JOENJA Dosage & Rx Info | Uses, Side Effects

Joenja Generic Name & Formulations

Legal Class

General Description

Leniolisib 70mg; tabs.

Pharmacological Class

Kinase inhibitor.

How Supplied

Tabs—60

Storage

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. Store and dispense in original container.

Manufacturer

Pharming Healthcare Inc.

Generic Availability

Mechanism of Action

Leniolisib inhibits PI3K-delta by blocking the active binding site of PI3K-delta. 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 signalling pathways that lead to increased production of PIP3, hyperactivity of the downstream mTOR/AKT pathway, and to the dysregulation of B and T cells.

Joenja Indications

Indications

Treatment of activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS).

Joenja Dosage and Administration

Adults and Children

<12yrs: not established. ≥12yrs: (<45kg): not recommended; (≥45kg): 70mg twice daily (~12hrs apart).

Joenja Contraindications

Not Applicable

Joenja Boxed Warnings

Not Applicable

Joenja Warnings/Precautions

Warnings/Precautions

Moderate to severe hepatic impairment: not recommended. Embryo-fetal toxicity. Advise females of reproductive potential to use highly effective contraception during and for 1 week after the last dose. Pregnancy: exclude status prior to initiation. Nursing mothers: not recommended (during and for 1 week after the last dose).

Joenja Pharmacokinetics

Distribution

Plasma protein bound: 94.5%.

Metabolism

Hepatic (CYP3A4).

Elimination

Fecal (67%), renal (25.5%). Half-life: ~10 hours.

Joenja Interactions

Interactions

May reduce efficacy of live, attenuated vaccines. Potentiated by strong CYP3A4 inhibitors (eg, itraconazole); avoid concomitant use. Antagonized by moderate and strong CYP3A4 inducers; avoid concomitant use. Avoid concomitant drugs metabolized by CYP1A2 (with a narrow therapeutic index), and substrates of BCRP, OATP1B1, OATP1B3.

Joenja Adverse Reactions

Adverse Reactions

Headache, sinusitis, atopic dermatitis.

Joenja Clinical Trials

Clinical Trials

The approval was based on data from a phase 2/3 trial (ClinicalTrials.gov Identifier: NCT02435173) which evaluated the efficacy and safety of leniolisib in patients 12 years of age and older with APDS. Patients were randomly assigned 2:1 to receive either Joenja 70mg (n=21) or placebo (n=10) twice a day for 12 weeks. The coprimary efficacy endpoints were improvement in lymphoproliferation as measured by a change from baseline in lymphadenopathy measured by the log10-transformed sum of product diameters and the normalization of immunophenotype as measured by the percentage of naïve B cells out of total B cells.

Findings showed that leniolisib achieved a statistically significant reduction in index lymph node size (placebo-adjusted difference, -0.25; 95% CI, -0.38, -0.12; P =.0006) and for the percent improvement in naïve B cell counts (placebo-adjusted difference, 37.30; 95% CI, 24.06-50.54; P =.0002), compared with placebo.

Joenja

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