Drug Trials Snapshots: JOENJA

HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug, and whether there were differences among sex, race, age, and ethnic groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.

LIMITATIONS OF THIS SNAPSHOT:
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your healthcare provider about the benefits and risks of a drug.

Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the JOENJA Prescribing Information for all of the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information).

Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).

JOENJA (leniolisib)
jo en' jah
Pharming Technologies BV
Original Approval date: March 24, 2023

---

DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

JOENJA is a kinase inhibitor that is used to treat activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome (APDS) in adult and pediatric patients 12 years of age and older who weigh at least 45 kg.

APDS is an inherited disease that impacts the immune system. APDS often causes a decrease in T and B cells that fight infection as well as an increase in lymph node size.

How is this drug used?

JOENJA is a tablet taken by mouth every 12 hours.

Who participated in the clinical trials?

The FDA approved JOENJA based on evidence from a clinical trial of 31 patients with APDS. The trial was conducted at 10 sites in 9 countries in Italy, the United States, United Kingdom, Czech Republic, Netherlands, Ireland, Belarus, Russia, and Germany.

How were the trials designed?

JOENJA was evaluated in one placebo-controlled clinical trial of 31 patients with APDS. Patients were randomized 2:1 to receive either JOENJA 70 mg (N=21) or placebo (N=10) twice a day for 12 weeks. The coprimary efficacy endpoints were a reduction in the size of lymph nodes and the increase in percentage of naïve B cells. Neither the patients nor the investigators knew which treatment was being given until after the trial was completed.

Investigators measured the size of lymph nodes before the first dose of JOENJA or placebo and after the end of the study by imaging. Blood samples were taken from patients during the 12 week treatment period to record the number of naïve B cells in the patient’s blood.

How were the trials designed?

The efficacy and safety of JOENJA was evaluated in the placebo-controlled portion of Study 2201 (NCT02435173), a 12-week, blinded, randomized, placebo-controlled study in 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. Patients were randomized to receive JOENJA 75 mg twice daily or placebo for 12 weeks. The primary efficacy endpoints were the reduction in size of lymph nodes and increase in naïve B cells.

DEMOGRAPHICS SNAPSHOT

Figure 1 summarizes how many males and females were enrolled in the clinical trial used to evaluate the efficacy of JOENJA.

Figure 1. Baseline Demographics by Sex

Source: Adapted from FDA Review

Figure 2 summarizes the percentage of patients by race enrolled in the clinical trial used to evaluate the efficacy of JOENJA.

Figure 2. Baseline Demographics by Race

Source: Adapted from FDA Review

Figure 3 summarizes the percentage of patients by age enrolled in the clinical trial used to evaluate the efficacy of JOENJA.

Figure 3. Baseline Demographics by Age

Source: Adapted from FDA Review

Figure 4 summarizes the percentage of patients by ethnicity enrolled in the clinical trial used to evaluate the efficacy of JOENJA.

Figure 4. Baseline Demographics by Ethnicity

Source: Adapted from FDA Review

Who participated in the trials?

Table 1 summarizes demographics of patients in the clinical trial.

Table 1. Baseline Characteristics and Disease Characteristics

Parameter	JOENJA N=21	Placebo N=10
Age1, years
Mean (SD)	22.2 (10.00)	26.7 (13.43)
Min, max	12, 54	15, 48
Age group, years, n (%)
<18	8 (38)	4 (40)
≥18	13 (62)	6 (60)
Sex, n (%)
Male	11 (52)	4 (40)
Female	10 (48)	6 (60)
Race, n (%)
Asian	1 (5)	1 (10)
Black or African American	1 (5)	1 (10)
White	18 (86)	7 (70)
Other	1 (5)	1 (10)
Ethnicity, n (%)
Hispanic or Latino	0	1 (10)
Not Hispanic or Latino	14 (67)	7 (70)
Not reported	7 (33)	2 (20)
Disease characteristics, n (%)
APDS 1 (PIK3CD variant)	16 (76)	9 (90)
APDS 2 (PIK3R1 variant)	5 (24)	1 (10)
Concomitant glucocorticoids	12 (57)	6 (60)
Concomitant IgG	14 (67)	7 (70)
Previous rapamycin or sirolimus use	4 (19)	3 (30)

