information: Presentation of results at a congress
Announcement: publication of results in the Journal of Allergy and Clinical Immunology
Company: Biomay (Austria)
- fusion protein/immunotherapy product. BM32 is a grass pollen allergy vaccine based on recombinant peptide carrier technology invented in the lab of Prof. Rudolf Valenta at the Medical University of Vienna. The peptide carrier fusion proteins are constructed from the immunogenic viral coat protein PreS of the hepatitis B virus (HBV) and peptides from the IgE binding epitopes of the allergens in question; the latter have been engineered to lose their IgE binding capacity. BM32 has been designed to protect patients from the debilitating effects of grass pollen exposure and possibly provide long term cure. The product is very convenient to use for patients and doctors, as only a very small number of subcutaneous applications is needed to achieve efficient desensitization.
- The technology was developed at the Christian Doppler Laboratory for Allergy Research at MedUni Vienna, under the direction of Rudolf Valenta, in collaboration with Biomay.
Disease: grass pollen allergy
area: Allergic diseases
Country: Austria, Belgium, Denmark, Germany, The Netherlands, Slovenia
- The study is designed to evaluate the efficacy and safety of a treatment with the recombinant vaccine BM32 during two consecutive grass pollen seasons. Efficacy evaluation will be performed on the basis of allergy symptoms and use of relief medication as well as based on immunological parameters. After patient assessment during a screening season, patients will be randomized to one of two doses of BM32 or placebo. Patients will receive three injections of BM32 pre-season and one post-season boost injection to maintain optimal allergen specific IgG responses. Outcome will be measured after both seasons individually. (NCT01538979)
- In this placebo-controlled, double-blind, prospective study, 181 patients were included and initially received either of two doses of BM32 or a matching placebo. The study was coordinated by Prof. Johannes Ring (Klinik am Biederstein, Technical University of Munich, Germany); 11 trial centers in Austria, Germany, Denmark, Belgium, the Netherlands and Slovenia participated. Before the 2013 grass pollen season, patients received 3 subcutaneous injections over a period of 2 months, followed by a fall boost injection and 3 additional doses before the 2014 season. An independent data management committee (DMC) recommended that all actively treated patients should receive the lower dose (20µg of each of the four protein components) after a review of the data collected in the first treatment year. 141 patients completed all trial procedures.
- • On January 18, 2018, MedUni Vienna researchers at the Institute of Pathophysiology and Allergy Research and Biomay announced that they have now shown in a Phase II-b study with 180 patients in 11 European centres, that four injections of the synthetically manufactured vaccine BM32 in the first year and a top-up in the second year of treatment relieve the sufferers' symptoms by at least 25%. These results have been published in the Journal of Allergy and Clinical Immunology.
- The vaccine that is used and the requisite antibodies can be synthetically manufactured. This involves extracting the B-cell-reactive peptides from the allergen using a technology developed in Vienna. These peptides are modified so that they lose their bonding properties for allergen-specific IgE and serve as carrier proteins for the necessary support from T-cells.
- The researchers are assuming that the symptoms will diminish even further if the vaccination is topped up for a period of years (the available data relates to a study period of two years). Moreover, it could potentially also be used preventatively.
- A follow-on Phase III study and a simultaneous child vaccination study in compliance with all applicable guidelines is scheduled to start in 2019, to create the pre-requisites for general approval of the vaccine from 2021.
- At the same time, the investigations into the efficacy of BM32 have shown that the vaccine might also be an effective treatment for hepatitis B and could also bring relief to asthma patients. The MedUni Vienna researchers and experts at Biomay AG believe that other potential applications of BM32 are the treatment of allergies to dust mites, cats and ragweed pollen.
- • On June 2, 2015, Biomay announced that the results of a landmark phase IIb study with its 3rd generation grass pollen allergy vaccine BM32 will be reported at the EAACI Congress 2015 in Barcelona, Spain. The presentation entitled "Clinical efficacy of a recombinant B cell epitope-based grass pollen allergy vaccine – a phase IIb proof of concept study" will be given by Prof. Rudolf Valenta, a globally recognized leader in allergy research, on June 7, 2015, in the Hot Topic Session of the congress. The study, which was completed in 2014, convincingly provided clinical proof of concept for this first of kind B-cell epitope derived allergy vaccine. It was observed that the Rhinoconjunctivitis Symptom Score (RSS) year was reduced by 25% compared to the placebo (p=0.042, statistically significant) in this 181-patient trial during the peak pollen season in the second treatment. The treatment also significantly improved patients’ well-being measured by two independent methods (Visual Analogue Scale (VAS, p=0.014) and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), p<0.005). A 22% difference of a Combined Symptom and Medication Score (SMS) to placebo was also found (p=0.085). The observed clinical effects were supported by a potent and sustained induction of allergen specific IgG antibodies, which are responsible for blocking the interaction of allergens with IgE on effector cells. Unlike the established allergy vaccines derived from grass pollen extracts, BM32 did not lead to any boost of disease causing IgE production, on the contrary the seasonal boost of IgE induced by pollen exposure was significantly dampened. The treatment was safe and very well tolerated. Most side-effects were mild to moderate and resolved within a short period after drug application.
