Drug shown to be successful in treating autoimmune blood disease

Patients receiving efgartigimod, a drug being studied for the treatment of chronic primary immune thrombocytopenia (ITP), had a much greater increase in platelet counts, which are essential for clotting and stopping bleeding, in contrast to those receiving a placebo.

The Georgetown University Medical Center participated in the worldwide ADVANCE IV clinical study. Immunoglobulin G (IgG), a form of autoantibody (antibodies directed against a person’s own proteins), is present in individuals with ITP and accelerates platelet clearance from the circulation while simultaneously having the potential to decrease platelet synthesis. Particularly in individuals who have not reacted well to prior ITP medications, ITP can be exceedingly challenging to treat.

Catherine Broome, M.D., associate professor of medicine at Georgetown and lead researcher in the global ADVANCE IV project, presented the study results in a plenary session of the American Society of Hematology annual meeting in New Orleans on December 11, 2022.

“The results of the ADVANCE IV study provide an important answer regarding the potential benefits of efgartigimod as a treatment for ITP. There remains significant unmet need in treating ITP,” says Broome. “ITP is also associated with debilitating fatigue and can have significant impacts on mental health, including anxiety, fear and depression, which is why it’s been so essential to find additional therapies to treat the disease.”

According to estimates, there are around 3.3 new instances of ITP identified each year in the United States for every 100,000 persons in the general population. Females are more likely to develop ITP between puberty and 60 years of age.
The mechanism of action of efgartigimod is unique. While having no effect on crucial immune system elements including lymphocytes, IgG synthesis, or the body’s innate immune system, it reduces IgG levels.

131 individuals were enrolled in the phase III, double-blinded ADVANCE IV clinical study from North America, Europe, and Japan. For a total of 24 weeks, the subjects were randomised to receive either efgartigimod or a placebo. Prior to being randomly allocated to the experiment, every patient had low platelet counts and underwent at least one ITP therapy; two-thirds of the participants had gone through three or more ITP treatments.

The company that created the drug efgartigimod, argenx, funded the study. The medication, marketed under the trade name Vyvgart, has only been licenced for use in treating a specific kind of myasthenia gravis, a disorder characterised by impaired nerve and muscle communication brought on by autoantibodies.

In the ADVANCE IV trial, chronic ITP patients who received efgartigimod as opposed to a placebo showed a significant improvement in sustained platelet response (21.8% vs. 5%, respectively) during at least four of the last six scheduled trial visits, with about 50% of those who responded to the medication experiencing doubled platelet counts. Regardless of age, illness severity, time since diagnosis, previous ITP therapy, or usage of other drugs, response to the drug was shown in all types of patients. The drug’s negative effects that were most often reported were bruises, headaches, blood in the urine, and rash-like signs on the skin caused by bleeding. There were no documented severe treatment-related adverse effects.

“Our hope is that as more therapies are available to patients with ITP, fewer patients will experience bleeding events and fatigue, leading to an overall increase in their quality of life,” says Broome.

In this trial, the medication was given intravenously. Subcutaneous administration of the medicine is being tested concurrently to determine if it is equivalent to intravenous administration in terms of effectiveness. The second part of 2023 is when the subcutaneous trial is anticipated to provide results.

“Our next step is already underway,” says Broome, who treats patients at MedStar Georgetown University Hospital. “ADVANCE-plus is an open-label extension of this trial, that will provide data regarding long term effectiveness and safety of efgartigimod by observing participants for up to 60 weeks compared to the 24 weeks we’re reporting on now.”