Source: JOENJA Prescribing Information
¹ Patient age from study Day -4 up to initial JOENJA dosing
Abbreviations: APDS, activated phosphoinositide 3-kinase delta (PI3Kδ) syndrome; IgG, immunoglobulin G; SD, standard deviation

What are the benefits of this drug?

In patients with APDS, JOENJA increased the percentage of B cells important in fighting infections and decreased the size of lymph nodes.

What are the benefits of this drug (results of trials used to assess efficacy)?

The efficacy of JOENJA was evaluated in the placebo-controlled portion of Study 2201, a 12-week, blinded, randomized, placebo-controlled study in adult and pediatric patients 12 years of age and older with confirmed APDS. Patients were randomized 2:1 to receive either JOENJA 70 mg (N=21) or placebo (N=10) twice a day for 12 weeks. Table 2 summarizes efficacy results for the evaluated patients in Study 2201. Lymph node size and percentage of naïve B cells compared to placebo were the two primary study endpoints.

Table 2. Coprimary Endpoints in Change From Baseline at Week 12

Endpoint	JOENJA N=21	Placebo N=10
Log10-transformed SPD of index lesions (excluding patients with 0 lesions at baseline)a
nb	18	8
Baseline mean (SD)	3.03 (0.42)	3.05 (0.39)
LS mean change from baseline (SE)	-0.27 (0.04)	-0.02 (0.05)
LS mean difference from placebo (95% CI)	-0.25 (-0.38, -0.12)
p-value	0.0006
Percentage of naïve B cells out of total B cells (patients with <48% of naïve B cells at baseline)c
nd	8	5
Baselinee mean (SD)	27.16 (13.16)	30.51 (7.97)
LS mean change from baseline (SE)	37.39 (5.34)	0.09 (6.66)
LS mean difference from placebo (95% CI)	37.30 (24.06, 50.54)
p-value	0.0002

Source: JOENJA Prescribing Information
Note: The LS mean change from baseline, difference in LS mean change from baseline between JOENJA and placebo and its p-value were obtained from an Analysis of Covariance model with treatment, glucocorticoids use and immunoglobulin replacement therapy at baseline, and baseline measurement as covariates.
^a Change in index lesion size was measured using the log10-transformed sum of the product of diameters (SPD) of the largest lymph nodes (maximum of six) identified as per the Cheson criteria on computed tomography (CT) or magnetic resonance imaging (MRI).
^b The analysis excluded two patients from each treatment group due to protocol deviations and one JOENJA patient having complete resolution of the index lesion identified at baseline.
^c Cell surface markers used to distinguish naïve B cells on flow cytometry were CD19+ CD27- CD10-.
^d The analysis excluded two patients from each treatment group due to protocol deviations, five JOENJA patients and three placebo patients with ≥48% naïve B cells at baseline, five JOENJA patients with no Day 85 measurement, and one JOENJA patient with no baseline measurement.
^e Baseline is defined as the arithmetic mean of the baseline and Day 1 values when both were available, and if either value was missing, the existing value was used.
Abbreviations: CI, confidence interval; LS, least-squares; n, number of patients in the analysis; SD, standard deviation; SE, standard error; SPD, sum of product diameters

Were there any differences in how well the drug worked in clinical trials among sex, race and age?

• Sex: JOENJA worked similarly in males and females.
• Race: Most of the patients were White. Differences in how well the drug worked among races could not be determined because of the small number of patients in other races.
• Age: All patients were between 12 to 54 years of age; therefore, differences in how well the drug worked among older age groups could not be determined. JOENJA worked similarly between patients younger and older than 18 years of age.

Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?

