Joenja - Pharming Healthcare Inc.

Verify pregnancy status in females of reproductive potential prior to initiating treatment with JOENJA [see Warnings and Precautions (5.1), and Use in Specific Populations (8.1, 8.3)].

The recommended dosage is based on weight as provided in Table 1.

Administer JOENJA orally twice daily approximately 12 hours apart, with or without food.

Missed Dose(s)

• Advise patients that if a dose is missed by more than 6 hours, wait and take the next dose at the usual time.
• Advise patients that if vomiting occurs within 1 hour after taking JOENJA, take JOENJA as soon as possible. If vomiting occurs more than 1 hour after dosing, wait and take the next dose at the usual time.

Based on findings in animals, JOENJA may cause fetal harm when administered to a pregnant woman. Administration of leniolisib to rats and rabbits during the period of organogenesis caused embryo-fetal toxicity including malformations at exposures that were 2-6 times higher than the maximum recommended human dose (MRHD) in APDS patients based on AUC comparisons. Verify the pregnancy status of patients of reproductive potential prior to starting treatment. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use highly effective contraception during treatment and for 1 week after the last dose [see Dosage and Administration (2.1), Use in Specific Populations (8.1, 8.3)].

Live, attenuated vaccinations may be less effective if administered during JOENJA treatment.

Hypersensitivity reaction(s), including anaphylaxis, have been reported in the postmarketing setting. If a clinically significant hypersensitivity reaction occurs, discontinue JOENJA and institute appropriate therapy [see Adverse Reactions (6.2)].

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adverse Reactions in Patients 12 Years of Age and Older with APDS

The safety of JOENJA reflects exposure based on 38 adult and pediatric patients 12 years of age and older with activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS) from the placebo-controlled portion of Study 2201 [see Clinical Studies (14)] and additional open-label clinical safety data. Thirty-seven of 38 patients received JOENJA 70 mg orally twice daily for at least 25 weeks and 66% were exposed for 96 weeks or longer. Median duration of JOENJA treatment was approximately 2 years, and 4 patients had more than 5 years of JOENJA exposure.

The data below are based on the 12-week, placebo-controlled portion of Study 2201 in which either JOENJA 70 mg (N=21) or placebo (N=10) was administered twice daily to patients with APDS. Demographics of the patients who participated in this study are summarized in Clinical Studies [see Clinical Studies (14)]. Table 2 presents the number of patients and incidence, rounded to the nearest percent, of adverse reactions that occurred in 2 or more patients treated with JOENJA and for which the incidence in patients treated with JOENJA was greater than the incidence in patients treated with placebo.

The most common adverse reactions (> 10%) were headache, sinusitis, and atopic dermatitis.

The following adverse reactions have been identified during postapproval use of JOENJA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Immune System Disorders: hypersensitivity (anaphylaxis)

Based on findings from animal studies, JOENJA may cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)].

The safety and effectiveness of JOENJA for the treatment of activated phosphoinositide 3-kinase delta syndrome have been established in pediatric patients 4 years of age and older who weigh 27 kg or greater. Use of JOENJA for this indication is supported by evidence from an adequate and well-controlled study in adult and pediatric patients 12 years of age and older (Study 2201) [see Clinical Studies (14)], and safety and pharmacokinetic data from a single-arm, open-label study (Study LE 3301) in pediatric patients 4 years to less than 12 years of age. A total of 8 pediatric patients aged 4 to less than 12 years in Study LE3301 received the recommended dosage of JOENJA based on body weight. The pharmacokinetic data demonstrated no clinically significant difference between pediatric patients younger than 12 years of age and adult and pediatric patients 12 years of age and older [see Clinical Pharmacology (12.3)]. Safety of JOENJA in pediatric patients aged 4 years to less than 12 years were consistent with adult and pediatric patients aged 12 years and older. Additional adverse reactions reported in pediatric patients aged 4 years to less than 12 years who weigh 27 kg or greater were abdominal pain, cough, and respiratory tract infection [see Adverse Reactions (6.1)].

The safety and effectiveness of JOENJA have not been established in pediatric patients younger than 4 years of age or who weigh less than 27 kg.

Because clinical studies of JOENJA did not include any patients 65 years of age and older, it cannot be determined whether they respond differently from younger adult patients.

Leniolisib is extensively (60%) metabolized by the liver. The effect of hepatic impairment on the pharmacokinetics of leniolisib has not been studied. The use of JOENJA in patients with moderate to severe hepatic impairment is not recommended [see Clinical Pharmacology (12.3)].

