Dupixent - withdrawal of application for variation to marketing authorisation
Application withdrawn
The application for a change to this medicine's authorisation has been withdrawn.
dupilumab
Post-authorisationHuman
Dupixent is a medicine used to treat:
- moderate to severe atopic dermatitis (also known as atopic eczema, when the skin is itchy, red and dry) in patients aged 12 years and over when topical treatments (treatments applied to the skin) are not sufficient or appropriate. Patients from 6 months up to 12 years of age can also be given the medicine if their condition is severe;
- severe asthma in patients aged 6 years and over whose asthma is not properly controlled by appropriate combination therapy (corticosteroids taken by inhalation plus another medicine used for the prevention of asthma). Dupixent is added to maintenance treatment and is only for use in patients with a type of inflammation of the airways called ‘type 2 inflammation’;
- chronic obstructive pulmonary disease (COPD), a long-term disease that causes breathing difficulties due to airway obstruction and damage to the lungs. Dupixent is used in adults who have increased levels of eosinophils (a type of white blood cell) and whose disease is not controlled well enough with a combination of a long-acting beta-2 agonist, a long-acting muscarinic agonist and an inhaled corticosteroid (other COPD medicines), or a combination of the first two if an inhaled corticosteroid is not appropriate. It is used with other medicines as maintenance (regular) treatment;
- inflammation of the nose and sinuses together with growths (polyps) obstructing the airways in the nose (chronic rhinosinusitis with nasal polyposis). It is used in adults in addition to local treatment with corticosteroids when other treatments have not worked well enough;
- moderate-to-severe prurigo nodularis (a long-term skin disease with a rash causing lumps with intense itching) in adults. It is used with or without topical (applied to the skin) corticosteroids;
- eosinophilic oesophagitis (an allergic inflammatory condition of the foodpipe) in adults and children from 1 year of age and weighing at least 15 kg, who cannot take conventional treatment or for whom it is not working.
Dupixent has been authorised in the EU since September 2017.
It contains the active substance dupilumab and is available as pre-filled pens or syringes of various strengths containing dupilumab in a solution for injection under the skin.
The company applied to extend the use of Dupixent to treat adults and adolescents aged 12 years and older with chronic spontaneous urticaria. It was to be used in patients who have disease symptoms despite treatment with H1 antihistamines and who cannot tolerate or have not adequately responded to treatment with anti-IgE therapy.
People who have the diseases for which this medicine is used produce high levels of proteins called interleukin 4 and interleukin 13 (IL-4 and IL-13). This can cause inflammation of the skin, airways and oesophagus, leading to the symptoms of these diseases. The active substance in Dupixent, dupilumab, is a monoclonal antibody (a type of protein) designed to block receptors (targets) for IL-4 and IL-13. By blocking the receptors, dupilumab prevents IL-4 and IL-13 from working and relieves disease symptoms.
In people with chronic spontaneous urticaria, Dupixent works in the same way as it does in its authorised uses.
The company presented data from a main study in 108 people with moderate to severe chronic spontaneous urticaria. All patients had persistent disease symptoms despite treatment with H1 antihistamines and could not tolerate or did not sufficiently respond to treatment with omalizumab (an anti-IgE medicine to treat urticaria). Patients were given either Dupixent or placebo (a dummy treatment) in addition to their H1 antihistamine treatment. The study measured the effectiveness of Dupixent by looking at the decrease in disease activity after 24 weeks of treatment.
The company also presented data from a supporting study in 138 people with moderate to severe chronic spontaneous urticaria who had persistent symptoms despite treatment with H1 antihistamines. This study was comparable to the main study, but patients involved had not previously received omalizumab.
The application was withdrawn after the European Medicines Agency had evaluated the information from the company and had prepared questions for the company. After the Agency had assessed the company’s responses to the questions, there were still some unresolved issues.
Based on the review of the information and the company’s response to the Agency’s questions, at the time of the withdrawal, the Agency had some concerns about the effectiveness of Dupixent in patients who had previously received an anti-IgE medicine.
In particular, the Agency noted an unpredictable clinical response in patients. In addition, some patients in the main study may have been aware of the results of an initial analysis. This could have changed the outcome of the final results, since the effect of the medicine was measured based on disease activity scores reported by patients themselves. Because the supportive study did not include patients who had previously been treated with an anti-IgE medicine, it could not provide independent evidence that Dupixent is effective in this patient group.
Therefore, the evidence presented by the company was not considered sufficiently reliable and the Agency’s provisional opinion was that the medicine could not have been authorised for the treatment of moderate to severe chronic spontaneous urticaria in patients who cannot tolerate or have not adequately responded to anti-IgE therapy.
In its letter notifying the Agency of the withdrawal of application, the company stated that they withdrew the application because they plan to submit a revised application that includes new evidence.
The company informed the Agency that there are no consequences for patients in clinical trials using Dupixent. If you or your child are in a clinical trial and need more information about your treatment, speak with your clinical trial doctor.
The withdrawal does not impact the authorised uses of this medicine to treat other diseases.