Summary House dust mite extracts for allergen-specific immunotherapy (AIT) require in Germany as other common allergens (pollen from sweet grasses [except maize], birch, alder, hazel; bee and wasp venom) marketing authorisation according to the German Therapy Allergen Ordinance (“Therapieallergene-Verordnung”, [TAV]). Mite allergen extracts that have been approved and also those which are in the approval process are subject to government batch testing. Batch test passing is a prerequisite for marketability. Appropriate quality, efficacy, and safety are prerequisites for the approval of house dust mite extracts. Five HDM allergen extracts from four manufacturers are currently approved in Germany for subcutaneous or sublingual therapy; further extracts are in the approval process. The allergen strength of different products is not comparable; manufacturers use company-specific units to describe the strength. Of the three known major allergens (Group 1 allergens: Der p 1, Der f 1, Group 2 allergens: Der p 2, Der f 2 and Group 23: Der p 23, Der f 23) only Group 1 and Group 2 allergens are usually used to standardize the extracts. Group 23 allergens are localized in the outer membrane of mite faeces, and elution requires special extraction methods. To be efficacious in a single patient an allergen extracts used for AIT must contain all allergen components against which the patient is sensitised. Based on post hoc analyses of large clinical studies, it has been proven for house dust mite tablets that Der p 23 is also contained. In Germany, the Paul Ehrlich Institute is responsible for the approval of therapeutic allergens. For the marketing authorisation information on production procedures, and quality are necessary efficacy and safety (positive benefit risk ratio) of the product must be demonstrated in clinical trials according to the current state of the art.
In the majority of patients with chronic spontaneous urticaria, most currently available therapies do not result in complete symptom control. Ligelizumab is a next-generation high-affinity humanized monoclonal anti-IgE antibody. Data are limited regarding the dose-response relationship of ligelizumab and the efficacy and safety of ligelizumab as compared with omalizumab and placebo in patients who have moderate-to-severe chronic spontaneous urticaria that is inadequately controlled with H1-antihistamines at approved or increased doses, alone or in combination with H2-antihistamines or leukotriene-receptor antagonists.In a phase 2b dose-finding trial, we randomly assigned patients to receive ligelizumab at a dose of 24 mg, 72 mg, or 240 mg, omalizumab at a dose of 300 mg, or placebo, administered subcutaneously every 4 weeks for a period of 20 weeks, or a single 120-mg dose of ligelizumab. Disease symptoms of hives, itch, and angioedema were monitored by means of weekly activity scores. The main objective was to determine a dose-response relationship for the complete control of hives (indicated by a weekly hives-severity score of 0, on a scale from 0 to 21, with higher scores indicating greater severity); the primary end point of this response was assessed at week 12. Complete symptom control was indicated by a weekly urticaria activity score of 0 (on a scale from 0 to 42, with higher scores indicating greater severity). Safety was analyzed throughout the trial.A total of 382 patients underwent randomization. At week 12, a total of 30%, 51%, and 42% of the patients treated with 24 mg, 72 mg, and 240 mg, respectively, of ligelizumab had complete control of hives, as compared with 26% of the patients in the omalizumab group and no patients in the placebo group. A dose-response relationship was established. At week 12, a total of 30%, 44%, and 40% of the patients treated with 24 mg, 72 mg, and 240 mg, respectively, of ligelizumab had complete control of symptoms, as compared with 26% of the patients in the omalizumab group and no patients in the placebo group. In this small and short trial, no safety concerns regarding ligelizumab or omalizumab emerged.A higher percentage of patients had complete control of symptoms of chronic spontaneous urticaria with ligelizumab therapy of 72 mg or 240 mg than with omalizumab or placebo. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT02477332.).
