‘Oral drugs can address the unmet PNH treatment needs’

Novartis Korea holds conference to celebrate the approval of Fabhalta in Korea on the 25th

Unmet demand exists with C5 inhibitors...'extravasation hemolysis' is a concern

Fabhalta shows effect even in patients who failed existing treatments..."overcomes the side effect issue”

Dr.

 

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

The paroxysmal nocturnal hemoglobinuria (PNH) market, which has been dominated by AstraZeneca's Soliris and Ultomiris, has seen the introduction of the oral drug Fabhalta.

 

Experts believe that Fabhalta’s use will increase in the future as it has been shown to reduce anemia and blood transfusions compared to existing treatments.  On the 25th, Novartis Korea held a press conference for specialized journalists in Samseong-dong, Seoul, to celebrate the approval of Fabhalta in Korea.

 

Fabhalta was approved in August as the first oral treatment for PNH.  PNH is a rare and life-threatening disease caused by the destruction of red blood cells in the blood vessels, leading to symptoms of bloody urine and complications such as acute kidney failure.

 

The disease is estimated to affect approximately 1.5 people per million worldwide.  Its incidence is higher in East Asian countries such as Korea, China, and Japan than in Western countries.

 

The number of PNH patients in Korea is expected to have approximately doubled from 260 in 2010 to 504 in 2023, with the number still on the rise.

 

Fabhalta is a factor B inhibitor that acts proximally in the immune system's alternative complement pathway and has a comprehensive mechanism of action that controls red blood cell destruction.  Previously, PNH has been treated with C5 inhibitor drugs, including Soliris and Ultomiris.

 

However, while C5 inhibitors reduce the risk of thromboembolism by controlling intravascular hemolysis, they may not completely inhibit extravascular hemolysis.

 

Up to 50% of patients on C5 inhibitors experience extravascular hemolysis, which is a major contributor to the development of persistent anemia.

 

In addition, approximately 80% of PNH patients treated with C5 inhibitors have had an incomplete response to treatment, to the extent that they required transfusions or experienced anemia.  Fabhalta has been shown to be effective in patients both on and off C5 inhibitors.  The drug’s efficacy was confirmed through the Phase III APPLY-PNH trial in patients with residual anemia despite prior anti-C5 treatment who switched to Fabhalta and the Phase III APPOINT-PNH study in complement inhibitor-naïve patients.

 

Trial results showed that 82.3% of anti-C5-experienced Fabhalta patients, 0% of anti-C5-treated patients, and 77.5% of complement inhibitor-naïve patients showed a sustained increase of hemoglobin levels of 2 g/dLa or higher from baseline in the absence of transfusions.

 

The patients’ hemoglobin level was maintained in the 48-week extension study.

 

The study showed that patients who continued to take C5 inhibitors had hemoglobin levels similar to those of the initial switch group when they switched to Fabhalta at Week 24, and the fatigue score returned to those of healthy individuals in the Fabhalta arm.  In terms of safety, there were no treatment-related adverse events with Fabhalta that required treatment discontinuation.

 

The incidence of clinical breakthrough hemolysis was significantly lower with Fabhalta compared to C5 inhibitors, and headache, nausea, and diarrhea occurred but were resolved within 1 week.  An advantage of Fabhalta is its formulation.

 

As an oral formulation, the drug offers better dosing convenience over existing intravenous formulations like Soliris and Ultomiris.

 

Currently, Soliris (a 4-hour infusion once every 2 weeks) and Ultomiris (a 5.5-hour visit once every 8 weeks) require an in-person visit for their administration in the hospital.  The introduction of C5 inhibitors has significantly improved the treatment of PNH, but there is an unmet need amongst patients who are unable to benefit from the use of C5 inhibitors or experience side effects,” said Dr.

 

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

 

”Up to 82% of patients do not achieve normal hemoglobin levels with C5 inhibitors, which can lead to anemia and blood clots.  “ “Fabhalta targets both intravascular and extravascular hemolysis.

 

Its strength lies in its ability to normalize hemoglobin and LDH levels,” added Jang.

 

“In addition, switching from existing therapies to Fabhalta can improve patients’ quality of life by reducing fatigue, and can help patients overcome transfusion dependency.”