Zytux, Rituximab Biosimilar, May Be Safe, Effective for Hard-to-treat MG
These findings were reported in “Zytux in Refractory Myasthenia Gravis: A Multicenter, Open-Labeled, Clinical Trial Study of Effectiveness and Safety of a Rituximab Biosimilar,” published in the journal Frontiers in Neurology by a team of researchers in Iran.
A number of medications, including anticholinesterases, corticosteroids, and other immunosuppressants, have been found to help manage MG symptoms in those with the neuromuscular condition, which is triggered by an autoimmune response.
However, in about 10–15% of people with MG, the disease may become refractory, meaning that patients “do not entirely respond to conventional treatments or experience severe side effects related to immunosuppressive medications.”
For these individuals, monoclonal antibodies may be of benefit. One such antibody is rituximab, available under the brand name Rituxan in the U.S. and MabThera in Europe. It works by lowering the numbers of B-cells, a type of immune cells that produce antibodies and are thought to be one of the main drivers of MG and other autoimmune conditions.
“It appears that rituximab might be an appropriate alternative for patients with refractory MG with suboptimal response to the routine approaches,” the researchers wrote.
Here, investigators reported the findings of an open-label Phase 4 trial (IRCT20150303021315N18) designed to evaluate the efficacy and safety of Aryogen Pharmed’s Zytux, a product that has been designed to have properties similar to those of rituximab. A Phase 4 clinical trial studies a new treatment after it has been approved and is on the market.
The study included 34 adults (22 women and 12 men) with generalized MG of non-thymomatous origin, meaning these patients did not have a tumor, known as a thymoma, in the thymus gland. The participants were recruited at five centers across Iran. Their mean age was 48, and their symptoms first appeared at a mean age of 38.
All received 1,000 mg of Zytux per treatment cycle by into-the-vein (intravenous) infusion. The first dose was given at the beginning of the study, and the second two weeks later. The following doses were given at six-month intervals.
During the trial, patients were allowed to take their regular medications, including pyridostigmine (sold as Mestinon, among other brand names) and prednisolone. If a patient had a crisis or a worsening of symptoms, plasma exchange (plasmapheresis) or intravenous immunoglobulins (IVIG) were used for treatment.
Scores on the Myasthenia Gravis Foundation of America (MGFA) Clinical Classification, MG Composite (MGC), MG Activities of Daily Living (MG-ADL), and MG Quality of Life (MGQoL-15) scales were recorded at the beginning of the study, as well as after 12, 24, 36, and 48 weeks (almost one year).
Treatment with Zytux resulted in an improvement on the scores of the MGFA Clinical Classification over the course of the study, indicating an easing of symptoms and overall clinical improvement.
It also led to a reduction in MGC, MG-ADL, and MGQoL-15 scores, indicating less disease severity, improved ability by patients to carry out daily tasks, and better quality of life.
When researchers looked at changes in the doses of pyridostigmine and prednisolone, they found that they decreased over the course of the study, meaning that patients on Zytux required lower doses of these medications.
The results also showed the benefits were greater in those with worse disease.
“Notably, reduction of pyridostigmine dose, MG-ADL score, and MGC score were found to be more prominent in those who represent severe stages of the disease,” the researchers wrote.
In the two days following the first infusion, three patients reported a mild headache, one reported abdominal pain, and one had a fever. One other participant experienced flushing, or a redness in the face and other areas of the skin. No serious side effects were reported.
Limitations, as noted by the researchers, included the trial’s small number of participants and limited follow-up time, as well as its self-controlled open-label design.
Although the study suggested that Zytux may be effective and safe for refractory MG, “further investigations with [a] larger sample size and a more extended follow-up period are warranted to confirm this finding,” the researchers wrote.