FDA knocks back Pharming's bid for wider Joenja use

The FDA has turned down an attempt by Pharming to broaden the label of its Joenja drug for a rare immunodeficiency disorder so it can be used in younger patients.

The US regulator sent a complete response letter (CRL) to the Netherlands biopharma company, denying its application to expand the use of Joenja (leniolisib) to include patients aged four to 11 with activated phosphoinositide 3-kinase delta syndrome (APDS), an ultra- rare primary immunodeficiency.

In 2023, Joenja became the first FDA-approved treatment for people aged 12 and over living with APDS, which makes patients vulnerable to severe, recurrent sinopulmonary infections, autoimmune conditions, and inflammatory damage to the small intestine.

Roughly a third of APDS patients don't live beyond 50, with blood cancers the most common cause of death. It is caused by mutations in either the PIK3CD or PIK3R1 genes, leading to hyperactivity of PIK3 delta, which can be inhibited using Joenja.

According to Pharming, the FDA has raised an issue with the potential for underexposure in lower-weight paediatric APDS patients, asking for additional pharmacokinetic studies to "reassess the proposed paediatric doses and confirm that children in the lower weight dose groups can achieve exposure levels comparable to the approved adult and adolescent regimen."

It added that the CRL has also identified an issue with one of the analytical methods used for production batch testing.

"We believe we can address the clinical pharmacology and batch testing methodology issues outlined in the letter, and we plan to work closely with the FDA to meet the agency's requirements and determine next steps for resubmission," said Pharming in a statement.

Joenja is a sizeable contributor to Pharming's revenues, accounting for €38 million ($45 million) of its total sales of €70 million in the first nine months of 2025, with the remainder made up of revenues from hereditary angioedema therapy Ruconest (conestat alfa), which is starting to approach the end of its patent life in the US.

Joenja is key to Pharming's growth in the coming years, and the company has previously said that will be driven by expansion into the four to 11 age bracket as well as launches in additional markets.

Chief executive Fabrice Chouraqui said he is "disappointed in the FDA's response," given Joenja's ability to "address the immune dysregulation and deficiency that drive APDS, and significantly impact the long-term course of disease in this population." As it stands, there is still no FDA-approved therapy for the younger APDS population.

"We are going to work closely with the FDA to provide the necessary information and determine the best and most effective path forward," he added.

Joenja is also under review in Europe, Japan, Canada, and several other countries for APDS, and was also approved for the 12-plus age group in the UK in 2024. Pharming is also developing the drug for other primary immunodeficiency indications.