Mavrilimumab is an investigational, fully-human monoclonal antibody that targets specific molecules in the body. It is being developed as a potential treatment for various inflammatory and autoimmune conditions.
How Mavrilimumab Works
Mavrilimumab targets the granulocyte-macrophage colony-stimulating factor receptor alpha chain (GM-CSFRα). Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine that promotes the proliferation and differentiation of white blood cells like granulocytes and macrophages, enhancing their activation.
Mavrilimumab binds to GM-CSFRα, preventing GM-CSF from attaching and initiating its signaling pathways inside cells. This blockage of GM-CSF activity can reduce inflammation and immune responses that are driven by this cytokine, potentially mitigating the damage seen in inflammatory diseases.
Conditions Treated by Mavrilimumab
Mavrilimumab is being investigated for its therapeutic potential in several inflammatory and autoimmune diseases. It has shown promise in rheumatoid arthritis (RA), a chronic autoimmune disease characterized by persistent inflammation of the joints. Elevated levels of GM-CSF are found in the synovial fluid of RA patients. In Phase 2b clinical studies in Europe, mavrilimumab was administered to over 550 RA patients and achieved its predefined primary endpoints for efficacy and safety, with some patients showing sustained remission and no radiographic progression after 74 weeks.
The drug is also being evaluated for giant cell arteritis (GCA), a rare inflammatory disease affecting medium-to-large arteries. In a Phase 2 trial, mavrilimumab significantly reduced the risk of GCA flare by 62% compared to placebo over 26 weeks, with 83% of mavrilimumab recipients achieving sustained remission at week 26 compared to 50% in the placebo group. The FDA granted Orphan Drug designation to mavrilimumab for GCA in 2020.
Mavrilimumab has also been studied for its potential in treating severe COVID-19 pneumonia with systemic hyperinflammation, often referred to as a “cytokine storm.” This hyperinflammation can lead to multi-organ dysfunction. By antagonizing GM-CSF, mavrilimumab aims to reduce this excessive inflammatory response, potentially improving clinical outcomes in these patients.
Safety Profile
Mavrilimumab has been well-tolerated in clinical trials, with most reported adverse events being mild to moderate in intensity. Common side effects observed in studies have included nasopharyngitis, headache, diarrhea, and back pain.
More serious adverse events have been less frequent. For instance, in a Phase 1 study, one patient experienced moderate urticaria (hives) during an infusion, which resolved with symptomatic treatment and did not lead to study withdrawal. Long-term studies in rheumatoid arthritis patients, extending up to 74 weeks, have specifically monitored pulmonary function due to GM-CSF’s role in lung health, and no signs of pulmonary deterioration were observed. While adverse events occurred in a majority of patients in trials, serious adverse events were uncommon, and no drug-related serious adverse events were reported in a Phase 2 GCA trial.
Current Development Status
Mavrilimumab remains an investigational drug, meaning it has not yet received full regulatory approval for widespread clinical use in most indications. Kiniksa Pharmaceuticals, which licensed mavrilimumab from MedImmune, is actively pursuing its development.
Regulatory interactions with the U.S. Food and Drug Administration (FDA) have helped define the pathway for Phase 3 clinical development for rheumatoid arthritis, giant cell arteritis, and COVID-19-related acute respiratory distress syndrome. A Phase 3 clinical trial in COVID-19-related acute respiratory distress syndrome is ongoing, with data anticipated in early 2022, and this indication is considered the fastest path to potential registration. For GCA, a single, well-controlled pivotal Phase 3 trial with approximately 450 patients could be sufficient for registration, while for a broad RA population, two Phase 3 trials involving 1,000-1,500 patients with at least one year of exposure may be required.