July 31, 2024 – When Lisa Butler's son Stuart was 5, he got here home from school and said he had fallen on the playground and his legs hurt. The normally athletic boy began to limp and wobble, then fell down a flight of stairs.
She took Stuart to the pediatrician, who quickly realized he had a serious neurological problem and sent him to the hospital. Doctors diagnosed Stuart with Guillain-Barré syndrome, a rare neurological disorder by which an individual's immune system makes a mistake and begins to attack the peripheral nervous system (the a part of the nervous system outside the brain and spinal cord).
Guillain-Barré syndrome causes muscle weakness or paralysis, lack of reflexes and, in some cases, difficulty swallowing or respiratory. Some people die from it. Stuart was taken to intensive care and given intravenous immunoglobulins – a therapy that uses antibodies from the blood of healthy donors to spice up the patient's immune system. This was not enough and he eventually needed a second round. He made a full recovery, however it was a protracted road involving physical, occupational and aquatic therapy. He was unable to walk for about three months.
The ordeal was a “terrifying, frightening journey,” Butler said.
This is how Los Angeles Dodgers star Freddie Freeman and his wife Chelsea described their son’s diagnosis.
“Max's condition rapidly deteriorated and he suffered full body paralysis,” the couple shared on Instagram. “We are so happy to have gotten him to the hospital in time so they could strengthen his lungs. Freddie was in Houston at the time and rushed to catch the first flight home. After many tests, Max is battling a severe case of Guillain-Barré syndrome.”
“These have been the hardest, most scary days of our lives. Maximus is such a special boy and he fought SO hard.”
A brand new drug is currently being developed to treat Guillain-Barré syndrome and its manufacturer, Annexon Biosciences, hopes it can provide one other viable treatment option. Results of a central A randomized, placebo-controlled Phase III trial found that patients who received a single low-dose intravenous dose of the drug were 2.4 times more more likely to improve their health two months later than patients who received a placebo – a dummy drug with no effect.
“For stroke and other diseases, an odds ratio of over two is high,” says Henk-André Kroon, MD, head of translational medicine at Annexon Biosciences. “This is considered a positive effect and essentially shows an improvement.”
“It is the first attempt in 30 years to [Guillain-Barre]”, said Eveline Wiegers, PhD, postdoctoral fellow within the Department of Neurology at Erasmus University Medical Center in Rotterdam, Netherlands. She described the outcomes of the low dose as “very promising.”
“Because that actually means patients can return to their daily activities more often and faster,” she said.
The drug, called ANX005, is a special variety of protein that stops a harmful response within the body attributable to a molecule called C1q, which could worsen the symptoms of Guillain-Barré syndrome.
Kroon said the therapy is “very important because the classical complement system drives neuroinflammation and peripheral nerve damage in this disease and causes all the consequences that patients suffer.” The complement system is taken into account a part of an individual's natural immunity.
In other words, “they prevent irreversible nerve damage, reduce complications and improve patient outcomes,” Kroon said.
About Guillain-Barre
The exact reason behind Guillain-Barré syndrome is unknown. It generally occurs after an infection by which antibodies, typically against Campylobacter – a bacteria that causes diarrhea and may end up from eating undercooked chicken – or one other pathogen react with the peripheral nerves, Kroon said. “And that's an acute process that's completely mediated by complement,” and it quickly causes severe nerve inflammation and damage, he said.
There is a “very, very small risk” that some vaccinations could increase the danger Guillain-Barre, Wiegers said, but these studies are controversial, with some reporting that they’ll and others saying they don't. The data show The Concern about Guillain-Barré syndrome shouldn’t be a reason to not get vaccinated, she said.
Each yr, roughly two in 100,000 individuals are diagnosed with Guillain-Barré. You have a 1 in 1,000 likelihood of developing the disease over the course of your lifetime, Kroon said.
More concerning the study
The study didn’t compare “005” – because the drug's manufacturers sometimes call it for brief – with treatment with intravenous immunoglobulins or plasma exchange, one other treatment method sometimes used to treat Guillain-Barré syndrome and other autoimmune diseases, but only with supportive care.
A study compares 005 with intravenous immunoglobulin is imminent.
The results of the study showed that folks who received 30 milligrams per kilogram of body weight of the drug were 2.4 times more more likely to be in higher health after two months than individuals who received the placebo. The result is taken into account to be highly statistically significant.
Patients who received the drug also showed a major improvement in muscle strength. They were also on a ventilator for a median of 28 fewer days and were capable of walk independently for longer.
Quazi Deen Mohammad, MD, the principal investigator of the Bangladesh study and director of the National Institute of Neurosciences & Hospital in Dhaka, Bangladesh, presented data on the Peripheral Nerve Society's annual meeting in Montreal in late June.
According to at least one evaluation, the probability of complete recovery after 26 weeks was 4.14 times higher in patients treated with a dose of 30 mg/kg of the drug than in patients within the placebo group.
The study found that ANX005 was generally well tolerated. Most uncomfortable side effects were related to the infusion itself. Most reports involved mild, short-term skin rashes.
The findings on early withdrawal of the ventilator are necessary for each patients and doctors, Kroon said. With Guillain-Barré, patients lose control to the purpose where they’ll not stand and sometimes can not breathe on their very own.
The results mean “that you can interrupt the course of the disease in a large majority of patients. You can interrupt the deterioration,” Kroon said. “That is reassuring for patients. They know that something good is happening to them.”
Kroon said in an email that compared with Guillain-Barré patients in Bangladesh and the Philippines, patients within the U.S. and Europe experience symptoms somewhat earlier within the disease course and that the disease is usually milder once treatment is began..
“The Phase 3 results were confirmed in a subpopulation that corresponds to the most common patient profile in [the] USA and EU,” he said.
Annexon has not yet submitted ANX005 to the FDA for approval. First, the company needs to do more work, including more comparative studies.
One of the studies will compare Guillain-Barré patients in the Phase III trial with patients primarily in North America and Europe. Patients in higher-income countries generally have easy access to intravenous immunoglobulin and plasma exchange treatments, Wiegers said.
“I think it is a very important step to transfer these results to Europe, the US and Canada, because you want to know whether it works better or perhaps equivalent to the treatments in daily clinical practice,” said Wiegers.
“Patients have a right to choice”
The Guillain-Barré community has long needed a brand new treatment, said Butler, who’s now executive director of the GBS/CIDP Foundation International, a nonprofit that supports individuals with Guillain-Barré syndrome (GBS). “Patients have a right to selection they usually have a right to latest therapies, so it is a big deal,” she said. (CIDP stands for chronic inflammatory demyelinating polyneuropathy.)
Butler, however, does not want to criticize the intravenous immunoglobulins, which she believes saved Stuart's life. “It's an excellent treatment,” she says.
However, Kroon says intravenous immunoglobulin is only partially effective. In addition, it is generally administered over 5 days, and a potential advantage of ANX005 – If approved by the FDA, it would be a one-time infusion, he said.
Guillain-Barré is “a neurological emergency,” Kroon said. There is an acute active phase and that is what we need to focus on. “The progressive phase, by which patients present and by which they should be diagnosed and treated early, is comparatively short.”
Kroon said the company plans to apply for an FDA license in 2025. If the agency ultimately approves 005, Annexon plans to make the drug available in countries participating in the trial at a “near-cost” price, Kroon said in an email.