Research Program Marks Milestone for Testing Future Clinical Trials in Autism Spectrum Disorder
Autism Spectrum Disorder (ASD) is one of the most common neurodevelopmental disorders, affecting approximately one in 68 children.1 ASD occurs in all racial, ethnic and socioeconomic groups and is almost five times more common amongst boys than girls.1 It is a complex area, which has made studying and finding effective therapies very difficult.
EU-AIMS (European Autism Interventions – A Multicentre Study for Developing New Medications), is a collaboration between patient organisations, academia and industry, and is the world’s largest multi-centre project funded and run under the Innovative Medicines Initiative (IMI) addressing ASD. Among the aims of this project is to develop and validate new methodologies for the advancement of novel therapies to treat ASD. The enormous diversity amongst those with ASD has now been recognized and both medical and non-medical options need to be developed that address the different needs of those with the disorder. It is therefore vital to have clearly defined biomarkers or biological measures, which identify different subtypes of ASD, to match them with the treatments most likely to provide benefit.
EU-AIMS reported in a correspondence published in Nature Reviews Drug Discovery, thatthe group, composed of academics from seven study centres, the pharmaceutical industry (including Roche, J&J and Lilly), and the European Medicine’s Agency (EMA) have come to a shared understanding of criteria and methodologies for the identification of biomarkers and additional measures for success, which is reflected by the EMA’s issuance of Letters of Support which have been made publically available on the agency’s website.
A ‘LEAP’ ahead
The EU-AIMS Longitudinal European Autism Project (LEAP) is the largest clinical observational study in the world that combines genetics, neuroimaging, cognitive testing and clinical assessments. Even if potential new compounds for ASD are found, there are still considerable challenges in testing them in clinical trials, given the lack of qualified biomarkers and the extreme heterogeneity of the ASD population. The EU-AIMS LEAP study aims to identify biomarkers for ASD that can also act as population stratifiers and potentially as endpoints in clinical trials. Stratifying patients into more homogeneous sub-populations may prove important in determining which patients may benefit from pharmaceutical interventions according to their mode of action. To further understand whether data generated in this study would be accepted in regulatory decisions for future clinical trials, advice was obtained from the EMA, the regulatory agency responsible for approving any new medicines in the European Union (EU).
Alignment for success
The EMA agreed on the importance of further developing proposed biomarkers for ASD and these will be reviewed across a broad selection of patients (such as different ages, sex, those with co-morbidities and those without). Biomarkers are a measurable component which can include: the results of brain-imaging tests that can track brain activity and connectivity, eye-tracking studies that measure attention to social cues and the analysis of biological samples, such as blood, saliva and urine. Biological samples, for example, might be used to detect genetic risk factors that may contribute to some forms of ASD.
Current clinical trials do not provide the flexibility required to properly assess how well a treatment, or other intervention, may improve deficits/symptoms in ASD, as there are a large range of variables. The EU-AIMS consortium outlined the proposed criteria for the selection of study participants in LEAP within the Nature Reviews Drug Discovery article, which included the types of symptom improvements that should be used to measure benefit and also agreed upon the methods used to identify biomarkers to help distinguish distinct subtypes of ASD.
Up to 70 percent of people with ASD have one or more co-occurring conditions and the EMA supported the inclusion of study participants with psychiatric comorbidities, such as attention-deficit hyperactivity disorder (ADHD), anxiety or depression.2 In addition, the EMA supported the inclusion of people with ASD and intellectual disability, as it is estimated to affect 55 percent of those with ASD and is especially common in those more severely affected.3
What does this mean for future trials?
The outcome of the advice process with the EMA is an important step towards a shared understanding of biomarker criteria for ASD. The validation and qualification of biomarkers will be key in progressing the clinical trials needed to assess the efficiency and mechanism of therapeutic interventions, define the patient populations that will benefit from them, and facilitate the regulatory approval of new therapies.
European Autism Interventions - A Multicentre Study for Developing New Medications (EU-AIMS)
EU-AIMS is a multi-partner public-private partnership that involves a novel collaboration between organisations representing affected individuals and their families (Autism Speaks), academia and Industry, who for the first time have come together to develop the infrastructure underpinning new treatments for autism. Patient organizations, academic and industry join forces to develop and assess novel treatment approaches for autism.
1 Autism Spectrum Disorder Facts. CDC. http://www.cdc.gov/ncbddd/autism/treatment.html (last accessed November 2015).
2 Simonoff, E. et al (2008). Psychiatric disorders in children with autism spectrum disorders: prevalence, comorbidity, and associated factors in a population-derived sample. J Am Acad Child Adolesc Psychiatry, 47, 921-9.
3 Charman, T. et al. IQ in children with autism spectrum disorders: data from the Special Needs and Autism Project (SNAP). Psychol. Med. 41, 619–627 (2011).