BioPharma, Pharma

FDA approval of Argenx neuromuscular disease therapy is first in new drug class

Myasthenia gravis patients now have a new FDA-approved biological treatment. Argenx drug Vyvgart provides a treatment alternative for patients who have the rare autoimmune disorder and also marks the first approved product in a new class of medicines.

 

An Argenx drug developed to treat the rare neuromuscular disorder generalized myasthenia gravis is now approved by the FDA, the first therapy in a new class of medicines that takes a novel approach to treating autoimmune conditions.

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A Deep-dive Into Specialty Pharma

A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.

Myasthenia gravis develops when the body produces autoantibodies that interfere with the way nerves and muscles communicate. The disease can lead to severe attacks of weakness that cause swallowing and breathing difficulties that can become life threatening. The Argenx drug, efgartigimod, leads to a reduction in the levels of antibodies associated with myasthenia gravis. Argenx will market its new drug—the Netherlands-based company’s first product—under the name “Vyvgart.”

There are therapies available for early forms of myasthenia gravis. The class of drugs called acetylcholinesterase inhibitors stop the breakdown of a neurotransmitter key to muscle contraction, but they bring gastrointestinal side effects that include vomiting, diarrhea, and abdominal pain. This treatment is followed by corticosteroids and immunosuppressants. Steroids can lead to bone thinning and weight gain, and can contribute to diabetes and hypertension among other problems. Immunosuppressants can cause elevated liver enzymes and a greater susceptibility to infections.

Treatments for advanced cases of myasthenia gravis include intravenously administered antibodies and plasmapheresis, a procedure in which blood is removed and filtered. Both treatments introduce complication risks.

The body has built-in ways of dealing with proteins, including antibodies. It routinely removes antibodies from circulation by bringing them into cells where they are either degraded by the lysosome, which is a cellular disposal system, or they’re recycled back into circulation. A protein called neonatal Fc receptor (FcRn) is key to this recycling process. Antibodies bound to FcRn are recycled back into circulation. The ones that aren’t bound to FcRn get degraded by the cell’s disposal systems.

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Vyvgart is an antibody fragment discovered and developed from Argenx’s proprietary technology, which is based on the immune system of the llama. Argenx designed Vyvgart to bind to FcRn, which in turn prevents the recycling of the antibodies that cause myasthenia gravis. Those unbound antibodies instead go to the lysosome for degradation.

FDA approval of Vyvgart covers adults who test positive for one particular antibody that causes loss of muscle function: anti-acetylcholine receptor (AChR) antibody. Of the estimated 65,000 myasthenia gravis patients in the U.S., about 17,000 of them are positive for AChR antibody, Argenx said in an investor presentation. That’s the same group of patients addressed by Soliris, a blockbuster Alexion Pharmaceuticals treatment for several autoimmune disorders that was approved for myasthenia gravis in 2017. Alexion’s antibody drug works in a different way, binding to the complement system protein C5 in order to block the immune response that develops in myasthenia gravis.

Argenx tested Vyvgart in a placebo-controlled Phase 3 clinical trial enrolling 167 patients. The goal of the 26-week study was to assess patients according to a survey that grades myasthenia gravis symptoms. In the study, nearly 68% of patients treated with the Argenx drug responded to the treatment compared to 30% of those given a placebo. The results were also favorable to Vyvgart according to a measure of muscle weakness. Last June, results from the study were published in the journal The Lancet Neurology.

Side effects reported from the study—respiratory tract infections, headache, and urinary tract infections—were comparable across both arms. However, the FDA noted that Vyvgart also leads to a reduction in immunoglobulin G (IgG), an antibody that stops pathogens from infecting the body. Because of this reduction in IgG levels, the agency cautioned that patients face a greater risk of infection. Vyvgart’s drug label does not carry a boxed warning for dangerous side effects.

Vyvgart is the first FDA-approved drug that works by blocking FcRn, but competitors are close behind with drugs addressing the same target. Earlier this month, UCB reported data from a Phase 3 test of its subcutaneously injected FcRn-targeting antibody, rozanolixizumab. The preliminary results showed that the drug met the main goal of showing a statistically significant change in score according to the myasthenia gravis assessment. The Belgian drugmaker said regulatory submissions in the U.S., Europe, and Japan are expected in the third quarter of 2022.

Momenta Pharmaceuticals’ lead drug, nipocalimab, was the centerpiece of that company’s $6.5 billion acquisition by Johnson & Johnson last year. The intravenously infused FcRn-targeting antibody is being developed for several autoimmune disorders, including myasthenia gravis.

Speaking during a conference call Friday, Argenx Chief Operating Officer Keith Woods said the annual net price of Vyvgart for a typical patient will be $225,000. The actual price will vary depending on several factors, including a patient’s weight and the number of treatment cycles required, as well as insurance coverage, rebates, and discounts. But Woods said that Argenx has reached an agreement in principle with several national and regional payers. The agreement outlines a value-based agreement, in which reimbursement of the product is tied to the benefit that the therapy demonstrates in a patient. Woods explained that the value-based agreement will limit the exposure payers face for covering the therapy in patients who require more of the drug.

Argenx has additional plans for its lead drug. A subcutaneously injected version is currently in late-stage testing with preliminary results expected in the first half of 2022. Clinical trials are also underway evaluating efgartigimod in five other rare disorders. CEO Tim Van Hauwermeiren said that Argenx aims to expand use of its new drug to as many as 15 indications by 2025.

Photo from Argenx investor presentation