Leniolisib inhibits PI3K-delta by blocking the active binding site of PI3K-delta. In cell-free isolated enzyme assays, leniolisib was selective for PI3K-delta over PI3K-alpha (28-fold), PI3K-beta (43-fold), and PI3K-gamma (257-fold), as well as the broader kinome. In cell-based assays, leniolisib reduced pAkt pathway activity and inhibited proliferation and activation of B and T cell subsets. Gain-of-function variants in the gene encoding the p110-delta catalytic subunit or loss of function variants in the gene encoding the p85-alpha regulatory subunit each cause hyperactivity of PI3K-delta. Leniolisib inhibits the signaling pathways that lead to increased production of PIP3, hyperactivity of the downstream mTOR/Akt pathway, and to the dysregulation of B and T cells.

Ex vivo pharmacodynamics of leniolisib [proportion of phosphorylated Akt (pAkt)-positive B cells] were assessed intra-individually at 10, 30, and 70 mg twice daily for 4 weeks at each dose level in adult patients with APDS (N=6). Within the explored dose range, higher leniolisib plasma concentrations were generally associated with higher reduction of pAkt-positive B cells and higher doses were associated with a slightly higher peak reduction as well as more sustained reduction. Treatment with JOENJA 70 mg twice a day at steady state is estimated to produce time-averaged reduction of pAkt-positive B cells by approximately 80%.

The systemic drug exposure (AUC and C_max) of leniolisib increased dose proportionally within the studied range of doses (20 to 140 mg twice a day dosing and single doses of 10 to 400 mg) in healthy adult participants. During twice daily dosing approximately 12 hours apart, leniolisib accumulates approximately 1.4-fold (range of 1.0 to 2.2) in achieving steady-state, consistent with an effective half-life (t_1/2) of approximately 7 hours. Steady state drug concentrations can be expected to be reached after approximately 2 to 3 days of JOENJA treatment. The pharmacokinetics of leniolisib are similar between healthy participants and APDS patients.

Leniolisib was not carcinogenic in the 6-month carcinogenicity study in Tg.rasH2 transgenic mice at doses up to 80 mg/kg/day.

Leniolisib was not genotoxic in the in vitro Ames assay, in vitro chromosomal aberration assay in human lymphocytes, or micronucleus assays in TK6 cells (in vitro) and rats (in vivo).

In a fertility study, male rats had decreased round spermatids and decreased spermatocytes in the testis at an oral dose of 90 mg/kg/day (approximately 2 times the MRHD on an AUC basis). Leniolisib had no effect on fertility in female rats at oral doses up to 90 mg/kg/day (approximately 4 times the MRHD on an AUC basis). No effects on male or female fertility and reproductive performance indices were observed up to the maximum dose administered of 90 mg/kg/day (approximately 2-4 times the MRHD on an AUC basis).

Storage and Handling

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Do not refrigerate.

Embryo-Fetal Toxicity

• Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1, 8.3)].
• Advise females of reproductive potential to use highly effective contraception during treatment with JOENJA and for 1 week after the last dose [see Warnings and Precautions (5.1) and Use in Specific Populations (8.3)].

Vaccinations

Instruct patients to inform the healthcare providers that they are taking JOENJA prior to a potential vaccination [see Warnings and Precautions (5.2)].

Risk of Hypersensitivity Reactions, Including Anaphylaxis

Advise patients to discontinue JOENJA and to seek immediate medical attention if they develop any signs and symptoms of serious allergic reactions [see Warnings and Precautions (5.3)].

Lactation

Advise women not to breastfeed during treatment with JOENJA and for 1 week after the last dose [see Use in Specific Populations (8.2)].

Administration

Advise patients JOENJA may be taken with or without food [see Dosage and Administration (2.2)].

Instruct patients that if they miss a dose by more than 6 hours, skip the missed dose. Advise patients to take the next dose as scheduled [see Dosage and Administration (2.2)].

Instruct patients that if vomiting occurs within 1 hour after taking JOENJA, take a dose as soon as possible [see Dosage and Administration (2.2)].

Manufactured for:
Pharming Healthcare Inc.,
10 Independence Blvd.
Warren, NJ USA 07059

JOENJA is a trademark of Pharming Intellectual Property B.V.

©2026 Pharming Technologies B.V. All rights reserved.

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