How does Empaveli compare to Soliris?

Empaveli is a brand (trade) name for pegcetacoplan which is a PEGylated 40kDa polyethylene glycol linear small molecule that acts as a C3 complement inhibitor. It helps stop both intravascular hemolysis (IVH) (the destruction of red blood cells in the circulation) and extravascular hemolysis (EVH) (the breakdown of red blood cells in the spleen, bone marrow, or liver by macrophages). Empaveli is the only treatment that targets C3 to help prevent both forms of red blood cell destruction (IVH and EVH). Empaveli is only used to treat paroxysmal nocturnal hemoglobinuria (PNH) and it is more effective than Soliris at treating PNH because it works higher up the complement cascade. It is given by subcutaneous infusion and people can be taught how to self-administer the Empaveli Injector at home.

Soliris is a brand (trade) name for eculizumab which is a monoclonal antibody that specifically binds to the complement protein C5 with high affinity, preventing it from splitting into C5a and C5b, which stops generation of the terminal complement complex C5b-9. This helps to stop IVH, but not EVH. Solaris may be used to treat adults and children with PNH or atypical hemolytic uremic syndrome and certain adults with generalized Myasthenia Gravis or neuromyelitis optica spectrum disorder. Soliris is given by infusion under the guidance of a healthcare professional every 2 weeks (after the initial dosing schedule) but most patients are encouraged to switch from Soliris to Ultomaris which only requires 7 infusions in adults a year.

Is there a difference in side effects between Empaveli and Soliris?

Empaveli is more likely than Soliris to cause:

• injection site reactions
• and diarrhea

but less likely than Soliris to cause:

• breakthrough hemolysis
• headache
• and fatigue.

There were no cases of meningitis in either group.

71% of people receiving Empaveli experienced normalization of their lactate dehydrogenase levels (LDH) levels within the first 4 weeks that persisted for 16 weeks in one trial, compared to only 15% receiving Soliris.

What are Empaveli and Soliris used for?

Empaveli and Soliris are prescription medicines approved to treat adults with paroxysmal nocturnal hemoglobinuria (PNH).

PNH is a rare acquired, life-threatening disease of the blood that is characterized by the destruction of red blood cells (hemolytic anemia), blood clots (thrombosis), and impaired bone marrow function.

Soliris may also be used to treat:

• atypical hemolytic uremic syndrome (adults and children)
• generalized Myasthenia Gravis who are anti-acetylcholine receptor antibody-positive (adults)
• neuromyelitis optica spectrum disorder who are anti-aquaporin-4 antibody positive (adults).

Empaveli is only approved to treat PNH.

How are Empaveli and Soliris administered?

Empaveli is administered by subcutaneous (just under the skin) infusion and Soliris is given by intravenous infusion (into a vein).

People can be taught how to self-administer Empaveli, using the Empaveli injector which is a compact, wearable, circular device that is placed on your stomach at least 1 inch from your belly button or previous injection site. This allows the person to be mobile and continue light daily activities without having to sit still waiting for the infusion to finish. Empaveli can also be given subcutaneously by a healthcare provider as an infusion into a clear area of skin on a person’s stomach (avoiding the belly button), top of the thighs, hips, or upper arms.

Soliris is usually given by a healthcare professional.

Empaveli is administered every two weeks and Soliris is given weekly for the first 5 weeks, then two weekly thereafter.

Most patients who started on Soliris are encouraged to switch to Ultomaris, which is made by the same company. Ultomaris contains the same ingredient as Soliris (eculizumab) but as a long-acting formulation which only needs to be given 7 times a year (after the initial starting dose) in adults and children over44 lb (20 kg). People switching from Soliris to Ultomiris should receive their starting dose of Ultomiris 2 weeks after the last dose of Soliris. Most Ultomaris infusions take less than 1 hour.

What do Empaveli and Soliris contain?

Empaveli contains pegcetacoplan and Soliris contains eculizumab.

How do Empaveli and Soliris work?

Both Empaveli and Soliris affect the complement system, which is a part of the immune system that enhances (or complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and attack the pathogen's cell membrane, but they each work in a slightly different way.

Empaveli works higher in the complement system than Soliris, binding to complement protein C3 and preventing it from splitting into C3a and C3b. It is a PEGylated 40kDa polyethylene glycol linear small molecule. Empaveli helps stop both IVH (the destruction of red blood cells in the circulation) and EVH (the breakdown of red blood cells in the spleen, bone marrow, or liver by macrophages). Empaveli is the only treatment that targets C3 to help prevent both forms of red blood cell destruction (IVH and EVH).

Soliris is a monoclonal antibody that binds to complement protein C5 which is further down the complement system, preventing it from splitting into C5a and C5b, which stops generation of the terminal complement complex C5b-9. This helps to stop IVH, but not EVH.