- Rainer Henning, CEO of Biomay commented: "It is a great honor for Biomay that our study has been selected by the organizers for presentation in one of the most looked-for sessions of this prestigious conference. It is in recognition of the cutting edge clinical science, which has been the result of excellent cooperation between the study investigators and the company. We look forward to discussing the data with opinion leaders in the field of allergy immunotherapy from around the globe at this event."
- A manuscript for submission to a leading peer reviewed journal in the field of allergy and immunology is also currently in preparation and will be submitted in due course.
- • On January 2, 2015, Biomay announced that the phase IIb study has been successfully completed with its 3rd generation grass pollen allergy vaccine BM32. The study was designed to show sustained alleviation of allergy symptoms over two consecutive grass pollen seasons. It was observed that the Rhinoconjunctivitis Symptom Score (RSS) during the peak pollen season in the second treatment year was reduced by 25% compared to placebo (p=0.042, statistically significant). The treatment also significantly improved patients' well being measured by two independent methods (Visual Analog Scale (VAS, p=0.014) and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ, p<0.005). A 22% difference of a Combined Symptom and Medication Score (SMS) to placebo was also found (p=0.085). The observed clinical effects were supported by a potent and sustained induction of allergen specific IgG antibodies, which are responsible for blocking the interaction of allergens with IgE on effector cells. Unlike the established allergy vaccines derived from grass pollen extracts, BM32 did not lead to any boost of disease causing IgE production. The treatment was safe and very well tolerated. Most side-effects were mild to moderate and resolved within a short period after drug application. The complete data set obtained in this trial will be presented in due course at an international conference and will be published in a leading peer reviewed journal in the field of allergy and immunology.
- • On December16, 2013, Biomay has announced that an interim analysis for futility has been successfully completed for an ongoing phase IIb study with its 3rd generation grass pollen allergy vaccine BM32. The study has enrolled 180 patients and is designed to show a treatment effect over two consecutive pollen seasons. An independent data management committee (DMC) has been appointed to analyze the data from the first treatment year with respect to the primary endpoint combined symptom and medication score (SMS) as well as the safety aspects of the treatment. The DMC has recommended continuation of the study into the next treatment year. All patients on active treatment will receive the lower of the two initial doses. The final read-out of the study is expected in the fourth quarter of 2014. Biomay will welcome a partner for phase III development, registration and marketing of BM32 as well as for the peptide carrier fusion protein platform.
- • On June 28, 2012, Biomay has announced results from a First-in-Man Phase IIa trial with its innovative allergy vaccine BM32. The vaccine significantly reduced allergy-related nasal symptoms in a study group of 70 patients suffering from grass pollen allergy. The environmental challenge study also showed that BM32 significantly reduced skin reactivity to grass pollen as demonstrated by skin prick testing. The treatment was shown to be safe and was generally well tolerated, despite the fact that a full dose of the vaccine was given from the first day of treatment. All in all, patients were given three doses of BM32 or a placebo by subcutaneous injections over a period of two months. This dosing regimen offers a dramatic improvement over conventional immunotherapy, which requires multiple injections. Biomay has already initiated a Phase IIb trial, where BM32 will be tested in 180 allergic patients under natural pollen exposure over two pollen seasons. Eleven leading allergy centers across Europe have agreed to participate in this new trial and more than 60 patients have already been enrolled. Results are expected in the fall of 2014.
- • On October 25, 2011, Biomay has announced that the company has initiated a first-in-patient phase II trial with its innovative recombinant grass pollen allergy vaccine BM32. Previously, the expected superior safety profile has been demonstrated in a phase I skin test study led by Prof. Verena Niederberger at the Vienna General Hospital. The study is conducted as a single centre trial at the Allergie-Zentrum Wien West. Primary endpoint of the study is a reduction of allergy symptoms compared to baseline, using controlled environmental exposure in the Vienna Challenge Chamber. The goal of the study is to demonstrate product efficacy by symptom reduction after just three subcutaneous injections. The study will also establish a safe and effective dosing scheme for further development of the product in larger clinical trials with pollen exposure in the patients’ natural environment. It is expected that top line data from the study will be available as early as April 2012.