PNH (paroxysmal nocturnal hemoglobinuria) is treated primarily with complement inhibitors, a class of drugs that block the immune system from destroying red blood cells. Several medications are now available, ranging from intravenous infusions given every few weeks to daily oral pills. The right choice depends on disease severity, how well you respond to initial treatment, and practical factors like whether you prefer injections or pills.
Not everyone diagnosed with PNH needs medication right away. Simply having a detectable PNH clone isn’t enough to start complement therapy. Treatment is reserved for people with symptomatic hemolysis, meaning your body is actively breaking down red blood cells at a rate that causes problems: severe anemia requiring transfusions, blood clots, kidney damage, abdominal pain crises, or other significant symptoms.
Terminal Complement Inhibitors
The first generation of PNH drugs work by blocking the final steps of the complement cascade, the part of your immune system responsible for punching holes in unprotected red blood cells. These drugs target a protein called C5, preventing the formation of the “membrane attack complex” that destroys cells.
Eculizumab was the first complement inhibitor approved for PNH and transformed the disease from frequently fatal to manageable. It’s given as an intravenous infusion every two weeks. Ravulizumab, approved in 2019, works on the same target but was engineered to last longer in the body, stretching the infusion schedule to every eight weeks after an initial loading period. Both drugs are highly effective at stopping the type of red blood cell destruction that happens inside blood vessels (intravascular hemolysis).
Crovalimab, approved in 2024, is the newest C5 inhibitor. It has a unique dosing schedule: one initial intravenous loading dose, followed by four weekly subcutaneous injections, and then maintenance injections every four weeks. The subcutaneous option makes it more practical for many patients since it can be administered at home rather than requiring an infusion center visit.
One limitation all C5 inhibitors share is that they don’t fully prevent a slower form of red blood cell destruction called extravascular hemolysis. When C5 is blocked, complement proteins earlier in the cascade can still tag red blood cells for removal by the spleen and liver. This means some patients on C5 inhibitors still have ongoing anemia despite their main symptoms improving dramatically.
Proximal Complement Inhibitors
To address the limitations of C5 blockers, newer drugs target the complement system further upstream, at the level of a protein called C3. Pegcetacoplan binds to C3 and its fragment C3b, which controls both the tagging of red blood cells for removal and the downstream destruction caused by the membrane attack complex. By acting earlier in the cascade, it addresses both types of hemolysis that PNH causes.
Pegcetacoplan is given as a subcutaneous infusion twice weekly. Patients use a small pump to infuse the medication under the skin, rotating between sites on the abdomen, thighs, hips, or upper arms. A typical infusion takes about 30 minutes when split between two sites, or about 60 minutes through a single site. For patients who experience breakthrough hemolysis (a sudden spike in red blood cell destruction), the dosing frequency can be increased to every three days or, in acute situations, given on three consecutive days.
Oral Medications
The most recent shift in PNH treatment is the arrival of pills. Iptacopan targets complement Factor B, another protein involved early in the complement cascade. It’s taken as a 200 mg capsule twice daily. For patients tired of needles and infusion schedules, this represents a major quality-of-life improvement.
Danicopan targets a different upstream protein called complement Factor D. It was initially approved as an add-on therapy for patients already on a C5 inhibitor who still have significant anemia. This combination approach is designed for people whose C5 blocker controls their intravascular hemolysis but leaves residual extravascular hemolysis unchecked.
Required Vaccinations Before Starting Treatment
All complement inhibitors carry an increased risk of meningococcal infection, a rare but potentially life-threatening bacterial disease. The complement system these drugs suppress is the same one your body uses to fight meningococcal bacteria. The CDC recommends two types of meningococcal vaccines (MenACWY and MenB) for anyone starting a complement inhibitor, ideally completed at least two weeks before the first dose. If treatment is urgent, therapy can begin before vaccination is finished, but the vaccines should be given as soon as possible.
Supportive Treatments
Complement inhibitors are the core of PNH therapy, but most patients also need supportive care to help their bodies recover from ongoing or past hemolysis. Because your bone marrow works overtime to replace destroyed red blood cells, it burns through nutrients faster than normal. Folic acid at 5 mg daily is standard to support that increased red blood cell production. Iron supplementation is given when iron stores are low, which is assessed through blood tests. Some patients, particularly those with residual anemia despite complement therapy, still need occasional red blood cell transfusions.
When Treatment Needs Adjusting
Breakthrough hemolysis, a sudden flare of red blood cell destruction, can happen even on treatment. Infections, surgeries, and other physical stressors can trigger it. When this occurs, several options exist depending on which drug you’re taking. For patients on pegcetacoplan, the infusion frequency can be increased, or a short course of a C5 inhibitor like eculizumab can be added temporarily to regain control. Transfusions may also be needed to quickly restore red blood cell counts while the medication adjustment takes effect.
Switching between drug classes is also common. A patient who starts on a C5 inhibitor but continues to have significant anemia from extravascular hemolysis might transition to pegcetacoplan or an oral Factor B inhibitor. The transition period requires careful monitoring, since there can be a temporary gap in complement coverage that risks a hemolysis flare.