Pegcetacoplan, sold under the brand name Empaveli, among others, is a

medication Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...

used to treat

paroxysmal nocturnal hemoglobinuria 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 ...

and geographic atrophy of the retina. Pegcetacoplan is a

complement Complement may refer to: The arts * Complement (music), an interval that, when added to another, spans an octave ** Aggregate complementation, the separation of pitch-class collections into complementary sets * Complementary color, in the visu ...

inhibitor. The most common side effects include injection-site reactions, infections,

diarrhea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...

abdominal pain Abdominal pain, also known as a stomach ache, is a symptom associated with both non-serious and serious medical issues. Since the abdomen contains most of the body's vital organs, it can be an indicator of a wide variety of diseases. Given th ...

, respiratory tract infection, viral infection, and fatigue. Paroxysmal nocturnal hemoglobinuria is characterized by red blood cell destruction,

anemia Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availabl ...

(red blood cells unable to carry enough oxygen to tissues), blood clots, and impaired bone marrow function (not making enough blood cells). Pegcetacoplan is the first treatment for paroxysmal nocturnal hemoglobinuria that binds to and inhibits complement protein C3. Pegcetacoplan was approved for medical use in the United States in May 2021. The US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) considers it to be a

first-in-class medication A first-in-class medication is a prototype drug that uses a "new and unique mechanism of action" to treat a particular medical condition. While the Food and Drug Administration's Center for Drug Evaluation and Research tracks first-in-class medic ...

. In 2024, the American Society of Nephrology Annual Kidney Meeting, the study group who investigating pegcetacoplan in the largest multicenter double-blind VALIANT trial, showed its significant benefits in the treatment of patients with C3 glomerulopathy or primary immune complex–mediated membranoproliferative glomerulonephritis. C3 glomerulopathy leads to kidney failure in approximately 50% of patients within 5–10 years of diagnosis, and even when patients do receive a kidney transplant, approximately two thirds experience disease recurrence. Pegcetacoplan introduce a potential “kidney- and life-saving option” for patients with C3 glomerulopathy.

Medical uses

Pegcetacoplan is

indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosis ...

to treat adults with

. In February 2023, the indication was updated to include the treatment of people with geographic atrophy secondary to age-related macular degeneration. The medication is given through a subcutaneous infusion for paroxysmal nocturnal hemoglobinuria and through intravitreal injection for age-related macular degeneration.

Pharmacology

Pegcetacoplan acts as a complement inhibitor, specifically targeting complement protein C3, which plays a crucial role in the pathogenesis of paroxysmal nocturnal hemoglobinuria (PNH). In individuals with PNH, there is a heightened and uninhibited

activity, which may lead to intravascular (inside blood vessels) or extravascular (within the liver or spleen)

hemolysis Hemolysis or haemolysis (), also known by #Nomenclature, several other names, is the rupturing (lysis) of red blood cells (erythrocytes) and the release of their contents (cytoplasm) into surrounding fluid (e.g. blood plasma). Hemolysis may ...

. By binding to and inhibiting C3, pegcetacoplan helps regulate complement activation, thereby reducing red blood cell destruction, anemia, blood clot formation, and improving bone marrow function. This targeted mechanism of action makes pegcetacoplan the first-in-class medication for the treatment of PNH, offering a promising therapeutic approach to address the underlying complement dysregulation in this condition.

Pharmacokinetics

Pegcetacoplan exhibits proportional exposure with increasing doses and reaches peak concentration within 4.5–6 days after a single subcutaneous dose. Steady-state concentrations are achieved in about 4–6 weeks of treatment, with average serum trough concentrations ranging from 655 to 706 μg/mL. Pegcetacoplan is metabolized into smaller peptides and amino acids and has a median effective elimination half-life of approximately 8.0 days in patients with PNH.

Adverse effects

Meningococcal (a type of bacteria) infections can occur in people taking pegcetacoplan. Pegcetacoplan may also predispose individuals to serious infections, especially infections caused by encapsulated bacteria. These infections include but are not limited to ''

Streptococcus pneumoniae ''Streptococcus pneumoniae'', or pneumococcus, is a Gram-positive, spherical bacteria, hemolysis (microbiology), alpha-hemolytic member of the genus ''Streptococcus''. ''S. pneumoniae'' cells are usually found in pairs (diplococci) and do not f ...

'', ''

Neisseria meningitidis ''Neisseria meningitidis'', often referred to as the meningococcus, is a Gram-negative bacterium that can cause meningitis and other forms of meningococcal disease such as meningococcemia, a life-threatening sepsis. The bacterium is referred to a ...

'', and ''

Haemophilus influenzae ''Haemophilus influenzae'' (formerly called Pfeiffer's bacillus or ''Bacillus influenzae'') is a Gram-negative, Motility, non-motile, Coccobacillus, coccobacillary, facultative anaerobic organism, facultatively anaerobic, Capnophile, capnophili ...

''. Common adverse effects associated with the medication include stomach pain, vomiting, diarrhea, cold sores, common-cold like symptoms, tiredness as well as any itching, redness, or sensitivity at the injection site. Pegcetacoplan may cause fetal harm. Pegcetacoplan may also interfere with silica reagents in laboratory coagulation panels.

History

The therapeutic efficacy of subcutaneous pegcetacoplan in treating paroxysmal nocturnal hemoglobinuria (PNH) has been established through several clinical trials. Initial phase I and II trials, such as PADDOCK, PALOMINO, and PHAROAH, evaluated pegcetacoplan in PNH patients who had not received a complement inhibitor or had previously received eculizumab. These trials demonstrated that 1–2 years of pegcetacoplan treatment effectively controlled hemolysis and improved quality of life in PNH patients., Building upon these findings, the efficacy of pegcetacoplan was further assessed in phase III trials. The PRINCE trial, a 26-week study, focused on complement inhibitor-naïve patients with PNH, while the PEGASUS trial, a 48-week multinational study, included complement inhibitor-treated patients with PNH. In these trials, subcutaneous pegcetacoplan was administered at a dosage of 1080 mg twice weekly, delivered as a 20-mL subcutaneous infusion. Patients had the option to self-administer the medication or have it administered by qualified research personnel.

Society and culture

Legal status

The FDA granted the application for pegcetacoplan

orphan drug An orphan drug is a medication, pharmaceutical agent that is developed to treat certain rare medical conditions. An orphan drug would not be profitable to produce without government assistance, due to the small population of patients affected by th ...

designation. In October 2021, the

Committee for Medicinal Products for Human Use The Committee for Medicinal Products for Human Use (CHMP), formerly known as the Committee for Proprietary Medicinal Products (CPMP), is the European Medicines Agency's committee responsible for elaborating the agency's opinions on all issues regar ...

(CHMP) of the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...

(EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Aspaveli, intended for the treatment of adults with paroxysmal nocturnal hemoglobinuria. The applicant for this medicinal product is Swedish Orphan Biovitrum AB (publ). Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Pegcetacoplan was approved for the treatment of paroxysmal nocturnal haemoglobinuria in the European Union in December 2021. In June 2024, the CHMP recommended the refusal of a marketing authorization for Syfovre, a medicine intended for the treatment of geographic atrophy caused by age-related macular degeneration. The manufacturer requested a re-examination in July 2024. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. In September 2024, the CHMP continued to refuse a marketing authorization after a re-examination.

References

External links

* * * {{Authority control Complement system Immunosuppressants Ophthalmology drugs Orphan drugs