Darzalex

Darzalex can only be obtained with a prescription and should be given by a healthcare professional in a setting where severe reactions can be quickly treated. It is given by infusion (drip) into a vein and the recommended dose is 16 mg per kilogram body weight. How often Darzalex is given depends on which other medicines are being given with it. Treatment usually starts with one dose of Darzalex a week. Before and after the infusion of Darzalex, patients are given medicines to reduce the risk of infusion-related reactions. The doctor may reduce the infusion rate or stop treatment in case of severe infusion-related reactions.

For more information about using Darzalex, see the package leaflet or contact your doctor.

The active substance in Darzalex, daratumumab, is a monoclonal antibody (a type of protein) that has been designed to recognise and attach to the protein CD38, which is found in high amounts on multiple myeloma cells. By attaching to CD38 on the multiple myeloma cells, daratumumab activates the immune system to kill the cancer cells.

Darzalex on its own was investigated in two main studies involving a total of 196 multiple myeloma patients whose disease came back after, or did not respond to, at least two previous treatments including a proteasome inhibitor and an immunomodulatory medicine. The main measure of effectiveness was the proportion of patients who responded completely or partially to treatment (as measured by the disappearance of or at least a 50% reduction in a protein found in multiple myeloma cells). Around 29% of the patients receiving Darzalex at a dose of 16 mg/kg (31 out of 106 patients) responded completely or partially to treatment in one study and 36% (15 out of 42 patients) in the second study. In these studies Darzalex was not compared with any other treatment.

Darzalex given together with dexamethasone and either lenalidomide or bortezomib was investigated in two further main studies involving patients whose multiple myeloma came back after treatment with other medicines or did not respond to the treatment. The main measure of effectiveness was how long patients lived without their disease getting worse (progression-free survival). In the first of these studies involving 569 patients, 78% of patients receiving Darzalex and dexamethasone plus lenalidomide for 18 months lived without their disease getting worse compared with 52% of those receiving dexamethasone plus lenalidomide. In the second study involving 498 patients, 61% of patients receiving Darzalex and dexamethasone plus bortezomib for 12 months lived without their disease getting worse compared with 27% of those receiving dexamethasone plus bortezomib.

Darzalex given together with dexamethasone and lenalidomide was also compared with dexamethasone plus lenalidomide in patients with newly diagnosed multiple myeloma who were not eligible for autologous stem cell transplant. The study involved 737 patients and 70% of patients receiving Darzalex and dexamethasone plus lenalidomide lived for 36 months without their disease getting worse compared with 39% of those receiving dexamethasone plus lenalidomide.

Darzalex in combination with bortezomib, melphalan and prednisone was compared with bortezomib, melphalan and prednisone in a study with 706 patients with newly diagnosed multiple myeloma who could not have autologous stem cell transplantation,. After about 28 months of starting the study, 70% (246 out of 350) of patients treated with Darzalex in combination with the other 3 medicines were alive with no worsening of their disease compared with 49% (174 out of 356) of patients treated with bortezomib, melphalan and prednisone.

The most common side effects with Darzalex (which may affect at least 1 in 5 patients) are infusion reactions, tiredness, fever, nausea (feeling sick), diarrhoea, constipation, back pain, peripheral oedema (swelling of the ankles and feet), cough, upper respiratory tract infections (such as nose and throat infections), difficulty breathing, neutropenia (low levels of neutrophils, a type of white blood cell), anaemia (low red blood cell counts), thrombocytopenia (low blood platelet counts) and peripheral sensory neuropathy (damage to the nerves in the arms and legs). Serious side effects are pneumonia (infection of the lungs), bronchitis (inflammation of the airways in the lungs), upper respiratory tract infection (nose and throat infection), pulmonary oedema (fluid build-up in the lungs), influenza (flu), fever, dehydration, diarrhoea and atrial fibrillation (irregular rapid contractions of the upper chambers of the heart). For the full list of side effects and restrictions with Darzalex, see the package leaflet.

The European Medicines Agency decided that Darzalex’s benefits are greater than its risks and it can be authorised for use in the EU. Darzalex on its own was effective at treating multiple myeloma in patients whose disease had progressed despite at least two other medicines. Darzalex used together with dexamethasone plus either lenalidomide or bortezomib has also been found effective in patients who had received other treatment for multiple myeloma. Darzalex used with lenalidomide and dexamethasone or with bortezomib, melphalan and prednisone was effective at treating patients with newly diagnosed multiple myeloma who cannot have autologous stem cell transplantation. Patients with multiple myeloma have limited treatment options and Darzalex, which works in a different way to existing treatments, represents an alternative. Darzalex’s side effects are considered acceptable and manageable.

Darzalex was originally given ‘conditional authorisation’ because there was more evidence to come about the medicine. As the company has provided the additional information necessary, the authorisation has been switched to full approval.

The company that markets Darzalex will provide educational material to all healthcare professionals expected to use the medicine, to inform them that the medicine can affect the result of a blood test (indirect Coombs test) used to determine suitability for blood transfusions. Patients who are prescribed Darzalex will be provided with a patient alert card with similar information.

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Darzalex have also been included in the summary of product characteristics and the package leaflet.

As for all medicines, data on the use of Darzalex are continuously monitored. Side effects reported with Darzalex are carefully evaluated and any necessary action taken to protect patients.

Darzalex received a conditional marketing authorisation valid throughout the EU on 20 May 2016. This was switched to a full marketing authorisation on 28 April 2017.