An explosion of treatment options is changing the landscape of MG
by Sonya Collins
Nicole Sodder’s myasthenia gravis (MG) hit its worst point two years ago, after her second child was born.
“That’s when everything started to go downhill,” says Sodders, a 35-year-old epidemiologist who lives in Tallahassee, FL.
Pregnancy triggered MG symptoms. Her double vision, which had abated, came back. She suffered from severe morning sickness. The only cure was to eat something first thing in the morning, but she was too weak to chew or swallow. She’d choke almost every time.
After Sodders gave birth, things only got worse.
Within a few days of delivering her daughter, Sodders’ neck was so weak, she couldn’t hold her head up. She began falling, too. Eventually, she fell while trying to climb the stairs in her house, and her husband had to drag her to their bed. “That was the first time I thought, ‘Oh my gosh. I don’t want to die from this.’”
Plasmapheresis rescued Sodders from that crisis. She was symptom-free for three months. “I had forgotten what normal felt like,” she said. “Once I got a taste of that, I knew I could never accept anything less.”
“Normality” is becoming the goal and option for more and more people living with MG. As a revolution in treatment options changes the landscape, patients have more options—and more to hope for—than ever before.
There are more treatment options than ever to help patients try to achieve a virtually symptom-free life. These new medications, all approved in the last decade, are not just different brands of the same type of drug. The new generation of MG therapies has ushered in completely new ways to target the disease.
If one approach doesn’t get the desired results, it’s reasonable to try another and hope for something better.
“With the dramatic escalation in the number of new therapeutic options that are available for patients with myasthenia, minimal symptom expression—meaning that the symptoms go away or are so minimal that they are of little consequence in the person’s life—is more attainable today than it has ever been before,” says Jeffrey Rosenfeld, MD, PhD, a neurologist who treats patients with MG at Loma Linda University Health in Loma Linda, CA.
New medications, new mechanisms
Since 2017, the FDA has approved eight new medications for MG—an astonishing number, considering the last new MG medication was approved in 1955.
“The number of new treatments that have become available in just the past few years makes me believe that future therapies will likely provide even better relief and have fewer side effects,” says Kathi Timothy, the MGFA’s national community engagement and advocacy specialist, who has lived with MG since 2018.
But there’s more to be excited about than the number of new treatments, Rosenfeld says. “It’s that these drugs introduced entirely new mechanisms for addressing the disease.”
Each treatment mechanism attacks the cause of MG symptoms in different ways, which means more opportunities for patients to find a treatment that works for them.
Seven of the drugs approved in the last decade either act on complement C5 (eculizumab, ravulizumab and zilucoplan) or target neonatal Fc receptors, or FcRn (efgartigimod, rozanolixizumab, and nipocalimab). The most recently approved treatment, inebilizumab, is a CD19-targeted monoclonal antibody designed to deplete B cells.
Sodders first tried a FcRn treatment, rozanolixizumab (Rystiggo), but the effects wore off within three weeks of every dose, rather than the expected six to eight. With insurance approval, she was able to try a C5 inhibitor next. This treatment, zilucoplan (Zilbrysq), approved by the FDA in 2023, finally put Sodders’ symptoms into remission. After she started, she says, “within three days I was a new person.”
Sodders is banking on continuing to live life as that new person. “I feel like I can do anything. We’re planning a Disney cruise after my son graduates from kindergarten in May. I’m back to doing Peloton. I’m maintaining my body beyond just survival.”
A robust research pipeline
Besides drugs that act on complement C5 and FcRn, medications in the research pipeline interfere with other drivers of the disease. One experimental drug currently in development “resets the immune system to recognize itself,” says James F. Howard, Jr., MD, a professor of neurology at UNC School of Medicine in Chapel Hill, NC. “Autoimmune disease is the inability of the body to recognize itself, so it attacks it, much like it could attack an organ if you get a transplant.”
