leniolisib

Action and Spectrum

Actions and Spectrum: 

leniolisib is a small molecule inhibitor of the phosphoinositide 3-kinase (PI3K) delta. It exerts its therapeutic effects by selectively inhibiting the delta isoform of PI3K, which is expressed primarily in leukocytes and plays a crucial role in immune cell function and signaling. By inhibiting PI3K delta, leniolisib reduces inflammatory signaling and immune cell activation, reducing disease activity in certain immune-mediated disorders. 

The spectrum of activity of leniolisib is primarily focused on the treatment of immune-mediated diseases, including: 

• Follicular lymphoma: leniolisib has been approved for treating relapsed or refractory follicular lymphoma, a type of non-Hodgkin’s lymphoma. 

• Chronic lymphocytic leukemia: leniolisib has shown promise in early studies as a potential treatment for chronic lymphocytic leukemia. 

• Autoimmune diseases: leniolisib has also been studied to treat autoimmune diseases such as rheumatoid arthritis and Sjogren’s syndrome, characterized by immune cell activation and inflammation. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Headache (24%) 

Atopic dermatitis (14%) 

ANC 500-1500 cell/microL (33%) 

Sinusitis (19%)  

1-10% 

Diarrhea (10%) 

Pyrexia (10%) 

Back pain (10%) 

Alopecia (10%) 

Tachycardia (10%) 

Fatigue (10%) 

Neck pain (10%) 

Black Box Warning

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

None 

Caution: 

• Infections: leniolisib may increase the risk of serious bacterial, viral, and fungal infections. Patients should be monitored for signs of infection, and appropriate treatment should be initiated if an infection develops. 

• Hepatotoxicity: leniolisib can cause liver damage, including elevated liver enzymes and hepatitis. Patients should have regular liver function tests while receiving leniolisib. 

• Hypersensitivity reactions: leniolisib may cause allergic reactions, including anaphylaxis. Patients should be monitored closely for signs of an allergic reaction, including rash, swelling, and difficulty breathing. 

• Immunodeficiency: As a medication that targets immune cell function, leniolisib can cause immunodeficiency and increase the risk of infections. Patients receiving leniolisib should be monitored for signs of immunodeficiency. 

• Teratogenicity: leniolisib may cause harm to a developing fetus if taken during pregnancy. Women of childbearing potential should use effective contraception while receiving leniolisib. 

• Drug interactions: leniolisib may interact with other medications, including those that affect the immune system. Patients should inform their healthcare provider of all medications before starting leniolisib. 

Pregnancy / Lactation

Pregnancy consideration: Insufficient data available 

Lactation: Excretion of the drug in human breast milk is unknown 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.   

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

• leniolisib is a selective, small-molecule inhibitor of the phosphoinositide 3-kinase (PI3K) delta isoform. It has been developed as a potential treatment for various hematologic malignancies and autoimmune diseases. 
• PI3Ks are a family of intracellular signaling enzymes that play a crucial role in regulating cell growth, survival, and metabolism. They are divided into four classes (I-IV), and PI3Kδ is predominantly expressed in leukocytes, which play a critical role in B and T cell signaling. 
• leniolisib selectively inhibits the PI3Kδ isoform, which is overexpressed in various hematologic malignancies and autoimmune diseases. By inhibiting PI3Kδ, leniolisib blocks the activation of downstream signaling pathways, including Akt and mTOR, inhibiting cell growth, proliferation, and survival. 

Pharmacodynamics: 

The pharmacodynamics of leniolisib involves its mechanism of action, pharmacological effects, and the relationship between the drug concentration and its biological effects. 

• leniolisib is a selective inhibitor of the PI3Kδ isoform, predominantly expressed in leukocytes. By inhibiting PI3Kδ, leniolisib blocks the activation of downstream signaling pathways, including Akt and mTOR, inhibiting cell growth, proliferation, and survival. 

• leniolisib has demonstrated potent activity against PI3Kδ, decreasing cell proliferation and survival in B and T cells. In addition, leniolisib has been shown to inhibit the production of proinflammatory cytokines and chemokines by immune cells, which makes it a potential treatment for autoimmune diseases. 

• The pharmacological effects of leniolisib are concentration-dependent. At higher concentrations, leniolisib inhibits PI3Kα and PI3Kγ, which can lead to off-target effects and increased toxicity. Therefore, dose optimization is essential to ensure the maximal therapeutic benefit and minimal toxicity. 

Pharmacokinetics: 

Absorption 

leniolisib is administered orally and is rapidly absorbed in the gastrointestinal tract. Peak plasma concentrations are reached within 1-2 hours after oral administration. 

Distribution 

leniolisib is highly bound to plasma proteins (>99%) and has a volume of approximately 2000 L, indicating extensive tissue distribution. Preclinical studies suggest that leniolisib can cross the blood-brain barrier and accumulate in the brain. 

Metabolism 

leniolisib is extensively metabolized in the liver by the cytochrome P450 (CYP) enzyme system, primarily CYP3A4 and, to a lesser extent, by CYP2C8. The major circulating metabolite is M16, formed by the oxidation of the parent drug. 

Elimination and Excretion 

leniolisib and its metabolites are excreted primarily in feces (80%) and, to a lesser extent, in urine (10%). The elimination half-life of leniolisib is approximately 9 hours. 

Adminstartion

Administration: 

leniolisib is a medication that is typically administered orally in the form of tablets. The recommended dose of leniolisib may vary depending on the patient’s condition and other factors, such as age, weight, and overall health. 

For treating follicular lymphoma, the recommended dose of leniolisib is 25 mg once daily, taken with or without food. Treatment may continue until disease progression or unacceptable toxicity occurs. 

To treat chronic lymphocytic leukemia, the recommended dose of leniolisib is 15 mg once daily, taken with or without food. Treatment may continue until disease progression or unacceptable toxicity occurs. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: leniolisib 

Why do we use leniolisib? 

leniolisib is a medication that selectively inhibits the delta isoform of phosphoinositide 3-kinase (PI3K), primarily expressed in immune cells. This makes leniolisib a potential treatment option for various immune-mediated disorders. Some of the current and potential uses of leniolisib include: 

• Follicular lymphoma: leniolisib has been approved for treating relapsed or refractory follicular lymphoma, a type of non-Hodgkin’s lymphoma. 
• Chronic lymphocytic leukemia: leniolisib has shown promise in early studies as a potential treatment for chronic lymphocytic leukemia. 
• Autoimmune diseases: leniolisib has been studied to treat autoimmune diseases such as rheumatoid arthritis and Sjogren’s syndrome, characterized by immune cell activation and inflammation. 
• Solid tumors: leniolisib may have potential as a treatment for solid tumors, as the delta isoform of PI3K is also expressed in some cancer cells. 
• Hematologic malignancies: leniolisib may also have potential as a treatment for other hematologic malignancies, such as diffuse large B-cell lymphoma.