What Is Joenja?
Joenja (Leniolisib) belongs to the group of kinase inhibitors used to treat activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS). It is prescribed for adults and pediatric patients (from 12 years of age). Joenja film-coated tablets are intended for oral use and contain 70 mg of Leniolisib. [citation].
Figure 1: Chemical Structure Depiction of Leniolisib, Source
Shortly About Activated phosphoinositide 3-kinase delta syndrome
Activated phosphoinositide 3-kinase delta syndrome (APDS), also known as PI3Kδ syndrome, is a rare primary immunodeficiency disease that results in a mutation of the PIK3CD or PIK3R1 genes, more specifically, the gene encoding the p110δ catalytic subunit of the phosphoinositide 3-kinase delta (PI3Kδ) enzyme. PI3Kδ is an enzyme involved in a signaling pathway that is crucial in regulating various cellular processes, including immune cell development and function. In APDS, the mutations in the gene result in the constitutive activation of the PI3Kδ enzyme, leading to excessive signaling through this pathway which further affects humoral and cellular immunity [citation].
The excessive activation of PI3Kδ disrupts the normal functioning of immune cells, particularly T and B cells, which are essential for the body's defense against infections. As a result, individuals with PI3Kδ syndrome often experience recurrent respiratory tract infections, such as sinusitis, bronchitis, and pneumonia. They may also be prone to certain viral and fungal infections [citation].
In addition to recurrent infections, PI3Kδ syndrome can also manifest with other clinical features, including enlarged lymph nodes and spleen, autoimmunity (such as autoimmune cytopenias and inflammatory bowel disease), and an increased risk of developing certain types of cancer, particularly lymphomas [citation].
The diagnosis of PI3Kδ syndrome is typically confirmed through genetic testing to identify the specific mutations in the PIK3CD gene, which encodes the p110δ subunit. Treatment options for PI3Kδ syndrome are limited, and management usually involves a multidisciplinary approach focused on addressing the specific symptoms and complications experienced by the individual. This may include using antibiotics for infections, immunosuppressive medications for autoimmune manifestations, and close monitoring for the development of malignancies. Genetic counseling is also recommended for affected individuals and their families [citation; citation].
For What Is Used Joenja?
The FDA approved Joenja (Leniolisib) on March 24, 2023, making it the first treatment for APDS [citation]. APDS was first described in 2013; since then, about 200 patients have been recorded with symptoms that indicate it. However, this disease can go undiagnosed due to incorrect observation of symptoms, so patients are treated as patients with unclassified immunodeficiency.
Symptoms usually include the following:
Recurrent bacterial and viral respiratory tract infections,
Gastrointestinal disease,
Non-malignant lymphoproliferation,
Autoimmune thyroiditis,
and susceptibility to EBV [citation].
Who Developed Joenja?
Global biopharmaceutical company Pharming Healthcare Inc. labels Joenja, which was previously developed by Novartis [citation; citation].
What Is the Mechanism of Action?
Leniolisib blocks the active binding site of PI3K-delta and thus serves as an inhibitor of the PI3K-delta pathway, blocking the active binding site in the p110δ subunit. Compared to other PI3K types (PI3K-alpha, PI3K-beta, and PI3K-gamma), during the test, it was found that this inhibitor is selective for PI3K-delta. The result is decreased proliferation of B and T cell subsets [citation; citation].
This drug mediates the PI3K/AKT pathway, which affects cell proliferation, growth, and survival. In addition to the fact that certain members of the PI3K family are involved in inflammation and autoimmunity, the PI3K signaling pathway is usually dysregulated or incorrectly activated in cancer cells [citation].
Treatment of hematological malignancies with the help of such inhibitors is vital because the PI3K/AKT hyperactive pathway is characteristic of this phenomenon [citation].
What Are the Key Advantages of Joenja?
The key advantages of Leniolisib are:
In addition, before the final approval of Joenja, the patients were given antibiotics or different groups of drugs for the immune system to cope with APDS symptoms [citations;citation].
What Are the Key Warnings and Precautions?
Warnings for Leniolisib have been issued for:
Embryo-fetal toxicity. Other examples of toxicity were not reported.
Possibility of less vaccine effectiveness [citation].
What Are the Key Adverse Reactions?
Adverse reactions to this drug are recorded in more than 10% of cases and include:
Headache
Sinusitis
Atopic dermatitis [citation].
Less frequent side effects include: Tachycardia, Diarrhea, Fatigue, Pyrexia, neck, and back pain, and Alopecia [citation].