BioPharma, Pharma

UCB Muscle Disease Drug Wins FDA Nod on Heels of Rival’s Regulatory Approval

The FDA approved UCB’s Rystiggo for treating generalized myasthenia gravis. Drugs are already available for the rare neuromuscular disorder, but Rystiggo’s approval includes treatment of a subset of patients not addressed by other products.

The available drugs for generalized myasthenia gravis address only patients whose disease exhibits a particular biological profile. The FDA has approved a new UCB drug that encompasses those covered by current treatments as well as an additional subset of patients, broadening treatment eligibility for this rare muscle-weakening disease.

With the Tuesday approval announcement, the UCB drug, rozanolixizumab, is now authorized for treating the two most common subtypes of myasthenia gravis. The Belgian drugmaker’s new product, a subcutaneous infusion, will be marketed under the brand name Rystiggo.

Myasthenia gravis is an immune disorder driven by autoantibodies that interfere with communication between nerves and muscles. In addition to skeletal muscle weakness, patients experience trouble swallowing and breathing. Those complications can be life-threatening.

UCB’s Rystiggo is intended to reduce levels of the autoantibodies driving myasthenia gravis. The disease progresses as immunoglobulin G (IgG) autoantibodies form against a receptor called AChR. These autoantibodies get recycled into circulation by binding to a receptor called FcRN. Rystiggo is an antibody designed to block IgG’s interaction with FcRN. By keeping these autoantibodies from being recirculated, they are instead broken down by a cell’s built-in protein disposal system.

FDA approval of Rystiggo is based on the results of a Phase 3 clinical trial that enrolled 200 patients. The placebo-controlled study evaluated the drug using a patient-reported scale that assesses myasthenia gravis symptoms and their impact on daily activities, such as breathing talking, swallowing, and rising from a chair. Results showed statistically significant improvement measured at day 43. The full Phase 3 results were published last month in the journal The Lancet Neurology.

“No two people living with [generalized myasthenia gravis] experience the disease in the same way, so we can’t take a ‘one size fits all’ approach to disease management,” Iris Loew-Friedrich, executive vice president and chief medical officer of UCB said in a prepared statement. “Disease management should be based on the clinical needs and preferences of the individual patient, and the aim of treatment is to help restore that patient’s ability to carry out activities of daily living. The approval of Rystiggo means doctors have an additional approved treatment option for their [generalized myasthenia gravis ] patients who have not yet found a treatment that meets their needs.”

The way UCB’s new drug works is similar to Vyvgart, an intravenously infused antibody fragment that was approved by the FDA in 2021. In fiscal 2022, Amsterdam-based Argenx reported $400.7 million in net sales for the drug. The company is now poised to offer patients a more convenient treatment option. Last week, the FDA approved an Argenx product that combines the antibody fragment in Vyvgart with an engineered enzyme that facilitates subcutaneous delivery of biologic drugs. This drug delivery technology comes from Halozyme. The newly approved Argenx product, dubbed Vyvgart Hytrulo, is administered as a subcutaneous injection that takes between 30 and 90 seconds.

Myasthenia gravis driven by AChR antibodies can also be treated by two drugs from Alexion, AstraZeneca’s rare disease subsidiary. Those blockbuster products, Soliris and Ultomiris, work by blocking a protein called C5, an approach used to treat several complement system-driven diseases. UCB can reach an additional group of patients not covered by the Alexion and Argenx drugs. FDA approval of Rystiggo includes patients positive for anti-muscle specific tyrosine kinase (MuSK) antibodies. That inclusion is based on analysis of a subgroup of MuSK-positive patients that showed numerical improvements, though the study was not powered to show statistical significance.

In a note sent to investors Tuesday, William Blair analysts Myles Minter and Matt Phipps wrote that MuSK antibody-positive patients make up a small group, about 5% of myasthenia gravis patients. However, these patients tend to have more severe and harder to treat disease compared to those who are AChR positive, representing an unmet need. While Argenx’s currently approved products do not address MuSK-positive patients, the company has reached early clinical development of an antibody that targets the MuSK antibody.

The William Blair analysts noted that the UCB drug’s label does warn of the risk of aseptic meningitis after three cases of this condition were reported in clinical testing, leading to hospitalization and discontinuation from the trial. That cautionary note does not appear on the label of Argenx’s Hytrulo. Other side effects reported on the Rystiggo label but not in at least 5% of patients treated with Hytrulo include diarrhea, fever, hypersensitivity reactions, nausea, administration site reactions, and abdominal pain.

Headache was more common in tests of the UCB drug, which the William Blair analysts note is a side effect that limits patient compliance with immunoglobulin therapy and could also be a limiting factor in earlier lines of generalized myasthenia gravis therapy. While Hytrulo showed a higher incidence of urinary tract infection, William Blair believes the Argenx drug has a superior safety and tolerability profile for earlier lines of therapy.

Public domain image by Flickr user Berkshire Community College Bioscience Image Library