Voydeya (danicopan), marketed by Alexion Pharma, is intended for second-line use in adults with paroxysmal nocturnal hemoglobinuria (PNH) and residual hemolytic anemia. A rare disease, PNH affects around 1 in 80,000 people in France. In its opinion of October 9, 2024, the transparency commission of the High Authority for Health defined a reimbursement scope more restricted than that provided for by the marketing authorization.
Indications
Table of Contents
Voydeya, in combination with ravulizumab or eculizumab, is indicated for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH) who have residual hemolytic anemia.
Mode d’action
Danicopan inhibits complement factor D and thus specifically blocks the activation of the alternative pathway. The complement system is part of innate immunity. The alternate pathway activates spontaneously on the surface of cells, via the formation, thanks to factor D, of proteins, in particular C3 fragments. These are deposited on the surface of cells, signaling them to macrophages and other phagocytic elements. The C3 protein also allows the activation of the C5 protein and the formation of the membrane attack complex. In a healthy individual, cells are protected by regulators that prevent self-destruction. Danicopan acts on factor D, which prevents the formation of C3 and therefore reduces the lysis of erythrocytes affected by the disease, which lack protective proteins. At the same time, the inhibition of C5 (thanks to ravulizumab or eculizumab) is maintained, guaranteeing control of the consequences linked to the activation of the terminal complement pathway.
Dosage
The recommended starting dose is 150 mg taken orally 3 times daily, approximately 8 hours apart. Depending on clinical response, the dose may be increased to 200 mg 3 times daily after at least 4 weeks of treatment. Dosage adjustment is recommended in patients with severe renal insufficiency.
Contraindications
Hypersensitivity to the active substance or any of the excipients.
In patients with infection Neisseria meningitis unresolved or not having received a vaccination, unless appropriate antibiotic prophylaxis is given for up to 2 weeks after vaccination.
Pregnancy and breastfeeding
As a precaution, it is best to avoid the use of Voydeya during pregnancy and breastfeeding. Furthermore, breastfeeding should not begin less than 3 days after stopping treatment. There are no data on the effect of danicopan on human fertility.
Adverse effects
The most common are fever, headache and increased liver enzymes: increased alanine aminotransferase (Alat), abnormal liver function, increased levels of liver enzymes and transaminases.
Drug interactions
Danicopan can interact with certain transporters: it is a weak inhibitor of P-glycoprotein (P-gp) and an inhibitor of breast cancer resistance protein (BCRP). Caution is therefore recommended in the event of concomitant administration of drugs that are P-gp substrates (such as dabigatran, digoxin, fexofenadine, tacrolimus) or BCRP (for example: rosuvastatin and sulfasalazine).
Special monitoring
- Patients treated with a complement inhibitor are at increased risk of meningococcal infections, requiring up-to-date meningococcal vaccination before the first dose of danicopan. They should be monitored closely for early signs of meningococcal infection or sepsis and treated immediately if suspected.
- Patients with severe renal impairment receiving 150 mg 3 times daily and those weighing less than 60 kg require monitoring due to higher exposure.
- A liver test before treatment and regular monitoring are recommended. If clinically significant elevations of liver enzymes or symptoms occur, treatment interruption or discontinuation should be considered. Danicopan is not recommended in severe hepatic impairment.
Conservation
The shelf life is 30 months before opening the bottle, then 48 days after first opening.
Tell the patient
- Vaccination in accordance with official recommendations is recommended before starting treatment, especially in combination with ravulizumab or eculizumab.
- The tablets should be taken with a meal or snack.
- If a dose is missed, the patient should swallow it as soon as they remember, unless it is near the time of the next dose. In this case, you should not make up for the first one and continue the treatment normally with the planned dose.
The HAS opinion
Significant actual benefit “in combination with ravulizumab or eculizumab, adult patients with PNH presenting with symptomatic hemolytic anemia after treatment with a C5 inhibitor for at least 6 months”, in the same way as Aspaveli (pegcetacoplan), as well as a moderate improvement in actual benefit. The target population is estimated at 270 patients within the scope selected for reimbursement.
Deliverance
- List I, orphan drug.
- Medicine requiring special monitoring during treatment.
- Hospital prescription, reserved for doctors competent in blood diseases, specialists in hematology or internal medicine.
Technical sheet
- Voydeya 50 mg + 100 mg, film-coated tablet: 1 bottle with child safety closure of 90 tablets of 50 mg + 1 bottle with child safety closure of 90 tablets of 100 mg (CIP: 34009 302 979 0 2), €4,350.63.
- Voydeya 100 mg, film-coated tablet: 2 bottles with child safety closure of 90 tablets, i.e. 180 tablets (CIP: 34009 302 979 1 9), €5,756.55.
Prices are quoted excluding dispensing fees. Refund. at 65%.
Alexion Laboratory: 01 47 32 36 21
Paroxysmal nocturnal hemoglobinuria
By Delphine Guilloux
Also called Marchiafava-Micheli disease, paroxysmal nocturnal hemoglobinuria (PNH) is a rare condition which affects approximately 1 person in 70,000 to 80,000 inhabitants in France. PNH can occur at any age, but mainly affects young adults, with no difference between men and women.
How does it manifest?
It is a chronic disease which progresses in crises and whose triggering factors vary: an infection, a vaccine, a surgical intervention or even the administration of antibiotics. PNH can cause hemolytic anemia, thrombosis of medium and large vessels and/or moderate to severe hematopoiesis deficiency which can cause pancytopenia. The main manifestations are pallor, fatigue and shortness of breath on exertion due to anemia, dark urine at night and in the morning – even kidney failure due to hemoglobinuria – and jaundice. Thromboses can cause abdominal pain, hepatomegaly, ascites and headaches. In almost half of cases, the disease is complicated by bone marrow aplasia. The percentage of deaths within 10 years without treatment is estimated at 25%. The leading causes of death are renal failure and thromboembolic events.
What is it due to?
PNH is caused by somatic mutations in the PIG-A gene, which encodes a protein necessary for the biosynthesis of glycosylphosphatidyl-inositol (GPI) and is involved in anchoring proteins to the surface of cell membranes. The mutation, which takes place in one or more hematopoietic stem cells, results in the formation of deficient blood cells called “HPN clones”. These exhibit abnormal sensitivity to the lytic activity of complement, which is normally responsible for intravascular hemolysis as well as the activation of platelets and endothelial cells.
