Effective Date

Date of Origin 

07-01-2024            

10-01-2023

Joenja®

(leniolisib)

Tablets

Treatment of activated phosphoinositide 3-kinase delta (PI3K-delta) syndrome (APDS) in adult and pediatric patients 12 years of age and older

1

Primary Immunodeficiencies

Primary immunodeficiencies (PIDs) are a group of inborn error disorders that cause immune dysfunction and manifest with increased susceptibility to infections. Many PIDs are monogenic diseases. To date, mutations in more than 300 genes have been shown to cause various PIDs. Activated phosphoinositide 3-kinase delta syndrome (APDS) is a PID that results from pathogenic variant mutations in either the PIK3CD gene (APDS1) or the PIK3R1 gene (APDS2). Both genes are important for the growth, survival and function of lymphocytes.(2,3,4,6)

Definitive diagnosis is made through genetic testing, which Pharming Healthcare Inc offers at no-charge (including counseling) for individuals who are suspected to carry a pathogenic variant in PIK3CD or PIK3R1. Patients may present in childhood or later in life with severe, persistent and recurrent bacterial and viral infections, bronchiectasis, lymphadenopathy, delayed development (e.g., speech, growth), and/or hepato- or splenomegaly. Additionally, patients may present with signs of autoimmune or inflammatory conditions, such as anemia, cytopenias, nodular lymphoid hyperplasia, enteropathy, glomerulonephritis, organ dysfunction.(5,7,8)

Before Joenja, the only treatments for APDS were focused on managing symptoms, with a combination of long-term immunoglobulin replacement therapy to help support the immune system, immunosuppressive medications to help with symptoms due to autoimmunity and inflammation, and daily antibiotics to help prevent infections before they happen.(2,3,5) Joenja is targeted at the actual problem (gain-of-function mutation in the PIK3CD disrupts normal development of immune cells; Joenja selectively inhibits a subunit of PI3K, which specifically reverses the pathophysiology of APDS in a molecularly targeted manner.(6,9)

Efficacy

Joenja (leniolisib) is an oral selective PI3K-delta inhibitor. In cell-based assays, Joenja inhibited the signaling pathways that lead to the dysregulation of B and T cells.(1)

The efficacy 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 PI3K-delta mutation with a documented variant in either PIK3CD or PIK3R1. Patients had nodal and/or extranodal lymphoproliferation, as measured by index nodal lesion selected by the Cheson methodology on CT or MRI and clinical findings and manifestations compatible with APDS (e.g., history of repeated oto-sino-pulmonary infections, organ dysfunction). Thirty-one patients were randomized 2:1 to receive either Joenja 70 mg (N=21) or placebo (N=10) twice a day for 12 weeks. The co-primary efficacy endpoints were improvement in lymphoproliferation as measured by a change from baseline in lymphadenopathy measured by the log10-transformed sum of product diameters and the normalization of immunophenotype as measured by the percentage of naïve B cells out of total B cells. Findings showed that leniolisib met the coprimary endpoints demonstrating a statistically significant reduction in index lymph node size (p=.006) and normalization of immunodeficiency (as evidenced by an increased proportion of naïve B cells from baseline; p=.002), compared with placebo.(1,6)

Safety

Joenja (leniolisib) has no FDA labeled contraindications for use.(1)

1

Joenja prescribing information. Pharming Technologies BV. March 2023. 

2

Singh A, Joshi V, Jindal AK, et al. An Updated Review on Activated PI3 Kinase Delta Syndrome (APDS). Genes Dis. 2020 Mar;7(1):67-74.

3

Michalovich D, Nejentsev S. Activated PI3 Kinase Delta Syndrome: From Genetics to Therapy. Front Immunol. 2018 Feb;9:369.

4

Ewertowska M, Grzesk E, Urbanczyk A, et al. Activated Phosphoinositide 3-Kinase Delta Syndrome 1 and 2 (APDS 1 and APDS 2): Similarities and Differences Based on Clinical Presentation in Two Boys. Allergy Asthma Clin Immunol. 2020 Apr;16:22.

