract

When humans eat, the bowels naturally secrete chemicals into the bloodstream which make people feel full and which stop eating. One of these chemicals is known as Peptide YY (PYY). We have previously shown that injections of human PYY reduce appetite and food intake. We have now developed a very similar chemical, Y242, as a treatment for obesity. Y242 has been tested in animals and has been shown to be safe, and to reduce their appetite. This study will test Y242 for its safety and tolerability in humans.

Technical Summary

Obesity causes 600 premature deaths per week in the UK and is a serious risk factor for cancer, diabetes and cardiovascular disease. The only licensed drug on the UK market is neither powerful nor free of side effects. In contrast, gastrointestinal bypass surgery provides sustained, major weight loss and works mainly by elevation of potent satiety gut hormones such as peptide YY3-36 NH2 (PYY3-36). Intravenous infusion of PYY3-36 significantly reduces food intake in humans. However, its effects only last for a few hours and rapid elevation causes nausea. Following a five-year development programme culminating in a DPFS-funded project, we have successfully designed a long-acting peptide analogue of PYY, named Y242. Given subcutaneously (SC), it has a profile of action of at least 72 hours in rodents without any burst release, allowing a smooth cumulation of effect. It produces a powerful inhibition of food intake, impressive weight loss in every animal model tested and no apparent behavioural side effects. Formulation of Y242 produces prolonged plasma elevation, with the possibility of weekly dosing. Under MRC DPFS funding, pre-Good Manufacturing Practice (GMP) production has been achieved and Y242 is currently undergoing formal Good Laboratory Practice (GLP) toxicology testing for Medicines and Healthcare products Regulatory Agency (MHRA) Clinical Trial Authorisation (CTA). We now seek funding through the MRC DCS scheme to establish the safety, tolerability and pharmacokinetics of Y242 in man, in a combined single ascending dose and multiple ascending dose Phase 1 clinical study.

Publications

10 25 50
 
Title Chronic subcutaneous infusion technique 
Description Established the length of time peptides were stable in a pump (8 hours) and therefore how often the pump needed changing to provide effective day time cover. 
Type Of Material Model of mechanisms or symptoms - human 
Year Produced 2018 
Provided To Others? Yes  
Impact Allows testing in man of chronically elevated natural gut hormones. 
 
Title Analogue of peptide YY 
Description Describes novel analogues of the gut hormone peptide YY. 
IP Reference WO2008003947 
Protection Patent application published
Year Protection Granted 2008
Licensed No
Impact The analogue is being developed for a Phase I trial (funded by the MRC DCS grant). This Phase I trial has commenced April 2012.
 
Title Analogue of peptide YY 
Description Analogue Y242 completed Phase I trial 2013 
Type Therapeutic Intervention - Drug
Current Stage Of Development Refinement. Clinical
Year Development Stage Completed 2013
Development Status Under active development/distribution
Clinical Trial? Yes
Impact This drug is intended as a treatment for obesity, which afflicts 20-25% of the UK population. 
URL https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-003549-17
 
Company Name ZIHIPP LTD 
Description Zihipp is committed to transforming the lives of patients with diabetes and obesity by developing safe and effective weight loss therapies that deliver the benefits of gastrointestinal surgery without the need to have an operation. 
Year Established 2012 
Impact Company has only recently been funded no impact to date ongoing work.
Website https://www.zihipp.com
 
Description BBC Horizon 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Gave interview to BBC Horizon Programme
Year(s) Of Engagement Activity 2016
 
Description Bayliss-Starling Lecture 2014 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact talk has been published in special themed issue of J Physiol

talk was well received
Year(s) Of Engagement Activity 2014
 
Description Front page article in the Telegraph 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Front page article in the Telegraph Newspaper on 4th May 2019. Headline was: "The monthly hormone jab hailed as 'most exciting' weight-loss treatment ever"
Year(s) Of Engagement Activity 2018
URL https://www.telegraph.co.uk/science/2018/05/04/hormone-jab-mimics-gastric-band-hailed-exciting-obesi...
 
Description ITV The Tonight Programme 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Gave interview to ITV's 'The Tonight Programme' discussing current research.
Year(s) Of Engagement Activity 2015
URL http://www.itv.com/news/2015-10-21/xxl-britain-tonight/
 
Description Interview for BBC Persian World Service 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Interviewed for BBC Persian World Service programme.
Year(s) Of Engagement Activity 2015
 
Description Interview of BBC Documentary "The Truth About Obesity" 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Interviewed for BBC Documentary "The Truth About Obesity". Not yet broadcast.
Year(s) Of Engagement Activity 2018
 
Description Knighthood honour for 'outstanding' obesity expert 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Media (as a channel to the public)
Results and Impact http://www.bbc.co.uk/news/health-16363464

Publicity regarding laboratory's work.
Year(s) Of Engagement Activity 2012
 
Description Plenary Lecture, Japan Endocrine Society 2019 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Gave the Plenary Lecture at the Japan Endocrine Society entitled "Gut Hormones and the Brain". This disseminated the research so that a wide range of professionals could benefit.
Year(s) Of Engagement Activity 2019