July 31, 2024 – When Lisa Butler’s son Stuart was 5 years old, he came home from school saying he fell on the playground and that his legs hurt. The typically athletic kid started limping and wobbling, then he fell down some stairs.
She took Stuart to the pediatrician, who quickly recognized he had a serious neurological problem and sent him to the hospital. Doctors diagnosed Stuart with Guillain-Barre syndrome, a rare neurological disease where a person’s immune system makes a mistake and begins to attack the peripheral nervous system (that part of the nervous system outside the brain and spinal cord).
Guillain-Barre‘ causes muscle weakness or paralysis, loss of reflexes, and, in some cases, a hard time swallowing or breathing. Some people die. Stuart went into the intensive care unit and received treatment with intravenous immunoglobulin – a therapy that uses antibodies from the blood of healthy donors to boost the patient’s immune system. It wasn’t enough, and he ultimately needed a second round. He had a complete recovery, but it was a long road filled with physical, occupational, and aqua therapy. He didn’t walk for about 3 months.
The ordeal, Butler said, was a “scary, scary journey.”
That is also the way Los Angeles Dodgers star Freddie Freeman and his wife Chelsea described their son's diagnosis.
"Max rapidly declined and went into full body paralysis," the couple shared on Instagram. "We are very fortunate to have gotten him to the hospital in time so\ they could reinforce his lungs. Freddie was in Houston at the time and rushed to the first flight back home. After many tests, Max is battling a severe case of Guillain-Barre syndrome.
"These have been the hardest and scariest days of our lives. Maximus is such a special boy and he has been fighting SO hard."
Now, a new drug is in development to treat Guillain-Barre and its maker, Annexon Biosciences, hopes it will be another viable treatment option. Results from a pivotal phase III randomized, placebo-controlled trial found that patients who took a one-time, low-dose IV of the drug were 2.4 times more likely to be in a better state of health 2 months later, compared to patients in who got the placebo – a dummy medicine that has no effect.
“In the world of stroke and other diseases, an odds ratio for greater than two is high,” said Henk-André Kroon, MD, head of translational medicine at Annexon Biosciences. “It is considered a good effect, and basically what it shows you is a shift to better.”
“It’s the first trial in 30 years that is positive in the field of [Guillain-Barre],” said Eveline Wiegers, PhD a postdoctoral researcher in the Neurology Department at Erasmus University Medical Center in Rotterdam, Netherlands. She described the results of the low dose as “very promising.”
“Because this really implies that patients are more often able to return to their daily activities and sooner,” she said.
The drug named ANX005 is a special type of protein that stops a harmful reaction in the body caused by a molecule called C1q, which could make Guillain-Barre symptoms worse.
Kroon said the therapy is “very important because classical complement drives the neuroinflammation and peripheral nerve damage in this disease and causes all the consequences that patients suffer from.” The complement system is considered part of a person’s natural immunity.
In other words: “You prevent irreversible nerve damage, you reduce complications and improve patient outcomes,” Kroon said.
About Guillain-Barre
The exact cause of Guillain-Barre is unknown. It generally occurs after an infection where antibodies typically against campylobacter – a bacteria that causes diarrhea and can result from eating undercooked chicken – or some other pathogen react with the peripheral nerves, Kroon said. “And that is an acute process, completely complement-mediated,” and it quickly causes a lot of nerve inflammation and damage, he said.
There is a “very, very slight risk” that some vaccinations might increase the risk of Guillain-Barre, Wiegers said, but these studies are controversial, with some reporting they might and others saying they don’t. Data shows that concern over Guillain-Barre syndrome should not be a reason not to get vaccinated, she said.
About two cases of Guillain-Barre are diagnosed each year out of every 100,000 people. During your lifetime, you have a 1 in 1,000 chance of developing it, Kroon said.
More About the Study
The study did not compare “005” – as its makers sometimes refer to the drug in shorthand – to treatment with intravenous immunoglobulin, or plasma exchange, another treatment sometimes used to treat Guillain-Barre and other autoimmune conditions, but only to supportive care.
A study comparing 005 to intravenous immunoglobulin is forthcoming.
Results from the study showed that people who received 30 milligrams per kilogram of weight of the drug were 2.4 times more likely to be in a better health at 2 months, compared to those who received the placebo. The finding is considered highly statistically significant.
Patients receiving the drug also showed significant improvement in muscle strength. They also spent a median of 28 fewer days on a ventilator and walked independently for longer.
Quazi Deen Mohammad, MD, the lead principal investigator of the trial in Bangladesh and director of the National Institute of Neurosciences & Hospital in Dhaka, Bangladesh, presented data at the Peripheral Nerve Society annual meeting in Montreal in late June.
In a analysis, patients treated with 30 mg/kg dose of the drug were 4.14 times more likely to be fully recovered after 26 weeks than those in the placebo group.
The study found ANX005 was generally well-tolerated. Most adverse events were related to the IV itself. Most of the reports were for mild, short-lived rashes.
The findings on getting off the ventilator early are important for both patients and doctors, Kroon said. With Guillain-Barre, patients lose control to where they are no longer able to stand and sometimes no longer able to breathe on their own.
What the results mean “is that in a large majority of patients, you can interrupt the course of disease. You interrupt the progression of getting worse.” Kroon said. “For the patient, that’s comforting. They know something is happening to them that’s good.”
Kroon said in an email that compared to Guillain-Barre patients in Bangladesh and the Philippines, those in the U.S. and Europe tend to show symptoms a little earlier in the disease process and in general tend to have milder disease when treatment is started.
"Results of the phase 3 were confirmed in a subpopulation that matches the patient profile most commonly seen in [the] US and EU," he said.
Annexon has not yet submitted ANX005 to the FDA for approval. The company still has more work to do first, including further comparison trials.
One of the trials will compare Guillain-Barre patients in the phase III study with patients mostly in North America and Europe. Patients in higher-income countries generally have ready access to IV immunoglobulin and plasma exchange treatments, Wiegers said.
“This I think is a very important step to extrapolate these results to … Europe and the U.S.A. and Canada, because you want to know … if it works better, or maybe equal to your daily clinical practice treatments,” Wiegers said.
‘Patients Deserve Choices’
The Guillain-Barre community is long overdue for a new treatment, said Butler, who is now the executive director of the GBS/CIDP Foundation International, a nonprofit that supports people affected by Guillain-Barre syndrome, or GBS. “Patients deserve choices, and they deserve new therapies, so this is huge,” she said. (CIDP stands for chronic inflammatory demyelinating polyneuropathy.)
But Butler doesn’t want to criticize intravenous immunoglobulin, which she thinks saved Stuart’s life. “It’s a good treatment,” she said.
But according to Kroon, intravenous immunoglobulin is only partially effective. Also, it is generally given over 5 days, and one potential advantage of ANX005 – should it get approved by the FDA – is that it’s a one-time infusion, he said.
Guillain-Barre is “a neurological emergency,” Kroon said. There’s an acute active phase, and that’s what you need to focus on. “The progressive phase when patients present and when they need to be diagnosed early and treated early is relatively short.”
Kroon said the company plans to seek an FDA license in 2025. If the agency ultimately approves 005, Annexon plans to make the drug available at “near cost” in countries that took part in the trial, Kroon said in an email.
