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  1. News & Events for Human Drugs

FDA approves first treatment for activated phosphoinositide 3-kinase delta syndrome


FDA has approved Joenja (leniolisib) tablets as the first treatment for activated phosphoinositide 3-kinase delta syndrome in adult and pediatric patients 12 years of age and older. Patients weighing at least 45 kg take 70 mg orally twice a day, approximately 12 hours apart.

Disease or Condition

Activated PI3K-delta syndrome (APDS) is a genetic disorder that impairs the immune system. Individuals with this condition often have low numbers of white blood cells, particularly certain types of B cells and T cells. These cells are necessary to recognize and attack foreign invaders, such as viruses and bacteria, to prevent infection. People with APDS develop recurrent infections, particularly in the sinuses, ears, and respiratory tract. They also develop enlarged lymph nodes, tonsils, and other organs that can cause obstruction in the airway and gastrointestinal tract. Patients with APDS are more prone to develop blood cell cancers, like lymphoma.

APDS is caused by mutations in the PIK3CD or PIK3R1 genes that encode a protein called phosphoinositide-3 kinase d (PI3Kd), which is important for the normal development and function of white blood cells in the body.


The efficacy of Joenja was evaluated in the placebo-controlled portion of Study 2201 (NCT02435173), a 12‑week blinded, randomized, placebo-controlled study of 31 adult and pediatric patients 12 years of age and older with confirmed APDS-associated genetic PI3Kδ mutation, with a documented variant in either PIK3CD or PIK3R1.

During the study, 21 patients received 70 mg of Joenja and 10 received placebo twice a day for 12 weeks. The co‑primary efficacy endpoints were improvement in lymphoproliferation (or reduction in the size of lymph nodes) and the normalization of immunophenotype as measured by the percentage of naïve B cells out of total B cells.

By day 85 of the study, patients taking Joenja saw a reduction in lymph node size and a 37 percent improvement in naïve B cells counts compared to placebo, indicating a correction of the underlying immune defect.

Safety Information

The most common side effects of Joenja were headache, sinusitis, and atopic dermatitis. Joenja may cause fetal harm; patients should be advised of the potential risk to a fetus and patients’ pregnancy status should be verified prior to starting treatment. Patients with moderate to severe hepatic impairment should not use Joenja. See full prescribing information for additional information on risks associated with Joenja.


Joenja received orphan drug designation, rare pediatric disease designation, and priority review.

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