Neurological diseases such as multiple sclerosis (MS) are a very important research area for drug discovery, but under its overarching diagnosis (sometimes incorrectly) others such as neuromyelitis optica spectrum disorder (NMOSD) of rare diseases occur.
Until recently, NMOSD was considered a optic spinal form of MS. Although the clinical manifestations of NMOSD may resemble MS, NMOSD-specific serum autoantibodies (AQP4-IgG) were detected in up to 80% of patients, confirming a clinical entity distinct from MS. I’m here. Nevertheless, 41% of NMOSD patients report an initial misdiagnosis of MS, according to Horizon Therapeutics.
NMOSD is a rare, debilitating autoimmune disease caused by severe, recurrent attacks of the central nervous system (CNS) that can lead to blindness, paralysis, and death. Depending on the patient’s underlying genetic makeup, he may affect 0.4 to her 2 or 3 out of 100,000 people. Women are nine times more likely to be affected, and the median age of onset is 40 years for her.
NMOSD (also called NMO), which affects the optic nerve and spinal cord, can lead to problems such as optic neuritis and transverse myelitis, which only develops in some patients, with 41% of patients dying in about 5 years. One eye can be legally blind. After the onset of illness.
However, according to NMO UK, some people may have antibodies recognized as being associated with the disorder, such as aquaporin 4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG). However, each person with NMOSD experiences different symptoms and requires individually tailored care and support.
Changing the game with evidence and efficacy
Speaking with Kristina Patterson of Horizon Therapeutics, Pharmaforum announced UPLIZNA as a treatment for NMOSD at the 38th Congress of the European Commission for the Treatment and Research of Multiple Sclerosis (ECTRIMS) late last year. We discussed recent data. Latest discoveries.
“NMOSD is a rare and highly devastating disease. We are very excited, and we found that others were very excited as well when we presented the data showing UPLIZNA’s unique mechanistic profile at ECTRIMS.”
“In fact, one provider I spoke to, one doctor, actually called it a game changer in NMO treatment.”
In fact, one of the big hurdles is getting doctors to sign the drugs, and the response is enthusiastic. Nonetheless, the data presented by Horizon demonstrate consistent efficacy in NMOSD patients treated with UPLIZNA, regardless of specific polymorphisms or variability that may reduce response to other monoclonal antibody therapies. showed gender. Moreover, until just a few years ago, there was no approved treatment for NMOSD and no evidence-based drug.
In this trial, 89% of patients in the AQP4-IgG+ arm were relapse-free 6 months after treatment, compared to 58% of placebo patients who met their primary endpoint.
“Now we have evidence-based medicine, we have approved the medicine, and now it is about finding the right medicine for the right patient. That is the next step for NMO. From the beginning when UPLIZNA was designed, [we] Think about how a person’s underlying genetic make-up affects treatment outcomes, and basically try to treat as many patients as possible. ”
An integral role of B-cell biology
New data presented by Horizon are from two analyzes of UPLIZNA’s pivotal Phase 3 trial aimed at clarifying the relationship between peripheral B-cell subsets in the blood, AQP4IG levels, and disease attack. that’s what i got.
In NMOSD, CD19 positive-expressing B-cell lymphocytes (plasmoblasts and plasma cells) are damaged when they produce AQP4-IgG, triggering an escalating autoimmune response. Depletion of CD19+ B cells is thought to eliminate important causes of autoimmune reactions such as inflammation, lesion formation, and astrocyte damage.
UPLIZNA is a targeted CD19 B cell depletion agent specifically developed to induce broad, deep and sustained B cell depletion. It is a monoclonal antibody that specifically binds to the CD19-positive surface antigen present on pre-B and mature B-cell lymphocytes, including plasmablasts and some plasma cells. Following cell surface binding to B lymphocytes, UPLIZNA supports antibody-dependent cell lysis (ADCC) and antibody-dependent cell phagocytosis (ADCP).
“Horizon has a great interest in studying B-cell biology and the integral role of NMOSD,” Patterson explained. “Specifically, what we show here is that antibody-secreting CD19-positive B cells correlate with NMO disease activity, and that UPLIZNA only depletes or eliminates these antibody-secreting B cells. It is to reduce the levels of these diseases without causing autoantibodies that target aquaporin-4.”
“It’s really getting to the pathophysiology of the disease,” she continued. It was designed to not only be able to exert its power, but also to target the right B-cells, the CD19-positive B-cells that actually make the pathogenic antibodies that cause disease.”
Clearly thorough, precise, intensive R&D, but certainly time consuming?
“Well, science takes time,” Patterson said. “And like I said, this was conceived from the beginning. It really went into this thought process, into designing the drug, and we’ve been studying her B-cell biology ever since.” I’ve been […] Here, we take a deep dive into the different types of B cells and how they influence disease activity. ”
First-hand knowledge of doctors
This is probably why UPLIZNA is the first and only targeted B-cell depleting monotherapy approved by the EMA and FDA for this disease in adults with NMOSD and autoantibodies to aquaporin-4. Given the patient’s frightening symptoms of seizures, an important treatment to develop – Patterson is well versed in the details and is a neurologist with subspecialty training in neuroimmunology.
“Before I entered industry, maybe a year and a half ago, I was actually treating patients with NMO,” Patterson explained. “I had dozens of patients […] at my clinic. I can tell you firsthand how devastating these attacks are. Just one attack from her can completely and irreversibly change a patient’s life. Like I said, patients can be blind, they can be in wheelchairs, and they have all sorts of symptoms that affect their mobility and vision in between.
That is why UPLIZNA, which can be provided in terms of treatment, was highly evaluated by ECTRIMS.
“Being able to actually offer something to these patients, evidence-based medicine, proven effective treatments like UPLIZNA, a proven safety profile, and dosing every six months is a big deal. It was really amazing,” said Patterson. “It’s really amazing to be able to provide that to patients, and to be able to provide patients that there is a cure. A treatment in pathophysiology, a treatment that targets the underlying cause of the disease, prevents seizures, We will prevent that disorder.”
“UPLIZNA is given every six months,” she explained. “[The drug] To provide six months of protection against disease activity, and after the first two loading doses, in fact one infusion, to receive six months of protection from these devastating attacks, One 90-minute infusion every 6 months.
Future horizon focus
Given the very positive reception of the UPLIZNA data at ECTRIMS, Pharmaforum had no choice but to ask:
“There’s a lot of exciting new data we’re working with,” Patterson said. “It will also cover B-cell biology, actually all patient-centric research. there is.”
Nonetheless, Patterson was keen to share what Horizon took away from ECTRIMS itself.
“The overall message or impression Horizon had at this conference was that medical and scientific knowledge about NMO is growing rapidly. It’s a field that has made great strides, even at a conference focused on multiple sclerosis, where a great deal of research has been done on NMOSD.”
About the interviewee
Dr. Kristina Patterson joined Horizon Therapeutics in July 2021 as Medical Director, Neuroimmunology. Prior to that, he was a neurologist and his NIH-funded investigator at the University of Pennsylvania, where he worked on neuromyelitis optica spectrum disorder (NMOSD), multiple sclerosis, autoimmune encephalitis, and IgG4-mediated neuropathy. I have expertise in disease. Throughout her career, she has been passionate about optimizing therapeutic interventions for rare autoimmune diseases. Dr. Patterson graduated from Northwestern University Feinberg School of Medicine in Chicago, where she earned her medical degree and a doctorate in neuroscience. She completed a neurology residency and a neuroimmunology fellowship at the University of Pennsylvania in Philadelphia. She lives in Philadelphia with her husband and her son.