ICYMI: Enrollment Complete for Leniolisib Trial for APDS

According to a news release from late June 2021, biopharmaceutical company Pharming Group N.V. (“Pharming”) completed enrollment for a Phase 2/3 clinical trial evaluating leniolisib for patients with activated phosphoinositide 3-kinase delta (PI3K-delta) syndrome (APDS). As the current standard-of-care is more supportive than anything else, determining an effective treatment option could be huge for this patient population.


So what exactly is leniolisib? Initially developed by Novartis and licensed to Pharming in 2019, the treatment is an orally-administered PI3K-delta inhibitor. Through inhibiting PI3K-delta, the therapy also stops PIP3 from being produced. Normally, PIP3 plays a role in cell growth, proliferation, and metabolism. However, since patients with APDS causes B-cell and T-cell changes, inhibiting PI3K-delta and PIP3 could help control these naive B and T cells. In prior studies, leniolisib has been shown to be both safe and well-tolerated.

Within this particular Phase 2/3 clinical trial, researchers are exploring the efficacy of leniolisib. This will build upon past data from an open-label dose-escalation study, in which researchers evaluated the drug’s tolerability, safety, and both pharmacodynamic and pharmacokinetic profiles. In the efficacy portion of the study, 30 patients with APDS will enroll. Altogether, researchers seek to understand how leniolisib impacts lesion size and naive B cell percentage.

Activated PI3K-Delta Syndrome (APDS)

Overall, PIK3CD or PIK3R1 gene mutations cause activated PI3K-delta syndrome (APDS), a primary immunodeficiency disorder. APDS is somewhat recently understood, only being officially discovered in 2013. While doctors estimate that around 200 patients have been diagnosed thus far, the true incidence is still unknown.

APDS is inherited in an autosomal dominant fashion, meaning patients must only inherit one defective gene to be affected. Normally, PIK3CD codes for the production of the p110 delta protein. This protein impacts T cell and B cell growth, division, and proliferation. Thus, gene mutations cause naive (short-lived) cell development, causing patients to have low T and B cell levels. Because APDS is still not fully understood, the symptoms below cannot be considered a comprehensive list. However, known symptoms include:

  • Frequent and recurrent infections, often in the ears, lungs, and sinuses
    • Note: Bronchiectasis may also occur, as may a number of viral infections.
  • Clumped white blood cells which can cause solid masses in the intestines and airways
  • Lymphopenia (low levels of white blood cells)
  • Swollen lymph nodes
  • Increased risk of B-cell lymphoma

Treatment is still developing. Current standards of treatment include antibiotics (to fight infections), antiviral therapy, stem cell transplantation, and immunoglobulin replacement therapy. Additionally, the diagnostic process is still changing and strengthening as well. As of March 2021, Pharming and Invitae Corporation (“Invitae”) are working together on navigateAPDS to help with easier and faster APDS diagnosis. 

Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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