Can a nasal spray deal with agitation in autism?

The rate at which children are identified with autism spectrum disorder (ASD) has tripled over the past two decades. While the prevalence was 1 in 150 children in 2000, it reached a level of 1 in 44 in 2018 in the US, according to the Centers for Disease Control and Prevention.

Some people with ASD may experience extreme agitation and crisis behavior. However, it is difficult to estimate the prevalence of acute agitation in ASD because these episodes are mostly managed at home by relatives and parents, says Adrian Adams, CEO of Impel Pharmaceuticals.

Dr. Jeremy Veenstra-VanderWiel, a professor of developmental neuropsychiatry at Columbia University Medical Center in Irving, explains that agitation is seen in a minority of autistic teenagers who struggle with communication. “Most people with agitation have multiple diagnoses, such as ASD, intellectual disability (ID), language disorder, or attention deficit hyperactivity disorder (ADHD),” he says.

The inability to communicate clearly with others and express their wants and needs leads to frustration, he adds.

Off-label drug options

There is no specific medication approved for agitation associated with ASD, and other medications approved for irritability can be used to manage episodes of agitation, Veenstra-VanderWeele says.

Janssen’s Risperdal (risperidone), a second-generation antipsychotic, received its first FDA approval for autism-related irritability in children over the age of five in 2006. Abilify (aripiprazole), marketed by Bristol Myers Squibb and Otsuka Pharmaceuticals, was approved in 2006 2009 to treat irritability in children six to 17 years of age with ASD. Generic versions of both drugs are now available.

Although effective in reducing episodes of agitation in most people with autism, risperidone and aripiprazole have side effects such as sedation, weight gain and the risk of abnormal movements, Veenstra-VanderWeele explains.

The route of administration is another hurdle, as both drugs are available as oral pills or injections. “It’s a challenge to get an excited person to swallow a pill, and injections are unpleasant for most people,” he says.

Nasal spray for the treatment of acute

Impel Pharmaceuticals is addressing this unmet need by developing a nasal spray that delivers powdered olanzapine. Eli Lilly markets olanzapine under the brand name Zyprexa. Generic olanzapine is a second-generation atypical antipsychotic that inhibits dopamine receptors and is approved for bipolar disorder and schizophrenia. Like risperidone and aripiprazole, the use of olanzapine is limited to oral pills and injections, often in a hospital setting.

Impel’s INP-105 is designed to administer 5 mg of olanzapine powder to the top of the nose via the company’s Precision Olfactory Delivery (POD) technology. The device’s trigger mechanism is intended to be a more user-friendly option for administering medication in a home setting, Adams says.

The company recently dosed the first participant in a phase IIa placebo-controlled study investigating INP-105 in 32 adolescents with ASD between the ages of 12 and 17 years. The study was conducted in two specialist units that see a steady stream of adolescents with autism, Adams says. The results of the study are expected in the first half of next year.

However, Veenstra-VanderWeele says the nasal spray still may not be the best solution, as it can be just as threatening to the patient if they don’t understand what’s going on. “Holding someone’s head still can be just as uncomfortable and dangerous as holding another body part to take a shot,” he adds.

While it may not be a solution for everyone, having a variety of options would still be helpful. There are no nasal sprays for agitation, nor are there medications specifically approved for acute agitation in ASD, Veenstra-VanderWeele explains. A nasal spray may be a preferred option for some patients, especially if it works faster than an injection, which often takes effect after the arousal period ends, he says.

In a Phase I trial, 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 a January 2019 press release.

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