The experimental drug, currently dubbed TOL2, would repair the immune system’s tolerance for the body it inhabits. Another treatment concept in the pipeline is CAR T-cell therapy. This approach, first used to treat acute lymphoblastic B cell leukemia, involves engineering the patient’s own immune cells (T-cells) to recognize and attack harmful antigens. In the case of MG, CAR T-cell therapy would help the body attack the antibodies causing MG, such as acetylcholine receptor (AChR) antibodies, MuSK, LRP4, and potentially other unknown antibodies.
“There’s so much hope in the amount of research currently happening in the MG space,” Timothy says. “Just thinking about the MGFA’s 15th International Conference last spring fills me with optimism. Nearly 700 brilliant minds came together with the shared goal of changing the lives of those of us living with MG.”
Off-label options
Medications approved to treat other diseases, such as the cancer drug rituximab, which is approved to treat several other autoimmune disorders, may also be used off-label in people with MG who haven’t responded to any other treatments. Rituximab is what finally gave Stacy Davenport her life back.
“IVIG wasn’t for me. I’d been on Mestinon, cyclosporine, Imuran, Cellcept. Everything they’ve ever had, I’ve tried and failed them all,” says the 51-year-old nurse from Laurel, MD.
Instead she learned to live with chronic, debilitating fatigue and muscle weakness that would have her dropping surgical tools on the floor of the OR where she was a nurse. “I just had to manage it on my own,” she says. “I would just drive with one eye closed. I was really good at minimizing and faking it.” But the morning after starting rituximab, “I woke up in tears. I thought something was wrong. But what was wrong was that for the first time, I didn’t feel sick. I’d been sick for so long that feeling normal didn’t feel normal to me.”
Now she’s back to living her life in a way she hasn’t been able to do since she was diagnosed with MG in high school. “I travel. I work full time. I go out and do shenanigans on the weekends. I do everything on my own without any help. I’m okay.”
Davenport’s story may encourage others who think they’ve tried everything and that nothing will work for them.
“It wasn’t anything they did wrong that their disease is not well controlled,” Rosenfeld, the clinician from Loma Linda University, says. “It’s just that the options are greater now. So if you haven’t tried something different, now is the time.”
A faster return to “normal”
The speed at which this generation of MG treatments can work distinguishes them from past options.
Before the current targeted therapies came to the market, doctors helped patients control their symptoms through immunosuppression.
“These broad-spectrum immune suppressants take months to begin working,” Howard says. “You may not achieve the best effects for 18 to 36 months. If you have to cycle through and try another one, you’re waiting another year at least to give the drug a fair shake. That’s wasted time in someone’s life.”
While the drug’s benefits may not take hold for over a year, the increased risk for infection brought on by immunosuppressants is much swifter.
“The new targeted therapies work very rapidly,” Howard says, “and their adverse event profiles are very narrow.”
The fast action of the new targeted therapies applies to younger patients, too. Howard recounts the story of a 13-year-old patient who had been wheelchair-bound for three years, but within a week of starting on a C5 complement inhibitor, he says, “She was skipping down the hallway of the clinic.”
Changing the conversation
There is no treatment for MG that works for everyone. Researchers continue to search for biomarkers that would indicate, before starting a patient on a treatment, which one would be most likely to help them. Most of the newer medications for MG are also not approved for the roughly one in ten people who are seronegative.
“There’s still understandable caution within the seronegative community, but I’m starting to see progress in that area, too. And that’s what I choose to hold onto—hope for us all to have relief,” Timothy, who has seronegative MG, says.
It’s a valid hope to hold onto, Rosenfeld tells his patients. The sheer number of options and ever-increasing number of drug targets has, as he describes it, “changed the conversation.” Even those who are seronegative may be able to try targeted therapies off-label.
“Ten years ago, the conversation was, ‘We can restore aspects of your life.’ Now I set the bar high for my patients. We won’t get there 100% of the time, but my goal is to make the symptoms go away. Make life like it was before.”
Sonya Collins is a freelance health writer. This article was developed based on primary research, including interviews and publicly available research on MG.