Low-dose PAX-101 improves autism spectrum disorder symptoms in boys
Click Here to Manage Email Alerts
Boys with autism spectrum disorder who received 10 mg/kg of a suramin IV infusion known as PAX-101 experienced greater improvements in symptoms than those who received 20 mg/kg of the same treatment or placebo, data show.
According to the CDC, one in 54 children in the U.S. had ASD in 2016, up from one in 150 children in 2000. ASD is more than four times more common in boys than girls.
PAX-101 (suramin IV, PaxMedica) is an antipurinergic therapy delivered once monthly via an IV infusion, according to the manufacturer. The therapy appears to reverse the effects of mitochondrial dysfunction, which has been hypothesized to be the cause of autism spectrum disorder symptoms, via purinergic receptor blockade. It may lower the amount of neuroinflammation in children, the manufacturer said.
“There is an important unmet medical need to find new medicines that will address the core symptoms of the disorder,” David Hough, MD, chief medical officer of PaxMedica, told Healio Primary Care. “There are approved medicines which address irritability associated with autism, but nothing to address issues with social communication, repetitive behaviors or difficulty establishing relationships.”
Hough and colleagues randomly assigned 52 boys aged 4 to 15 years with varying levels of ASD severity to receive either 10 mg/kg of suramin, 20 mg/kg of suramin or placebo at study baseline, week 4 and week 8. The trial was conducted in South Africa, where suramin is approved. Eight participants dropped out of the phase 2 trial before it could be completed, including five who withdrew because of COVID-19 and one who withdrew due to a serious adverse event — status epilepticus, which occurred in a child in the 20 mg/kg group who had several risk factors for seizure — that “resolved without sequelae,” the researchers wrote.
The findings, presented at the virtual American Academy of Child and Adolescent Psychiatry Annual Meeting, showed that children who received the 10 mg/kg dose experienced a “sustained benefit” throughout the trial.
Specifically, these children’s Aberrant Behavior Checklist scores — a previously validated measure of irritability, agitation, crying, lethargy, social withdrawal, stereotypic behavior, hyperactivity, noncompliance and inappropriate speech in children with a mental disability — improved from baseline by a mean of 12.5 points ± 3.18 points in the 10 mg/kg cohort and by a mean of 8.9 points ± 2.86 points in the placebo group by week 14, although the change was not significant. Meanwhile, the scores of children in the placebo cohort improved 8.9 points ± 2.86 points and the scores of children in the 20 mg/kg cohort “did not show improvement” at week 14, the researchers reported. The younger patients with less severe autism who received 10 mg/kg experienced greater differences in Aberrant Behavior scores compared with other 10 mg/kg recipients.
In addition, Clinician’s Global Impression of Improvement scores — which considered components such as patient’s history, psychosocial circumstances, symptoms, behavior and the impact of symptoms on ability to function — improved from baseline to week 14 by a mean of 2.8 points ± 0.3 point (P = .016) in the 10 mg/kg cohort, 2 points ± 0.28 point (P = .65) in the 20 mg/kg cohort and 1.7 points ± 0.27 point in the placebo cohort.
“Early work in mouse models of ASD had established that suramin was a new potential treatment and another investigator had tried suramin in 10 boys with ASD,” Hough said. “This study built on the earlier work and was designed to establish that suramin was safe and tolerable and showed positive findings. We learned a great deal in this study about the dosing, safety, tolerability and efficacy in this pediatric population.”
He added that the company met with the FDA prior to the society’s annual meeting to discuss the findings. After Paxmedica representatives file an investigational new drug application next year, the company intends to coordinate a larger study involving suramin, Hough said.
References:
Aman AG, et al. Am J Ment Defic. 1985;89(5):485-91.
Busner J, Targum SD, et al. Psychiatry (Edgemont). 2007;(7):28-37.
CDC. Data and statistics on autism spectrum disorder. https://www.cdc.gov/ncbddd/autism/data.html. Accessed Nov. 3, 2021.
Hough D. Suramin intravenous infusion for treating boys with autism spectrum disorder: Results of a 14-week, randomized, double blind, placebo controlled, multidose, phase 2 study. Presented at: American Academy of Child and Adolescent Psychiatry Annual Meeting; Oct. 18-30, 2021 (virtual meeting).
Naviaux RK, et al. Ann Clin Transl Neurol. 2017;doi:10.1002/acn3.424.
Paxmedica. Our development pipeline. https://www.paxmedica.com/pipeline. Accessed Nov. 2, 2021.
Perspective
Back to Top
David Beversdorf, MD
Although the jury is still out on PAX-101, the results presented by Hough are interesting.
The sample size in their study is quite small, as might be expected in a phase 2 study. The primary outcome measure, the Aberrant Behavior Checklist, did not yield a significant effect, aside from a subset analysis for the younger participants with milder symptoms, but a subset analysis of an already small sample size must be viewed with caution. However, the secondary outcome, the Clinician’s Global Impression of Improvement, did reveal a significant benefit. These are both rather standard assessments for trials, but it is of interest that the most global measure demonstrated a response.
The study was also interesting that in all of the benefits were seen at the low dose, not the high dose. This follows a 2017 study suggesting improvement on the Autism Diagnostic Observation Scale, but that study only had five participants in each group.
The message for health care professionals at this stage is to keep watching for the subsequent studies on PAX-101. The results here are from too early of a trial to guide any clinical recommendation, but that could, of course, change, with a larger, more definitive trial.
Reference:
Naviaux RK, et al. Ann Clin Transl Neurol. 2017;doi:10.1002/acn3.424.
MU Health Care and the University of Missouri
Collapse
Click Here to Manage Email Alerts