Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterised by varying social and communication impairments and pervasive repetitive behaviours. It is a highly heterogeneous disorder with a wide range of associated non-core symptoms and severities. While there are many different treatment options used to target the variety of associated symptoms, the majority of these are prescribed off-label, resulting in significant opportunity for developers in the ASD market.

Last month, 117 high-prescribing psychiatrists, paediatricians and primary care physicians from the seven major markets (7MM: US, France, Germany, Italy, Spain, UK and Japan) were surveyed on the current trends in the treatment of ASD, including key unmet needs. Needs for treatment options to target irritability and aggression associated with ASD, the core symptoms of ASD, and severe behaviour problems associated with ASD were consistently ranked by respondents as the most important in the ASD market (ranging from one to nine, where one indicated the most significant need and nine the least important). This trend was seen throughout the 7MM. Figure 1 shows the average ranking from the 117 respondents.

Of the symptoms associated with ASD, key opinion leaders (KOLs) interviewed by GlobalData agreed that irritability and aggression were the most common symptoms that patients and/or their caregivers were likely to seek treatment for. Although there are two treatments for irritability associated with ASD approved by the FDA, Johnson & Johnson’s Risperdal (risperidone) and Otsuka Pharmaceutical’s Abilify (aripiprazole), these atypical antipsychotics are associated with undesirable side effects such as weight gain, and KOLs are reluctant to prescribe them in young children. As such, significant opportunity remains for treatment options with improved safety profiles as well as good efficacy.

To this end, Otsuka and AbbVie are investigating their second-generation atypical antipsychotic products, Rexulti (brexpiprazole) and Vraylar (cariprazine), respectively, in ASD. In addition, there are several novel mechanisms of action being trialled as alternatives to the atypical antipsychotic class, including Jazz Pharmaceuticals’ cannabinoid receptor 1 agonist GWP-42006 (cannabidivarin) and Axial Therapeutics’s gut-restricted molecular therapy AB-2004. Of these novel options, KOLs believed AB-2004 in particular to be a promising alternative to the atypical antipsychotics for irritability.

There are three core symptoms of ASD, whereby the patient exhibits social impairments, communication impairments and repetitive behaviours. There are currently no approved therapies to target these core symptoms and, therefore, each of these symptoms individually constitutes an unmet need for therapeutic intervention, warranting targeted drug development.

KOLs interviewed by GlobalData also identified the lack of treatment options for core symptoms as the primary and most significant unmet need for ASD patients. There are several novel pipeline products aiming to overcome this particular unmet need. These include Johnson & Johnson’s fatty acid amide hydrolase inhibitor JNJ-5279, Yamo Pharmaceuticals’ tyrosine 3 monooxygenase inhibitor metyrosine, and Paxmedica’s purinergic receptor P2X and P2Y antagonist PAX-101 (suramin hexasodium). These products are all yet to progress to Phase III clinical trials, so it will be several years before any therapies targeting the core symptoms could enter the market; however, KOLs highlighted JNJ-5279 as particularly interesting.

The third unmet need highlighted by the survey is for treatments for severe behavioural problems associated with ASD. With no treatments available specifically for this, and only one product in the late-stage pipeline, Jazz Pharmaceuticals’ Epidiolex (cannabidiol), the need for treatments for severe behavioural problems associated with ASD is likely to remain unmet. Many of the KOLs interviewed by GlobalData reported anecdotal positive opinions from patients on the use of cannabis to improve various symptoms associated with ASD and so were pleased to see Epidiolex being investigated in clinical trials.

Any novel products for the treatment of symptoms associated with ASD will have to demonstrate significantly improved efficacy and/or safety in order to displace the widely available cheap generic therapies currently used, such as atypical antipsychotics, antidepressants and stimulants. In contrast, GlobalData expects that any products developed for the core symptoms of ASD, for which there are no treatments available, would likely see strong uptake and could dramatically alter the ASD market.