New PNH drugs introduced into AstraZeneca’s reign

AstraZeneca raises its defense in the market amid the introduction of new drugs

Handok’s Empaveli passes DREC review…the drug’s insurance reimbursement in sight

Fabhalta’s introduction imminent…will compete with Ultomiris, Soliris

Competition is in full swing in the paroxysmal nocturnal hemoglobinuria (PNH) market, which is currently dominated by AstraZeneca's treatments such as Soliris and Ultomiris, with the introduction of new drugs that have new mechanisms of action soon to emerge in the market.

 

Recently, Handok's Empaveli is nearing reimbursement in Korea, and Novartis has filed for domestic marketing authorization of its new drug Fabhalta.

 

Amid the introduction of such new drugs, AstraZeneca is defending its market by receiving approval for Voydeya, which is used as an adjuvant therapy with Soliris and Ultomiris.

 

According to industry sources on the 6th, Handok's Empaveli (pegcetacoplan) was approved adequate for reimbursement by the Health Insurance Review and Assessment Service's Drug Reimbursement Evaluation Committee.

 

Empaveli passed the committee 2 months after being approved in May, ahead of drug pricing negotiations with the National Health Insurance Service.

 

New PNH drug introduced by Handok in Korea

Empaveli is a treatment for paroxysmal nocturnal hemoglobinuria (PNH) developed by the U.S.

 

company Apellis.

 

The drug’s license in countries other than the U.S.

 

is owned by the Swedish Orphan Biovitrum (Sobi).

 

Handok entered into a strategic partnership with Sobi in October last year to introduce Empaveli in Korea.

 

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 renal failure.

 

Empaveli is the first PNH treatment to target the C3 protein.

 

By blocking C3 cleavage, the drug prevents intravascular and extravascular hemolysis.

 

Empaveli’s efficacy was confirmed over Soliris (eculizumab) in the Phase III PEGASUS trial.

 

In the study, the level of lactate dehydrogenase (LDH), a marker of intravascular hemolysis, remained below 1.5 times the upper limit of normal for 48 weeks in the Empaveli treatment arm.

 

The percentage of patients who remained transfusion-free for 16 weeks was also higher in the Empaveli treatment arm (85%) compared with the Soliris arm (15%).

 

The efficacy of Empaveli was also confirmed in the PRINCE trial in treatment-naïve PNH patients.

 

After 26 weeks of follow-up, 85.7% of patients in the Empaveli arm showed stable hemoglobin levels, and LDH levels were well controlled to normal levels in the Empaveli arm.

 

In addition to Empaveli, other new drugs from multinational pharmaceutical companies are also preparing to enter Korea.

 

Novartis recently submitted a new drug application (NDA) for its PNH drug Fabhalta (iptacopan) in Korea.

 

Novartis

Fabhalta is a factor B inhibitor that acts proximally in the immune system's alternative complement pathway, providing comprehensive control of red blood cell destruction.

 

The advantage of Fabhalta is its formulation.

 

As an oral agent, Fabhalta offers dosing convenience compared to the existing intravenous formulations like Soliris and Ultomiris (ravulizumab).

 

Fabhalta’s efficacy was confirmed in patients who failed complement C5 inhibitor treatment or had received no prior therapy.

 

Study results showed that 82% of patients in the Fabhalta arm achieved a 2g/dL increase in hemoglobin at week 24 without red blood cell transfusions.

 

In addition, Roche's C5 complement inhibitor Piasky (crovalimab) also showed clinical benefit.

 

Piasky demonstrated non-inferiority to Soliris across multiple endpoints, including the rate of abrupt hemolysis and the rate of hemoglobin level stabilization.

 

AZ Voydeya approved in Korea as add-on therapy to Soliris and Ultomiris The PNH market has been dominated by AstraZeneca, which owns new C5 complement inhibitor class drugs, including Soliris and Ultomiris.

 

However, the introduction of other new drugs is expected to increase competition in the area.

 

AstraZeneca will defend the market with its oral factor D inhibitor, Voydeya add-on therapy.

 

Voydeya was approved in Korea on March 28 as an add-on therapy for PNH patients with symptoms or signs of extravascular hemolysis (EVH) who are using Soliris and Ultomiris.

 

Complement C5 inhibitors are expected to complement the development of EVH and anemia experienced by some patients with PNH.

 

Voydeya has received the Breakthrough Therapy designation in the U.S.

 

and PRIority MEdicines (PRIME) status in Europe.

 

Voydeya's domestic approval was based on the Phase III ALPHA trial.

 

In the trial, Voydeya met its primary endpoint of change in hemoglobin level in patients on C5 complement inhibitors that experience EVH.

 

Specifically, Voydeya demonstrated an improvement compared with placebo in the primary endpoint of change in hemoglobin concentration from baseline to week 12.

 

Voydeya also achieved a 60% increase in hemoglobin of 2g/dL or greater at Week 12 without transfusion compared to 0% with placebo.

 

In terms of safety, the most common treatment-emergent adverse events were headache and diarrhea.