Neuren’s Phase 2 trial of trofinetide demonstrates significant clinical benefit in paediatric Rett syndrome

Today (22 March 2017), Neuren Pharmaceuticals announced to the Australian Stock Exchange in Melbourne that its Phase 2 trial of treatment of Rett syndrome girls aged from 5 to 15 years with trofinetide, showed that it was of benefit for them. 

Neuren’s actual announcement can be viewed by clicking on the following link


Neuren Pharmaceuticals Ltd, whose head office is located in Auckland, is a biopharmaceutical company developing drugs for treatment of brain injury and neurodegeneration. One pharmaceutical being developed by Neuren and which is being trialled as a possible treatment in Rett syndrome, is NNZ-2566 (since renamed trofinetide). This drug is a synthetic analogue of naturally occurring neuroprotective and neurotrophic molecules derived from Insulin-Like Growth Factor 1 (IGF-1).

On Christmas eve 2012, Neuren Pharmaceuticals Ltd announced in Sydney that the Food and Drug Administration (USA) had informed the company that it may proceed with the phase 2 clinical trial to assess the safety and efficacy of NNZ-2566 oral solution in adolescents and adults with Rett syndrome. That phase commenced in April 2013.

On 12 November  2014, an announcement about trial’s outcome was made by the Australian Stock Exchange (ASX) in Melbourne, its  content being restricted to a brief summary of highlights,  processes,  enrolment,  safety,  methods of assessment,  charts  and  future plans. 

In early 2015, Neuren further advised that the trial was conducted at 3 North American locations, namely, Baylor College of Medicine (Houston), the University of Alabama (Birmingham) and Gillette Children’s Specialty Healthcare (Minnesota). Fifty three Rett syndrome individuals, aged 16 to 45 years, completed the double-blind placebo-controlled  trial. Two different dose levels of NNZ-2566 were tested, one being 35 milligram (mg) per kilogram (kg) of body weight twice per day, and the other, 70 mg per kg also twice a day. Of the 6 measures used to ascertain change after treatment with the drug, 3 indicated a change for the better in those individuals receiving the higher dose. Measures of motor behaviour, impressions of improvement, and the caregiver top 3 concerns, met the criteria in place to demonstrate improvement. A brief explanation of each of these measures, follows:     

Motor behaviour – Three broad areas were defined, namely, behaviour/social, orofacial/respiratory,  and motor/physical. However, the components of each were not specified. Changes were looked for in 17 particular activities which included communication skills, eye/social contact, irritability/crying/tantrums, response to spoken words, seizures, teeth grinding, breath holding, hyperventilation, drooling and hand movement.   

Impressions of improvement – Clinicians were required to rate whether a patient’s illness had improved, worsened or remained unchanged.

Caregiver top 3 concerns – At the commencement of the trial, caregivers were asked to state what were the 3 priority concerns that they would like to see change as a result of the treatment being administered to the Rett syndrome individual that they cared for.  

Distinguished Professor Margaret Brimble, co-creator of NNZ-2566,  gave a presentation on the drug at Rett New Zealand’s bi-annual family conference which was held in Auckland in May 2014. A recording of her talk can be found by clicking on the following link which is contained on the Rett New Zealand’s website

About trofinetide  

Trofinetide is a synthetic analogue of a naturally occurring neurotrophic peptide derived from IGF-1, a growth factor produced by brain cells. In animal models, it exhibits a wide range of important effects including inhibiting neuroinflammation, normalizing the role of microglia and correcting deficits in synaptic function. Trofinetide has been developed both in intravenous and oral formulations, for a range of acute and chronic conditions. The intravenous form of trofinetide is presently being used in a Phase 2 clinical trial in patients with moderate to severe traumatic brain injury. The oral form of trofinetide is being used in the new Phase 2 trials in Rett syndrome, and Phase 2 trials in Fragile X syndrome and mild traumatic brain injury (concussion). 

28 January 2015 – Approval sought to rename NNZ-2566 as trofinetide  

Neuren Pharmaceuticals announced in Melbourne, Australia, that the World Health Organization’s (WHO) latest publication of proposed International Names for Pharmaceutical Substances (INN), includes trofinetide as the proposed INN for glycyl-2-methyl-L-prolyl-L-glutamic acid, which is currently designated by Neuren as NNZ-2566. 

