Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, life-threatening disease of the blood characterized by destruction of red blood cells by the complement system, a part of the body's innate immune system. This destructive process occurs due to deficiency of the red blood cell surface protein DAF, which normally inhibits such immune reactions. Since the complement cascade attacks the red blood cells within the blood vessels of the circulatory system, the red blood cell destruction (hemolysis) is considered an intravascular hemolytic anemia. There is ongoing research into other key features of the disease, such as the high incidence of venous blood clot formation. Research suggests that PNH thrombosis is caused by both the absence of GPI-anchored complement regulatory proteins on PNH platelets and the excessive consumption of nitric oxide (NO).
Factor D is a protein which in humans is encoded by the CFD gene. Factor D is involved in the alternative complement pathway of the complement system where it cleaves factor B.
Complement decay-accelerating factor, also known as CD55 or DAF, is a protein that, in humans, is encoded by the CD55 gene.
Eculizumab, sold under the brand name Soliris among others, is a recombinant humanized monoclonal antibody used to treat paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), generalized myasthenia gravis, and neuromyelitis optica. In people with PNH, it reduces both the destruction of red blood cells and need for blood transfusion, but does not appear to affect the risk of death. Eculizumab was the first drug approved for each of its uses, and its approval was granted based on small trials. It is given by intravenous infusion.
BioCryst Pharmaceuticals, Inc. is an American pharmaceutical company headquartered in Durham, North Carolina. The company is a late stage biotech company that focuses on oral drugs for rare and serious diseases. BioCryst's antiviral drug peramivir (Rapivab) was approved by FDA in December 2014. It has also been approved in Japan, Korea, and China.
Ruxolitinib, sold under the brand name Jakafi among others, is a medication used for the treatment of intermediate or high-risk myelofibrosis, a type of myeloproliferative neoplasm that affects the bone marrow; polycythemia vera, when there has been an inadequate response to or intolerance of hydroxyurea; and steroid-refractory acute graft-versus-host disease. Ruxolitinib is a Janus kinase inhibitor. It was developed and marketed by Incyte Corp in the US under the brand name Jakafi, and by Novartis elsewhere in the world, under the brand name Jakavi.
Fostamatinib, sold under the brand names Tavalisse and Tavlesse, is a tyrosine kinase inhibitor medication for the treatment of chronic immune thrombocytopenia (ITP). The drug is administered by mouth.
Momelotinib, sold under the brand name Ojjaara, is an anticancer medication used for the treatment of myelofibrosis. It is a Janus kinase inhibitor and it is taken by mouth.
Trametinib, sold under the brand name Mekinist among others, is an anticancer medication used for the treatment of melanoma and glioma. It is a MEK inhibitor drug with anti-cancer activity. It inhibits MEK1 and MEK2. It is taken by mouth.
Binimetinib, sold under the brand name Mektovi, is an anti-cancer medication used to treat various cancers. Binimetinib is a selective inhibitor of MEK, a central kinase in the tumor-promoting MAPK pathway. Inappropriate activation of the pathway has been shown to occur in many cancers. In June 2018 it was approved by the FDA in combination with encorafenib for the treatment of patients with unresectable or metastatic BRAF V600E or V600K mutation-positive melanoma. In October 2023, it was approved by the FDA for treatment of NSCLC with a BRAF V600E mutation in combination with encorafenib. It was developed by Array Biopharma.
CD55deficiency, also called DAF deficiency or CHAPLE syndrome, is a rare genetic disorder of the immune system. CHAPLE stands for "CD55 deficiency with hyper-activation of complement, angiopathic thrombosis, and severe protein-losing enteropathy (PLE)." The disorder usually manifests in childhood and can be life-threatening. This condition was described by Özen, et al. in 2017.
Ravulizumab, sold under the brand name Ultomiris, is a humanized monoclonal antibody complement inhibitor medication designed for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome. It is designed to bind to and prevent the activation of Complement component 5 (C5).
Sutimlimab, sold under the brand name Enjaymo, is a monoclonal antibody that is used to treat adults with cold agglutinin disease (CAD). It is given by intravenous infusion. Sutimlimab prevents complement-enhanced activation of autoimmune human B cells in vitro.
Abrocitinib, sold under the brand name Cibinqo, is a medication used for the treatment of atopic dermatitis (eczema). It is a Janus kinase inhibitor and it was developed by Pfizer. It is taken by mouth.
Pegcetacoplan, sold under the brand name Empaveli, among others, is a medication used to treat paroxysmal nocturnal hemoglobinuria and geographic atrophy of the retina. Pegcetacoplan is a complement inhibitor.
Zilucoplan, sold under the brand name Zilbrysq, is a medication used for the treatment of generalized myasthenia gravis. It is a complement inhibitor that is injected subcutaneously.
Bexagliflozin, sold under the brand name Brenzavvy, is an antidiabetic medication used to improve glycemic control in adults with type 2 diabetes. It is a sodium-glucose cotransporter 2 (SGLT2) inhibitor that is taken by mouth.
The sucrose lysis test is a diagnostic laboratory test used for diagnosing paroxysmal nocturnal hemoglobinuria (PNH), as well as for hypoplastic anemias and any hemolytic anemia with an unclear cause. The test works by using sucrose, which creates a low ionic strength environment that allows complement to bind to red blood cells. In individuals with PNH, some red blood cells are especially vulnerable to lysis caused by complement. The test may also produce suspicious results in other hematologic conditions, including megaloblastic anemia and autoimmune hemolytic anemia. False-negative results can occur when complement activity is absent in the serum. A simpler alternative called the sugar water test also involves mixing blood with sugar and observing for hemolysis, using the same principle as the sucrose lysis test.
Crovalimab is an C5 inhibiting monoclonal antibody under investigation by Roche/Genentech for the treatment of paroxysmal nocturnal hemoglobinuria (PNH).
Danicopan, sold under the brand name Voydeya, is a medication used for the treatment of paroxysmal nocturnal hemoglobinuria. It is a complement inhibitor which reversibly binds to factor D to prevent alternative pathway-mediated hemolysis and deposition of complement C3 proteins on red blood cells.
