FDA Greenlights First Drug for Rare Immunodeficiency Disease

The FDA approved leniolisib (Joenja) on Friday as the first treatment indicated for activated phosphoinositide 3-kinase delta syndrome (APDS), a rare genetic disorder that causes progressive primary immunodeficiency.

Leniolisib, an oral small molecule PI3K delta inhibitor, is indicated for use in patients who are age 12 and older. It is administered orally, at 70 mg twice daily for 12 weeks among patients weighing at least 45 kg (99 lb).

This approval "offers to transform the treatment pathway for patients and families affected by this rare disease," said Eveline Wu, MD, of the University of North Carolina at Chapel Hill, in a statement from the drugmaker, Pharming Group. "This approval means that they will, for the first time, have access to an approved treatment, which has the potential to change the standard of care for the patient population suffering from APDS."

The rare genetic condition, also called PASLI disease, was identified in 2013. It affects one to two per million people worldwide who have genetic variations in the PIK3CD or PIK3R1 genes, which are vital for immune function. The disease causes infections in the ears, sinuses, upper and lower respiratory tract, usually starting in infancy. Those with APDS are susceptible to swollen lymph nodes or an enlarged spleen along with autoimmunity and inflammatory symptoms. APDS patients are also at higher risk for lymphoma and other blood cancers.

The disease can be detected with genetic testing.

In a phase II/III randomized controlled trial involving 31 patients, leniolisib significantly reduced the size of patient lymph nodes by day 85 and increased B cells counts by 37% (P=0.0002) compared with placebo, meeting the trial's co-primary endpoints and indicating a correction of the underlying immune defect.

Adverse reactions to the drug reported in more than 10% of trial participants included headache, sinusitis, and atopic dermatitis.

The drug should not be taken by pregnant women, as it comes with potential risk to the fetus. Women treated with leniolisib should use highly effective methods of contraception during treatment and for 1 week after the last dose, warns the drug label.

In addition, patients with moderate to severe liver failure should not take leniolisib, and patients should be aware that live attenuated vaccinations may be less effective if taken while receiving leniolisib.

During the trial, there were seven patients (33%) who developed an absolute neutrophil count between 500 and 1,500 cells/μL, but none dropped below 500 cells/μL. No infections were reported in association with neutropenia.

The drugmaker expects leniolisib to be available to U.S. APDS patients by April.

The approval also provides hope beyond just the APDS patients and families, suggested Vicki Modell, co-founder of the Jeffrey Modell Foundation, a non-profit organization focused on primary immunodeficiency disorders.

"The FDA approval of a treatment option for one of the more than 450 primary immunodeficiencies is also a key moment for the broader primary immunodeficiency community," she said in the Pharming press release.

Comment