Although numbers within each subgroup were small, the treatment effect for the coprimary endpoints were preserved across age and sex subgroups. Because the proportion of subjects other than White in the study was small, it is difficult to draw any conclusions from the subgroup analysis by race; however, there were no apparent differences.

Table 3. Change From Baseline at Week 12 in Log₁₀ Transformed SPD of Index Lesions by Subgroups

Subgroup (n[J], n[p])	LS Mean Change From Baseline		LS Mean Difference From Placebo (95% CI)
	JOENJA	Placebo
Sex
Female (9, 5)	-0.21	-0.07	-0.13 (-0.28, 0.01)
Male (9, 3)	-0.34	0.16	-0.50 (-0.64, -0.36)
Age, years
<18 (7, 3)	-0.37	-0.10	-0.27 (-0.57, 0.02)
≥18 (11, 5)	-0.25	0.06	-0.31 (-0.48, -0.14)

Source: Adapted from FDA Review
Abbreviations: CI, confidence interval; LS, least-squares; n[J], number of patients in subgroup in the JOENJA treatment arm; n[p], number of patients in subgroup in the placebo treatment arm; SPD, sum of the product of diameters

Table 4. Change From Baseline at Week 12 in Proportion of Naïve B Cells Out of Total B Cells by Subgroups

Subgroup (n[J], n[p])	LS Mean Change From Baseline		LS Mean Difference From Placebo (95% CI)
	JOENJA	Placebo
Sex
Female (3, 2)	25.51	-2.94	28.45 (NE)
Male (5, 3)	35.01	-2.75	37.77 (23.07, 52.47)
Age, years
<18 (4, 2)	44.53	-16.53	61.06 (12.59, 109.53)
≥18 (4, 3)	28.40	-1.07	29.47 (15.99, 42.95)

Source: Adapted from FDA Review
Abbreviations: CI, confidence interval; LS, least-squares; NE, not estimable; n[J], number of patients in subgroup in the JOENJA treatment arm; n[p], number of patients in subgroup in the placebo treatment arm

What are the possible side effects?

The most common adverse reactions (>10%) were headache, sinusitis, and atopic dermatitis. Adverse reactions reported by two or more patients treated with JOENJA and more frequently than placebo are summarized in Table 5.

What are the possible side effects (results of trials used to assess safety)?

Table 5. Adverse Reactions Reported by Two or More JOENJA-Treated Patients and More Frequently Than Placebo

Adverse Reactions	JOENJA N=21 n (%)	Placebo N=10 n (%)
Headache	5 (24)	2 (20)
Sinusitis	4 (19)	0
Dermatitis atopic1	3 (14)	0
Tachycardia2	2 (10)	0
Diarrhea	2 (10)	0
Fatigue	2 (10)	1 (10)
Pyrexia	2 (10)	0
Back pain	2 (10)	0
Neck pain	2 (10)	0
Alopecia	2 (10)	0

Source: JOENJA Prescribing Information
¹ Dermatitis atopic: including dermatitis atopic and eczema
² Tachycardia: including tachycardia and sinus tachycardia

Were there any differences in side effects of the clinical trials among sex, race, and age?

• Sex: The occurrence of side effects was slightly higher in females than in males. There were no major differences in the patterns or types of side effects between females and males. Because of limited data, this difference may be due to chance.
• Race: Most of the patients were White. Differences in the occurrence of side effects among races could not be determined because of the small number of patients in other races.
• Age: All patients were 12 to 54 years of age; therefore, differences in the occurrence of side effects among older age groups could not be determined. The occurrence of side effects was similar between patients younger and older than 18 years of age.

Were there any differences in side effects of the clinical trials among sex, race, and age groups?

Although the number of subjects within each subgroup limits the interpretation of these analyses, there were no apparent differences in the safety profile of JOENJA by age group, sex, race.

GLOSSARY

CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.

LINK TO DRUG PACKAGE INSERT

Back to Drug Trials Snapshots