Will Fabhalta settle as a PNH treatment option in Korea?

An oral agent for Paroxysmal Nocturnal Hemoglobinuria

Novartis Korea undergoes reimbursement listing process for Fabhalta

Mechanistic limitations of existing C5 inhibitors such as Soliris exist

Whether another PNH treatment option will be born is gaining attention in Korea.

 

According to industry sources, Novartis Korea has submitted a reimbursement application for its oral paroxysmal nocturnal hemoglobinuria (PNH) treatment Fabhalta (iptacopan).

 

PNH is a rare disease with an estimated incidence of 1.5 per million people worldwide.  The treatment of this disease has historically relied on C5 inhibitors.

 

Soliris (eculizumab) was first approved in Korea in 2010 and Ultomiris (ravulizumab) was approved in 2022 for PNH.

 

Both are C5 inhibitors that inhibit the terminal C5 in the alternative pathway of the complement system involved in the body's immunity and are injected intravenously.

 

However, in April last year, Empaveli (pegcetacoplan), a subcutaneous injectable that binds to C3 and C3b and inhibits the complement chain reaction, was approved, followed in August by Fabhalta, an oral factor inhibitor.

 

Mechanistic limitations of C5 inhibitors, ‘extravascular hemolysis’ PNH begins with a genetic deficiency in red blood cells, which leads to intravascular hemolysis (IVH) and extravascular hemolysis (EVH).

 

Such type of hemolysis can soon lead to thrombosis and bone marrow failure, which can be life-threatening.

 

This is why it is important to control hemolysis to treat PNH, and while the current standard of care for PNH, C5 inhibitors, reduce the risk of thromboembolism by controlling intravascular hemolysis, they have limitations in limiting extravascular hemolysis.

 

This is why the reimbursement of factor B inhibitor Fabhalta is gaining interest.

 

Factor B is an alternative pathway upstream of C5, as well as C3 and C3b, and its inhibition can comprehensively control not only IVH but also EVH.

 

In fact, Fabhalta has shown efficacy in treatment-naïve patients.

 

In the APPOINT-PNH study on treatment-naïve PNH patients, 19 of 33 patients achieved hemoglobin levels of 12 g/dL or higher without red blood cell transfusions.

 

In addition, 92% of patients had shown a clinically significant increase in hemoglobin levels of 2 g/dL or more, and 63% of patients sustained a hemoglobin level of 12 g/dL or higher without transfusion.

 

Over the 24-week study period, hemoglobin levels continued to increase, with normalized hemoglobin levels reached at week 20 and sustained through week 24.

 

In addition, 98% of patients overcame transfusion dependency.

 

“When C5 inhibitors first appeared, experts said they brought a paradigm shift in the treatment of PNH,” said Dr.

 

Junho Jang, Dr.

 

Jun Ho Jang, Professor of Medicine, Department of Hematology-Oncology, Samsung Medical Center.

 

“However, C5 inhibitors still have limitations in controlling extravasation hemolysis (EVH).” He added, “Fabhalta represents another paradigm shift in the treatment of PNH.

 

Its mechanism of action, which inhibits factor B, involves factor B at the top of the alternative complement pathway, which can control both intravascular and extravascular hemolysis.

 

It has shown encouraging results in clinical trials.”