We are developing our lead product candidate, inebilizumab, as a first-line monotherapy treatment for patients with neuromyelitis optica spectrum disorder (NMOSD). Inebilizumab is a humanized monoclonal antibody designed to target and deplete CD19-expressing B cells. The byproduct of these B cells, called plasmablasts, comprise what is called the autoantibody pathway, which may in turn lead to severe autoimmune diseases such as NMSOD.
We reported results from N-MOmentum, our pivotal clinical trial with inebilizumab, and the largest study ever conducted in NMOSD. Results from the study, which were presented at the Annual Meeting of the American Academy of Neurology (AAN), demonstrated a significant reduction in risk of NMOSD attack, and an impact on measurements of worsening disability, hospitalizations and new central nervous system MRI lesions. Based on these data, we recently submitted a Biologics License Application to the U.S. FDA, which was accepted for review. If approved, we believe inebilizumab could potentially address a significant unmet need for the thousands of patients who are affected by this chronic neuroinflammatory disease.
Beyond NMOSD, we believe that inebilizumab may be effective in diseases and conditions associated with similar autoantibodies and plan to initiate trials to evaluate the potential of inebilizumab to treat myasthenia gravis, IgG4-related disease and kidney transplant desensitization.
NMOSD is a rare, severe, relapsing, neuroinflammatory autoimmune disease that attacks the optic nerve, spinal cord and brain stem. NMOSD often leads to irreversible blindness and paralysis—and in the most severe cases—this can occur with just one attack. Patients may also experience loss of sensation, bladder and bowel dysfunction, nerve pain and respiratory failure, with each subsequent attack leading to further damage and disability.
As of 2016, there were approximately 10,000 people in the U.S. suffering from NMOSD. Historically, patients have been treated with immunosuppressants, steroids and rituximab, all of which are known to cause adverse side effects and lead to treatment discontinuation. While a new therapy was recently approved for the treatment of NMOSD, it was studied in a more severe subset of patients and there remains a significant unmet need for a treatment that serves a broad patient population.
Beyond NMOSD, we believe that patients suffering with other diseases associated with CD19-expressing B cells, could potentially benefit from treatment with inebilizumab. We are planning clinical studies in the below follow-on indications:
Patients with high levels of alloantibodies waiting for a kidney transplant have a lower chance of getting a matching organ and overall worse clinical outcomes following transplant. More than 6% of the estimated 95,000 patients on the waiting list for a kidney transplant in the U.S. are considered “sensitized,” with an antibodies score of 98% to 100%. We are planning a proof of concept study to explore the potential of inebilizumab, used alone or in combination with VIB4920, to reduce levels of alloantibodies in kidney transplant candidates thereby improving transplant outcomes.
MG is a chronic, rare autoimmune neuromuscular disorder that causes abnormal weakness of skeletal muscles, which are responsible for breathing and moving parts of the body, including the arms and legs. MG, which affects about 56,000 people in the U.S., is caused by autoantibodies against the acetylcholine receptor, muscle specific kinase or other acetylcholine receptor-related proteins in the post-synaptic muscle membrane. As with NMOSD, autoantibodies secreted by plasmablasts and/or plasma cells play a key role and are thought to be directly pathogenic. Patients are currently managed with off-label immunosuppressants or steroids, or with a recently approved treatment.
This group of disorders marked by tumor-like swelling and fibrosis of affected organs, which may be caused by infiltration of CD19-expressing plasma cells that generate IgG4 antibodies. Affected organs may include the pancreas, salivary glands, retroperitoneum and kidneys. Although it is generally thought to be a rare condition, the prevalence is not well defined. A small trial of rituximab has suggested clinical benefits of B cell depletion.