Lebrikizumab is a new potential medication that could be used to treat severe asthma. The field of asthma is seeing a new surge of biologic medications, recently approved Nucala (mepolizumab) Nucala and potentially Cinquil (reslizumab) Cinquil. Both of those medications target IL-5, a driver for eosinophils. Lebrikizumab, is a humanized monoclonal antibody that targets IL-13, which will be explained shortly.
Patients with severe refractory asthma account for 5-10% of all patients with asthma. They have poor outcomes and are not controlled with high dose inhaled corticosteroids. With the aid of biomarkers, physicians have been able to target therapy, potentially yielding better outcomes. Another example is Xolair (omalizumab), that targets IgE production against perennial allergens. Despite some patients showing improved outcomes, some patients fail to respond, revealing a need for other options. IL-13 is a central mediator in T helper cell type 2 inflammatory response and it has a prominent role in the pathology of asthma. Lebrikizumab is an anti IL-13 blocker.
In asthma, IL-13 has been linked to multiple inflammatory features. IL-13 increases the migration and survival of eosinophils, activates macrophages and increases mucus production. Both IL-4 and IL-13 increase IgE production by B cells.
IL-13 also increases Periostin production. Periostin is currently undergoing validation as a serum marker for Th2 driven inflammation in asthma.
Lebrikizumab is a human monoclonal antibody that targets IL-13. Studies have been done in uncontrolled asthmatic patients using Lebrikizumab. Patients are identified using their Periostin levels. Patients who had higher Periostin levels responded better to Lebrikizumab, their pulmonary function test results improved. Patients receiving Lebrikizumab who had elevated Periostin levels also had decreased asthma exacerbations. In another study, investigators studying Lebrikizumab have seen that patients who have elevated eosinophil counts, elevated IgE or high Periostin levels respond better than asthmatic patients who do not.
Lebrikizumab is not effective for all asthma patients. In asthma we are seeing tailored therapy. Asthma is a heterogenous disorder. There are many factors involved in worsening asthma patients. Lebrikizumab may effective for a certain subset of patients who are Th2 driven and not in other forms of asthma. It seems the patients who would benefit most from Lebrikizumab, would have high levels of Periostin, eosinophils, IgE and elevated FeNO.
Lebrikizumab appears to be safe. Side effects are similar to placebo except for musculoskeletal events. Most adverse effects of biologics are injection site reactions. Studies for efficacy are ongoing.
There are other IL-13 inhibitors being studied. Tralokiumab, Anrukinzumab and GSK679586. None of these medications have trade names yet, including Lebrikizumab. Otherwise we would have mentioned them here, because I am sure they are easier to pronounce than their generic names.
Dupilumab, which we have discussed earlier Dupilumab, blocks the alpha subunit of the IL-4 receptor and blocks both the effects of IL-4 and IL-13, this is being investigated for atopic dermatitis and asthma.
There is great interest in the potential benefits of Lebrikizumab. Genentech is currently undergoing study trials of Lebrikizumab, there are 3 trials for severe asthma, 1 for COPD and 1 for idiopathic pulmonary fibrosis.
All asthma patients should be evaluated assessed before being treated with expensive biologic medications. Lebrikizumab and other biologics should only be used after asthma education, trigger avoidance and medication have been addressed properly. Despite these measures, some patients will still not be controlled and may be a candidate for a biologic like Lebrikizumab. A large population of patients with asthma although stand to benefit from medications like Lebrikizumab. Lebrikizumab is currently undergoing trials and we will keep you informed as they progress.
Update: 2-14-17
In recent phase 3 studies, lebrikizumab failed to meet the exacerbation rate reduction or FEV1 improvement expected from prior phase 2 results. Some serious adverse events occurred as well including aplastic anemia and five related to elevated eosinophil concentrations.
The studies identified patients with either high eosinophil counts or periostin concentrations, but these markers did not identify patients well responded well to the medication. Overall, these data suggest that the underlying biology of lung function and asthma exacerbations might differ, with IL-13 not playing such a huge role in the latter. Targeting IL-13 alone might not be sufficient to provide meaningful asthma improvement.
Unfortunately these are disappointing results from the clinical trials, stay tuned for more information as we go forward.