Ocular Myasthenia Gravis Gets Its First Targeted Biologic Candidate

Autoimmune neurology has come a long way in the last few years in terms of perspective and practice for the management of rare autoimmune conditions such as Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) and Ocular Myasthenia Gravis (oMG). For many years, the strategy for treatment of these conditions of rare autoimmune origin has involved a policy of broad and long-lasting immunosuppression or with IV treatment.

New Phase 3 Data Results

The ADAPT OCULUS trial data will be used for a sBLA for the treatment of oMG and will be submitted to the FDA later this year. The first biologic therapy to show efficacy in oMG patients, efgartigimod PH20 will provide a much-needed alternative for the treatment of oMG patients.

Why It Matters

Trial Results

The trial was designed as a Phase 3, double-blind, placebo-controlled study. The results of the trial demonstrated that patients treated with efgartigimod showed statistically significant improvements from baseline in the Myasthenia Gravis Impairment Index (MGII) Patient-Reported Outcome (PRO) ocular subscale at Week 4 compared to placebo (P=0.012). In addition to the primary endpoint, a combined assessment of patient reported outcomes and physician examination also showed statistically significant improvement in patients treated with efgartigimod compared to placebo (P=0.018).

A Precision Strike on Pathogenic Antibodies

Efgartigimod PH20 (Vyvgart), administered as a subcutaneous injection, is a human IgG1 antibody Fc fragment that specifically targets and binds to pathogenic IgG autoantibodies found in the blood of patients with certain autoimmune conditions. By binding to Fc receptors on the surface of cells that would normally recognize and remove IgG, efgartigimod PH20 SC reduces the levels of disease-causing autoantibodies in the blood that target nerve cells, without removing all IgG from the blood. Efgartigimod PH20 SC does not prevent the body from producing new antibodies. Also, efgartigimod PH20 SC does not decrease levels of albumin or cholesterol. It provides a precision strike on pathogenic antibodies while allowing an intact innate and adaptive immune system to remain functional.

• The Mechanism: Normally, a receptor called FcRn (neonatal Fc receptor) binds to IgG antibodies, preventing their destruction and recycling them back into the bloodstream.
• The Intervention: Efgartigimod is engineered with a much higher affinity for FcRn than natural IgG. It essentially “blocks” the parking spot.
• The Result: Without the ability to bind to FcRn, harmful autoantibodies are diverted to lysosomes and degraded.

The decrease in IgG levels is without a decrease in new antibody production. Importantly, efgartigimod alfa does not decrease levels of albumin or cholesterol, which are decreased by many therapies that decrease IgG levels and result in a decrease in the immune system as a whole.

Key Data at a Glance