16 February 2015 – Trofinetide granted Orphan Drug designation 

It was also in Melbourne that Neuren Pharmaceuticals advised that the FDA has granted Orphan Drug designation to Neuren’s drug trofinetide for treatment of Rett syndrome…….. Orphan Drug designation is a special status that the FDA may grant to a drug intended to treat a rare disease or condition. The designation qualifies the sponsor of the drug for 7 years of marketing exclusivity following marketing authorisation.

13 October 2015 – Another clinical trial (new phase 2) of trofinetide in Rett syndrome 

Neuren Pharmaceuticals announced that the International Rett Syndrome Foundation (IRSF) had made a financial commitment of up to US$1 million, to continue its support of Neuren’s clinical trials of trofinetide for the treatment of Rett syndrome.

8 December 2015 – What is involved in the 2016 clinical trial?

Sourced from the website of the International Rett Syndrome Foundation  (

The new Phase 2 trial will confirm the tolerability and safety of trofinetide in children and will be informative with respect to the planning of a single Phase 3 trial (a pivotal trial) that will include children, adolescents and adults.  It will examine higher dose levels than the first Phase 2 trial, the results of which showed trends of increasing clinical benefit with increasing dose levels.

The primary goal of the study will be to assess the tolerability and safety of the study medication in this younger population.  Additionally, Neuren will assess clinical benefit by determining change from baseline on a number of outcome measures including the clinician-completed Motor Behavior Assessment (MBA), the Clinical Global Impression Scale of Improvement and the Caregiver Top 3 Concerns assessment.  Each of these measures exhibited clinical benefit in the first study. The trial got underway in early 2016.

14 November 2016 – Neuren completes enrolment into Phase 2 trial of trofinetide in paediatric Rett syndrome

Neuren Pharmaceuticals announced that enrolment into its Phase 2 clinical trial of trofinetide in paediatric Rett syndrome had been completed.  

The trial is a randomized, double-blind, placebo-controlled Phase 2 clinical trial for girls aged 5 to 15 years with Rett syndrome.  It is being conducted at 12 sites in the United States, led by clinicians experienced in the diagnosis and treatment of Rett syndrome.  

Faster enrolment into the trial provided Neuren with the opportunity to expand it beyond the original target of 64 completing subjects, whilst still delivering top-line results in the first quarter of 2017.  In total, 82 subjects have been randomized.  62 subjects were randomized into one of four treatment groups: 50mg/kg, 100mg/kg, 200mg/kg and placebo.  A further 20 subjects have been randomized into one of two treatment groups: 200mg/kg and placebo.  The total duration of a subject’s participation in the trial, from screening through to follow-up, is eleven weeks.  To date, 55 subjects have completed the trial and only one subject has withdrawn before completion.

30 January 2017 – Neuren completes Phase trial of trofinetide in paediatric Rett syndrome

Neuren Pharmaceuticals announce that the last subject has completed its Phase 2 clinical trial of trofinetide in paediatric Rett syndrome.

Neuren remains on schedule to receive top-line results from the trial in the second half of March 2017 and soon thereafter intends to engage potential commercial partners regarding the remaining development and commercialisation of trofinetide in the major markets.

Neuren Executive Chairman Richard Treagus commented “We are grateful for the strong support of the Rett syndrome community, which has helped us to complete the expanded paediatric trial on schedule. We look forward to receiving the results and engaging with clinical experts and potential commercial partners to determine the optimum path to market trofinetide in Rett syndrome.” ……………………  

…………………… Results from two non-clinical toxicity studies of trofinetide will be required prior to initiating extended dosing in a Phase 3 trial and submitting New Drug Applications. The first toxicity study is nearing completion and the second toxicity study is scheduled to commence in mid-2017, concluding in the first half of 2018. Plans are well advanced that would  enable manufacturing to commence in the second half of 2017 in preparation for supplying a pivotal Phase 3 trial in Rett syndrome.

March 22, 2017
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RETT Syndrome Association of Australia