Pharming Group receives Complete Response Letter from U.S. FDA for sNDA for Joenja® (leniolisib) in children aged 4 to 11 years with APDS

Rhea-AI Summary

Pharming Group (Euronext: PHARM; Nasdaq: PHAR) received a U.S. FDA Complete Response Letter (CRL) for the sNDA seeking approval of Joenja (leniolisib) for children aged 4–11 with APDS due to potential underexposure in lower-weight pediatric patients and an analytical batch-testing method issue.

Pharming plans a Type A meeting with the FDA and says the approved indication for patients 12 and older remains unaffected; the sNDA was based on positive Phase III data showing lymphadenopathy reduction and naive B cell increases.

Positive

• U.S. approval for Joenja in patients ≥12 years remains unaffected
• Phase III data showed improved lymphadenopathy and increased naïve B cells
• Company plans to request a Type A meeting to address FDA questions

Negative

• FDA cited potential underexposure in lower-weight 4–11 year olds requiring more pediatric PK data
• FDA identified an issue with one analytical method used for production batch testing
• CRL will likely delay pediatric availability for ages 4–11

Key Figures

Pediatric age range: 4 to 11 years Existing approval age: 12 years and older Treatment duration: 12 weeks +5 more

8 metrics

Pediatric age range 4 to 11 years Children with APDS in sNDA

Existing approval age 12 years and older Joenja FDA-approved APDS population

Treatment duration 12 weeks Phase III study improvements period

Safety follow-up 8 months Safety data included in sNDA

Dose levels 4 dose levels Pediatric Phase III study dosing

Priority Review date October 2025 FDA Priority Review grant for sNDA

Initial FDA approval March 2023 Joenja approval in ≥12-year-old APDS patients

Publication date February 1, 2026 Date of CRL announcement

Market Reality Check

normal vol

Market Pulse Summary

This announcement highlighted a regulatory setback for expanding Joenja to children aged 4–11 with A...

Analysis

This announcement highlighted a regulatory setback for expanding Joenja to children aged 4–11 with APDS, as the FDA issued a Complete Response Letter requesting additional pharmacokinetic data and clarification on batch testing methods. Joenja’s approval in patients aged 12 and older, granted in March 2023, remained unchanged. The sNDA was supported by a Phase III study showing improvements over 12 weeks and 8 months of safety data, but timelines now depend on future interactions with the FDA.

Key Terms

complete response letter, supplemental new drug application, pharmacokinetic, type a meeting, +1 more

5 terms

complete response letter regulatory

"FDA has issued a Complete Response Letter (CRL) to its supplemental"

A complete response letter is an official communication from a drug or medical-device regulator, such as the U.S. Food and Drug Administration (FDA), telling a company that a marketing application cannot be approved in its current form and listing the specific deficiencies to be fixed. For investors it matters because it pauses or delays a product’s path to market—like a building inspector issuing a list of repairs before a certificate of occupancy—affecting revenue timing, costs and stock value.

supplemental new drug application regulatory

"Complete Response Letter (CRL) to its supplemental New Drug Application (sNDA)"

A supplemental new drug application is a request submitted to regulatory authorities to make changes to an existing approved medication, such as adding new uses, strengths, or formulations. For investors, it signals that a pharmaceutical company is seeking approval for new product developments or expanded applications, which can impact the company's future sales, market potential, and stock value.

pharmacokinetic medical

"requested additional pediatric pharmacokinetic data to reassess the proposed"

Pharmacokinetic describes how a drug moves through and leaves the body — how it is absorbed, spread to tissues, broken down and excreted — like tracking a package from pickup to delivery and disposal. For investors, these properties determine effective dose, safety risks, how often a medicine must be taken, and how reliably it works, which in turn influence clinical trial success, regulatory approval chances, production complexity and a drug’s commercial value.

type a meeting regulatory

"We plan to request a Type A meeting with the FDA."

A Type A meeting is an urgent, short-notice session requested between a company and a regulatory agency (for example, the FDA in the U.S.) to resolve critical issues that block a development program, such as a clinical hold or safety concern. Investors care because the outcome can immediately affect whether a clinical trial or approval process resumes, changing timelines, costs and the company’s near-term value — like calling an emergency mechanic when a car won’t start so a trip can continue.

priority review regulatory

"In October 2025, the FDA granted the application Priority Review1 based on"

Priority review is a regulatory fast-track that shortens the time an agency spends evaluating a drug, vaccine or medical device application so a decision comes sooner than normal. For investors, it matters because a faster review is like an express lane to market: it can speed revenue potential and reduce regulatory uncertainty, but it does not guarantee approval and still requires the product to meet safety and effectiveness standards.

AI-generated analysis. Not financial advice.

Leiden, the Netherlands, February 1, 2026: Pharming Group (Euronext: PHARM; Nasdaq: PHAR) today announced that the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL) to its supplemental New Drug Application (sNDA) for Joenja® (leniolisib), an oral, selective phosphoinositide 3-kinase delta (PI3Kδ) inhibitor, as a treatment for children aged 4 to 11 years with activated phosphoinositide 3-kinase delta syndrome (APDS), a rare primary immunodeficiency.

