Summary of safety profile The most commonly reported adverse reactions during leniolisib treatment were headache (32%), vomiting (16%), weight increase (13%), and alopecia (11%). Based on laboratory data from the clinical studies, 33% of patients experienced a decrease in neutrophil counts.
Tabulated list of adverse reactions The safety of leniolisib was evaluated in 38 adolescent and adult patients with APDS who participated in the placebo-controlled portion of Study 2201, and an open label safety study. Thirty-seven of 38 patients received leniolisib 70 mg orally twice daily for at least 60 weeks and 84% were exposed for 108 weeks or longer.
Median duration of leniolisib treatment was approximately 4 years, and 10 patients had more than 5 years of leniolisib exposure. The following list of adverse reactions is based on experience from clinical trials and on postmarketing experience.
Adverse reactions in Table 1 are listed by system organ class and frequency. Frequencies are defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), and rare (≥ 1/10 000 to < 1/1 000), and not known (cannot be estimated from the available data).
Within each frequency grouping, adverse reactions are presented in order of decreasing frequency. Table 1 Adverse reactions System organ class Adverse reaction Frequency Immune system disorders Hypersensitivity* Not known Nervous system disorders Headache Very common Gastrointestinal disorders Vomiting Very common Dyspepsia Common Skin and subcutaneous tissue disorders Alopecia Very common Atopic dermatitis** Common Rash Common 7 System organ class Adverse reaction Frequency General disorders and administration site conditions Fatigue Common Investigations Weight increased Very common Neutrophil count decreased Very common *Hypersensitivity: including itching, skin redness, hives, rash, difficulty breathing or swallowing (from post-marketing use of Joenja) **Atopic dermatitis: including dermatitis atopic and eczema Description of selected adverse reactions Neutrophil count decreased Seven (33%) patients receiving leniolisib developed a transient absolute neutrophil count (ANC) between 500 and 1500 cells/μL.
No patients developed an ANC < 500 cells/μL and there were no reports of infection associated with neutropenia. One case of Grade 3 neutrophil count decrease considered related to leniolisib was reported. Hypersensitivity Hypersensitivity reactions have been identified during post-marketing use of Joenja.
Paediatric population Thirteen patients aged 12 to 17 were treated with leniolisib in the clinical trials. Frequency, type, and severity of adverse reactions were similar to adults. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.
It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.