The identification rate of children with autism spectrum disorder (ASD) has tripled over the past two decades. While the prevalence was 1 in 150 children in 2000, it reached the rate of 1 in 44 in 2018, in the United States, according to the Centers for Disease Control and Prevention.
Some people with ASD may experience acute agitation and seizure behaviors. However, it is difficult to estimate the prevalence of acute agitation in ASD as these episodes are mostly managed at home by relatives and parents, says Adrian Adams, CEO of Impel Pharmaceuticals.
Dr Jeremy Veenstra-VanderWeele, professor of developmental neuropsychiatry at Columbia University’s Irving Medical Center, explains that agitation is seen in the minority of autistic teens, who struggle with communication. “Most people with agitation have multiple diagnoses, such as ASD, intellectual disability (ID), speech disorder, or attention deficit hyperactivity disorder (ADHD),” he says.
The inability to communicate clearly with others and express their wants and needs results in frustration, she adds.
Off-label drug options
There is no drug specifically approved for agitation associated with ASD, and other drugs approved for irritability could be used to manage agitation episodes, says Veenstra-VanderWeele.
Janssen’s Risperdal (risperidone), a second-generation antipsychotic, gained its first FDA approval for autism-related irritability for children over the age of five, in 2006. Abilify (aripiprazole), marketed by Bristol Myers Squibb and Otsuka Pharmaceuticals, it was approved in 2009 for the treatment of irritability in children aged 6-17 with ASD. Generic versions of both drugs are now available.
While they are effective in reducing agitation episodes for most people with autism, risperidone and aripiprazole have side effects like sedation, weight gain, and risk of abnormal movement, explains Veenstra-VanderWeele.
The route of administration is another obstacle as both drugs come in the form of pills or oral injections. “It’s hard to get an upset person to swallow a pill and injections are unpleasant for most people,” she says.
Nasal spray for acute treatment
Impel Pharmaceuticals is addressing this unmet need by developing a nasal spray that delivers olanzapine powder. Eli Lilly markets olanzapine under the brand name Zyprexa. Generic olanzapine is a second generation atypical antipsychotic agent that inhibits dopamine receptors and is approved for bipolar disorder and schizophrenia. Similar to risperidone and aripiprazole, olanzapine administration is limited to pills and oral injections, often in a hospital setting.
Impel’s INP-105 is designed to deliver 5 mg of olanzapine powder into the upper nasal space via the company’s Precision Olfactory Delivery (POD) technology. The device activation mechanism aims to be a more user-friendly option for administering medication in the home, says Adams.
The company recently administered the first participant in a placebo-controlled phase IIa study investigating INP-105 in 32 adolescents with ASD, ages 12-17. The study is conducted in two specialized units that see a consistent stream of teens with autism, Adams says. The results of the study are expected in the first half of next year.
However, Veenstra-VanderWeele states that a nasal spray may not yet be the ultimate solution as it could be just as threatening to the patient if they don’t understand what’s going on. “Holding someone’s head still can be as uncomfortable and dangerous as holding another body part to give it a try,” she adds.
While it may not be a solution for everyone, having different options would still be helpful. There are no nasal sprays available for shaking, nor are there any medications specifically approved for acute shaking in ASD, explains Veenstra-VanderWeele. A nasal spray might be a preferred option for some patients, especially if it works faster than an injection, which often takes effect after the agitation period ends, she says.
In a Phase I study, INP-105 demonstrated its ability to reach plasma levels twice as fast as intramuscular injection of Zyprexa and ten times faster than oral Zyprexa, according to the January 2019 press release.