The FDA raised an issue with the potential for underexposure in lower weight pediatric patients. As a result, the FDA has requested additional pediatric pharmacokinetic data to reassess the proposed pediatric doses and confirm that children in the lower weight dose groups can achieve exposure levels comparable to the approved adult and adolescent regimen. The letter also identified an issue with one of the analytical methods used for production batch testing, and the FDA requested additional data and clarification on this point.

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. We plan to request a Type A meeting with the FDA.

Joenja’s U.S. FDA approval for the treatment of APDS in patients aged 12 years of age and older is unaffected by this regulatory action.

Fabrice Chouraqui, Chief Executive Officer of Pharming, commented:

“While we are disappointed in the FDA’s response, we remain dedicated to making Joenja available to pediatric patients aged 4-11 with APDS. Joenja has the potential to address the immune dysregulation and deficiency that drive APDS and significantly impact the long-term course of disease in this population, for whom there is currently no approved targeted treatment. We are going to work closely with the FDA to provide the necessary information and determine the best and most effective path forward.”

Pharming submitted the sNDA to the FDA based on positive data from the open-label, multinational, single-arm Phase III study in children aged 4 to 11 years, which showed improvements over 12 weeks in two clinically relevant hallmarks of APDS, reduced lymphadenopathy and increased naïve B cells, together indicating a correction of the underlying immune defect. The submission also included safety data from 8 months of treatment. The improvements in lymphoproliferation and immunophenotype correction were seen across the four dose levels investigated and were consistent with the improvements previously reported in adolescent and adult patients. All treatment emergent adverse events were reported to be mild to moderate in nature. There were no drug related serious adverse events, and all patients completed the 12-week treatment period.

In October 2025, the FDA granted the application Priority Review¹ based on its guidelines stating the medicine would offer significant improvements in effectiveness or safety of the treatment, prevention, or diagnosis of serious conditions. Currently, there are no approved treatments for children with APDS under the age of 12 years globally. Joenja received approval from the FDA for the treatment of APDS in adult and pediatric patients 12 years of age and older in March 2023.

About Activated Phosphoinositide 3-Kinase δ Syndrome (APDS) 
APDS is a rare primary immunodeficiency that was first characterized in 2013. APDS is caused by variants in either one of two identified genes known as PIK3CD or PIK3R1, which are vital to the development and function of immune cells in the body. Variants of these genes lead to hyperactivity of the PI3Kδ (phosphoinositide 3-kinase delta) pathway, which causes immune cells to fail to mature and function properly, leading to immunodeficiency and dysregulation^2,3,4 APDS is characterized by a variety of symptoms, including severe, recurrent sinopulmonary infections, lymphoproliferation, autoimmunity, and enteropathy.^5,6 Because these symptoms can be associated with a variety of conditions, including other primary immunodeficiencies, it has been reported that people with APDS are frequently misdiagnosed and suffer a median 7-year diagnostic delay.⁷ As APDS is a progressive disease, this delay may lead to an accumulation of damage over time, including permanent lung damage and lymphoma.^5-8 A definitive diagnosis can be made through genetic testing. APDS affects approximately 1 to 2 people per million worldwide.

About leniolisib
Leniolisib is an oral small molecule phosphoinositide 3-kinase delta (PI3Kẟ) inhibitor approved in the U.S., U.K., Australia and Israel as the first and only targeted treatment of activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS) in adult and pediatric patients 12 years of age and older. Leniolisib inhibits the production of phosphatidylinositol-3-4-5-trisphosphate, which serves as an important cellular messenger and regulates a multitude of cell functions such as proliferation, differentiation, cytokine production, cell survival, angiogenesis, and metabolism. Results from a randomized, placebo-controlled Phase III clinical trial demonstrated statistically significant improvement in the coprimary endpoints, reflecting a favorable impact on the immune dysregulation and deficiency seen in these patients, and interim open label extension data has supported the safety and tolerability of long-term leniolisib administration.^9,10 Leniolisib is currently under regulatory review in the European Economic Area, Japan, Canada and several other countries for APDS. Leniolisib is also being evaluated in two Phase III clinical trials in children with APDS and in two Phase II clinical trials in primary immunodeficiencies (PIDs) with immune dysregulation. The safety and efficacy of leniolisib has not been established for PIDs with immune dysregulation beyond APDS.

About Pharming Group N.V.
Pharming Group N.V. (EURONEXT Amsterdam: PHARM/Nasdaq: PHAR) is a global biopharmaceutical company dedicated to transforming the lives of patients with rare, debilitating, and life-threatening diseases. We are developing and commercializing a portfolio of innovative medicines, including small molecules and biologics. Pharming is headquartered in Leiden, the Netherlands, with a significant proportion of its employees based in the U.S.

For more information, visit www.pharming.com and find us on LinkedIn.
  
