Expanded clinical use of orphan drug 'Joenja' in children

Approval for children aged 4 and older

The Central Pharmaceutical Affairs Advisory Committee (CPAC) seeks consultation on the approval of the clinical trial drug from a foreign country for therapeutic use

Currently available drug is 70 mg formulation, 10 mg and 30 mg tablets will be provided to children

Product photo of Joenja.

The administration·dosage in children for a clinical trial of 'Joenja (leniolisb),' an APDS treatment designated as an orphan drug in South Korea, is expected to be expanded.

 

The meeting record of the Central Pharmaceutical Affairs Advisory Committee (CPAC), released by the Ministry of Food and Drug Safety (MFDS) on December 4, indicates that there has been a consultation regarding the application for approval of a medication on clinical trial intended for therapeutic use, which is currently undergoing clinical trials in a foreign country.

 

It was reported that the medication is Joenja, a treatment for activated phosphoinositide 3-kinase delta syndrome (APDS).

 

In June, Joenja was designated as an orphan drug.

 

APDS is caused by mutations in one of the genes encoding PIK3CD or PIK3R1 that is needed for the development and function of immune cells.

 

The disease occurs in 1 in 1-2 million people.

 

Patients exhibit autoimmunity and inflammatory symptoms.

 

Symptoms include ears infections, paranasal infections, and upper·lower respiratory infections.

 

Lymph nodes or the spleen may enlarge, and patients have increased risk of developing cancer, such as lymphoma.

 

The approval of Joenja was based on the results of multinational, triple-blinded, placebo-controlled, randomized clinical 2/3 trials.

 

The clinical trial involved 31 APDS patients over 12 years old.

 

At the recent CPAC meeting, discussions were held on the age range eligible for approval based on pediatric administration·dosage and predicted through pharmacokinetic (PBPK) modeling data and case studies from a compassionate use program (10 patients).

 

The CPAC concluded that approval could be granted for patients aged four years and older, with further discussions required for those under four.

 

Regarding the PBPK modeling data, one committee member stated, "Metabolism is proportional to body weight and liver volume, with differences of about 20% observed even among adults, making application in children reasonable." "However, since kidney function, liver function, and body composition become similar to adults only after two, predicting results for patients under two years old is challenging." Most committee members state that the submitted modeling document presents no significant issue.

 

One committee member commented, "FDA reports indicate that medication use in ages 4-11 will not pose any problem based on the modeling result.

 

However, the applications below the age of 4 or 2 must need further discussion." Another committee member stated, "The CYP cell maturity is similar after age 2, larger liver size and hepatic clearance.

 

We believe that this has been incorporated in the modeling." Once patients start taking medication, they are likely to continue treatment.

 

Therefore, concerns have arisen that administration should only begin after safety results are reviewed.

 

However, the committee chair noted that data collection could be challenging since the target population comprises children with rare diseases.

 

Regarding this, "The medication has been designated as an orphan drug in both the U.S.

 

and Korea, with four additional approved cases," the MFDS stated.

 

"We need consultation on whether the clinical trial data from U.S.

 

approval, submitted as evidence of safety and efficacy, along with the modeling data and case studies from 10 patients, can substitute for therapeutic confirmatory or exploratory clinical trial results." Consequently, it was concluded that CPAC must give a green light, as the unapproved status in South Korea and CPAC's opposition to access would deny Korean patients treatment opportunities.

 

Meanwhile, since the currently available 70 mg product is a film-coated tablet that children may be unable to swallow, the company plans to provide the medication in 10 mg and 30 mg tablets.