5

Oh J. Activated Phosphoinositide 3-Kinase Delta Syndrome (APDS). National Organization of Rare Diseases (NORD). Last updated: April 2023. Available at: https://rarediseases.org/rare-diseases/activated-phosphoinositide-3-kinase-delta-syndrome-apds/

6

Rao VK, Webster S, Sediva A, et al. A Randomized, Placebo-Controlled Phase 3 Trial of the PI3K-delta Inhibitor Leniolisib for Activated PI3K-delta Syndrome. Blood. 2023 Mar;141(9):971-983.

7

International Patient Organization for Primary Immunodeficiencies (IPOPI). Primary Immunodeficiencies: APDS - Activated PI3K Delta Syndrome. 2020. Available at: http://www.immunodeficiencyuk.org/static/media/up/IPOPIADPS.pdf

8

All About APDS - Healthcare Professionals. Available at: https://allaboutapds-hcp.com/. Accessed December 2023.

9

Rao VK, Webster S, Dalm VASH, et al. Effective "Activated PI3K-Delta Syndrome"-Targeted Therapy with the PI3K-Delta Inhibitor Leniolisib. Blood. 2017 Nov;130(21):2307-2316.

Joenja

leniolisib phosphate tab

70 MG

M ; N ; O ; Y

N

Joenja

leniolisib phosphate tab

70 MG

60

Tablets

30

DAYS

Joenja

leniolisib phosphate tab

70 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Joenja

leniolisib phosphate tab

70 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Initial Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. ONE of the following:
   1. The requested agent is eligible for continuation of therapy AND ONE of the following:

1. The patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days OR
2. The prescriber states the patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days AND is at risk if therapy is changed OR
3. ALL of the following:
   1. The patient has a diagnosis of activated phosphoinositide 3-kinase (PI3K) delta syndrome (APDS) AND
   2. The patient has a variant in either PIK3CD or PIK3R1 AND
   3. If the patient has an FDA labeled indication, then ONE of the following:
      1. The patient’s age is within FDA labeling for the requested indication for the requested agent OR
      2. There is support for using the requested agent for the patient’s age for the requested indication AND
4. The patient's weight is 45 kg or greater AND
5. The prescriber has assessed the patient's baseline (prior to therapy with the requested agent) status of clinical manifestations of APDS (e.g., recurrent sinopulmonary infections, recurrent herpesvirus infections, lymphadenopathy, hepatomegaly, splenomegaly, nodular lymphoid hyperplasia, autoimmunity, cytopenias, enteropathy, bronchiectasis, organ dysfunction) AND
6. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., geneticist, immunologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
7. The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval:  6 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

Renewal Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. The patient has been previously approved for the requested agent through the plan’s Prior Authorization process [Note: patients not previously approved for the requested agent will require initial evaluation] AND
2. The patient has had improvements or stabilization with the requested agent (e.g., sinopulmonary infections, herpesvirus infections, lymphadenopathy, hepatomegaly, splenomegaly, nodular lymphoid hyperplasia, autoimmunity, cytopenias, enteropathy, bronchiectasis, organ dysfunction) AND
3. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., geneticist, immunologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
4. The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval:  12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria. 

Quantity limit for the Target Agent(s) will be approved when ONE of the following is met:

1. The requested quantity (dose) does NOT exceed the program quantity limit OR
2. ALL of the following:
   1. The requested quantity (dose) exceeds the program quantity limit AND
   2. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND
   3. The requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does NOT exceed the program quantity limit OR
3. ALL of the following:
   1. The requested quantity (dose) exceeds the program quantity limit AND
   2. The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND
   3. There is support of therapy with a higher dose for the requested indication

Length of Approval:  Initial up to 6 months; Renewal up to 12 months