Forward-looking Statements
This press release may contain forward-looking statements. Forward-looking statements are statements of future expectations that are based on management’s current expectations and assumptions and involve known and unknown risks and uncertainties that could cause actual results, performance, or events to differ materially from those expressed or implied in these statements. These forward-looking statements are identified by their use of terms and phrases such as “aim”, “ambition”, ‘‘anticipate’’, ‘‘believe’’, ‘‘could’’, ‘‘estimate’’, ‘‘expect’’, ‘‘goals’’, ‘‘intend’’, ‘‘may’’, “milestones”, ‘‘objectives’’, ‘‘outlook’’, ‘‘plan’’, ‘‘probably’’, ‘‘project’’, ‘‘risks’’, “schedule”, ‘‘seek’’, ‘‘should’’, ‘‘target’’, ‘‘will’’ and similar terms and phrases. Examples of forward-looking statements may include statements with respect to timing and progress of Pharming's preclinical studies and clinical trials of its product candidates, Pharming's clinical and commercial prospects, and Pharming's expectations regarding its projected working capital requirements and cash resources, which statements are subject to a number of risks, uncertainties and assumptions, including, but not limited to the scope, progress and expansion of Pharming's clinical trials and ramifications for the cost thereof; and clinical, scientific, regulatory, commercial, competitive and technical developments. In light of these risks and uncertainties, and other risks and uncertainties that are described in Pharming's 2024 Annual Report and the Annual Report on Form 20-F for the year ended December 31, 2024, filed with the U.S. Securities and Exchange Commission, the events and circumstances discussed in such forward-looking statements may not occur, and Pharming's actual results could differ materially and adversely from those anticipated or implied thereby. All forward-looking statements contained in this press release are expressly qualified in their entirety by the cautionary statements contained or referred to in this section. Readers should not place undue reliance on forward-looking statements. Any forward-looking statements speak only as of the date of this press release and are based on information available to Pharming as of the date of this release. Pharming does not undertake any obligation to publicly update or revise any forward-looking statement as a result of new information, future events or other information.

Inside Information
This press release relates to the disclosure of information that qualifies, or may have qualified, as inside information within the meaning of Article 7(1) of the EU Market Abuse Regulation.

References 

1. FDA. Priority Review. Available at: https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/priority-review Accessed October 2025.
2. Lucas CL, et al. Nat Immunol. 2014;15(1):88-97.
3. Elkaim E, et al. J Allergy Clin Immunol. 2016;138(1):210-218.
4. Nunes-Santos C, Uzel G, Rosenzweig SD. J Allergy Clin Immunol. 2019;143(5):1676-1687.
5. Coulter TI, et al. J Allergy Clin Immunol. 2017;139(2):597-606.
6. Maccari ME, et al. Front Immunol. 2018;9:543.
7. Jamee M, et al. Clin Rev Allergy Immunol. 2020 Dec;59(3):323-333.
8. Condliffe AM, Chandra A. Front Immunol. 2018;9:338.
9. Rao VK, et al Blood. 2023 Mar 2;141(9):971-983.
10. Rao VK, et al.  J Allergy Clin Immunol 2024;153:265-74.

 For further public information, contact:

Investor Relations
Michael Levitan, VP Investor Relations & Corporate Communications
T: +1 (908) 705 1696
E: investor@pharming.com

Media Relations
Global: Saskia Mehring, Corporate Communications Manager
T: +31 6 28 32 60 41
E: media.relations@pharming.com

U.S.: Ethan Metelenis (Precision AQ on behalf of Pharming)
T: +1 (917) 882-9038

Netherlands: Leon Melens (LifeSpring Life Sciences Communication on behalf of Pharming)
T: +31 6 53 81 64 27

Attachment

• FINAL_Pharming receives FDA CRL for Joenja sNDA in children_EN_1Feb26

FAQ

What did Pharming announce about the FDA decision on Joenja for children aged 4–11 (PHAR) on February 1, 2026?

The FDA issued a Complete Response Letter requiring more data on pediatric dosing and batch testing methods. According to Pharming, the CRL cites potential underexposure in lower-weight children and requests additional pediatric pharmacokinetic and analytical method data before resubmission.

Will the FDA CRL for the Joenja sNDA affect the existing approval for ages 12 and older (PHAR)?

No — the company says the existing U.S. approval for patients aged 12 and older is unaffected by the CRL. According to Pharming, the regulatory action applies only to the supplemental pediatric application for ages 4–11.

What specific data did the FDA request from Pharming for Joenja in younger children (PHAR)?

The FDA requested additional pediatric pharmacokinetic data to reassess proposed doses and confirm exposure in lower-weight groups. According to Pharming, the agency also asked for clarification and additional data on an analytical method used in production batch testing.

What are the next steps Pharming plans to take after receiving the FDA Complete Response Letter (PHAR)?

Pharming plans to request a Type A meeting with the FDA to agree on data needs and a resubmission path. According to Pharming, the company intends to work closely with the agency to provide the requested pharmacokinetic and analytical-method information.

How strong were the Phase III results supporting the Joenja sNDA for children 4–11 (PHAR)?

Phase III showed improvements in lymphadenopathy and increases in naïve B cells over 12 weeks, with reported mild-to-moderate adverse events. According to Pharming, results were consistent across four dose levels and aligned with adolescent and adult findings.