In interim guidance posted last week, the American Academy of Paediatrics (AAP) said it does not recommend the routine use of leucovorin for children with autism, despite calls by the Trump administration to do so, reports Fierce Pharma.
In September, after US health officials positioned the decades-old drug as a treatment for cerebral folate deficiency (CFD) – present in some children with autism spectrum disorder (ASD) – it urged the association to provide guidance on the medication.
As the FDA works with GSK to allow the British pharma’s previously discontinued leucovorin product Wellcovorin to treat CFD, the Department of Health and Human Services had said that the move would “authorise treatment for children with ASD”, and that state Medicaid programmes will be able to cover the drug for the indication of autism.
But in its “interim guidance” on Friday, the AAP said: “The current evidence base remains too limited to support recommendations,” suggesting that large clinical trials are needed to determine leucovorin’s efficacy and safety profile for the broader autism population.
In its September release, the HHS had said the National Institutes of Health would launch confirmatory trials and new research into the effects of leucovorin.
In some children with autism, folate receptor alpha (FRα) autoantibodies block the transport of folate – a B vitamin – into the brain, leading to CFD.
Leucovorin, or folinic acid, bypasses the defective folate transport system and delivers folate directly to the brain, according to an HHS fact sheet.
To back its decision on Wellcovorin, the FDA cited a “systematic analysis of literature published between 2009-2024, including case reports … as well as mechanistic data”.
In a double-blind, placebo-controlled trial among 80 patients, researchers in India recorded better changes in Childhood Autism Rating Scale scores, as well as better changes in behavioural problems measured by the Child Behaviour Checklist, for those who took leucovorin versus placebo.
In the leucovorin group, improvement was more pronounced in children with higher levels of folate receptor autoantibodies.
The study was clearly too small, based on a recent Centres for Disease Control and Prevention estimate that in 2022, one in 31 children was diagnosed with autism by the age of eight in the US.
The APP acknowledged that small studies have pointed to “potential benefit in carefully selected cases”, and that these “preliminary results are promising and have laid the groundwork for further investigation”.
But the organisation also said guidance needs “to be grounded in both scientific rigour and respect for neurodiversity”.
The association previously blasted the government for linking autism to childhood vaccines and to the use of the pain reliever acetaminophen during pregnancy without evidence. It also criticised the administration for aggressively promoting leucovorin as an autism treatment.
AAP President Susan Kressly, MD, said in a statement that “dangerous claims and misleading information send a confusing message to parents and expecting parents and does a disservice to autistic individuals”.
“Don’t take Tylenol,” President Donald Trump said at a September press conference, referring to the original Kenvue drug by its brand name.
But during an October event, Health Secretary Robert R Kennedy Jr said there is not sufficient evidence to definitely link Tylenol to autism.
“The causative association… between Tylenol given in pregnancy and the perinatal periods is not sufficient to say it definitely causes autism. But it is very suggestive,” Kennedy said.
Kenvue has pushed back against the claim by the Trump administration, having urged the FDA not to change the label of the popular pain medication over the uncorroborated link between its pregnancy use and autism.
Meanwhile, Texas Attorney-General Ken Paxton has filed a new lawsuit against the Johnson & Johnson consumer health spinoff, alleging the company “deceptively” marketed Tylenol to pregnant women despite knowing exposure to the drug can cause a “significantly increased risk of autism and other disorders”.
See more from MedicalBrief archives:
Texas AG sues makers of Tylenol for ‘hiding autism risks’
SA expert groups dismiss Trump's paracetamol link to autism