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For information about active and currently recruiting MG Clinical Trials, visit the MGFA CLINICAL TRIALS webpage.

 

UCB Announces U.S. FDA Approval of ZILBRYSQ[®] (zilucoplan) for the Subcutaneous Treatment of Adults with Generalized Myasthenia Gravis

UCB Website

October 17, 2023

UCB announced that ZILBRYSQ® (zilucoplan) has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody-positive. Zilucoplan is the first once-daily subcutaneous, targeted C5 complement inhibitor for gMG and is self-administered.

 

Zilucoplan is the first once-daily subcutaneous (SC), targeted peptide inhibitor of complement component 5 (C5 inhibitor). It is the only once-daily gMG target therapy for self-administration by adult patients with anti-AChR antibody-positive gMG. Benefits of self-administered treatment can include reduced traveling time to and from hospitals, decreased interference with work obligations, and increased independence. Unlike monoclonal antibody C5 inhibitors, as a peptide, zilucoplan can be used with intravenous immunoglobulin and plasma exchange, without the need for supplemental dosing.

 

The FDA approval of zilucoplan1 is supported by safety and efficacy data from the RAISE study (NCT04115293), published in The Lancet Neurology in May 2023. The RAISE study was a multi-center, phase 3, randomized, double-blind, placebo-controlled study to assess the efficacy, safety profile, and tolerability of zilucoplan in adult patients with anti-acetylcholine receptor (AChR) antibody-positive gMG.

 

“This is an important development for the community because, with more FDA-approved treatments for generalized myasthenia gravis, physicians have additional tools to treat this disease in individualized ways that are the right fit for each individual patient,” said Samantha Masterson, President and Chief Executive Officer of the Myasthenia Gravis Foundation of America. “We are so grateful to UCB for being part of the myasthenia gravis community and their continued commitment to finding solutions for people living with this chronic, autoimmune, neuromuscular disease.”

 

With the approval of zilucoplan, alongside the company’s neonatal Fc receptor (FcRn) blocker RYSTIGGO® (rozanolixizumab-noli), which was approved earlier this year by the FDA, UCB's portfolio provides healthcare professionals the option of addressing either complement activation or pathogenic auto-antibodies for appropriate patients.

Read the official news announcement from UCB


Assessing High-dose Chemotherapy and Hematopoietic Cell Transplantation in Severe Myasthenia Gravis

Annals of Clinical and Translational Neurology

September 19, 2023

Recently published report: Remission of severe myasthenia gravis after autologous stem cell transplantation

Summary by: Dakota Campbell -Communications Program Manager- Rare Diseases Clinical Research Network, Cincinnati Children's, Cincinnati, OH 45229

 

Myasthenia gravis (MG) is a rare neuromuscular disorder caused by an autoimmune response which blocks or damages acetylcholine receptors on muscles. High-dose chemotherapy (HDIT) and autologous hematopoietic cell transplantation (HCT), also known as bone marrow transplant, are potential treatments for MG.

 

In this study, researchers investigated the safety and efficacy of HDIT and HCT in a patient with severe, treatment-resistant MG.

 

Results show that HDIT and HCT induced remission of MG. The team assessed the effect of treatment on the underlying immunopathology. Intriguingly, the acetylcholine receptor autoantibodies (AChR)—the known pathogenic mediators of the disease—did not appreciably lower after the treatment.

 

Authors state that these findings suggest a cell-based disease mechanism, which responds to high-dose therapy, may play a role in the pathology in addition to AChR autoantibodies. Further studies are needed to establish whether HDIT and HCT can be an effective therapy for severe MG.

 

You can read the entire paper in the Wiley.com library.


 

Proceedings of the 14th MGFA International Conference

RRNMF Neuromuscular Journal

August 29, 2023

 

The Proceedings of the 14th MGFA International Conference on Myasthenia Gravis and Related Disorders is now available. The proceedings were published in RRNMF Neuromuscular Journal, an open-access journal. For decades, clinicians and scientists have attended the MGFA's conference to share the latest findings in the field. It is a gathering of expert minds, both experienced researchers and up-and-coming practitioners.

 

READ the research


Telehealth in Myasthenia Gravis: What We’re Learning from a Pilot Study

Myasthenia Gravis Rare Disease Network

August 22, 2023

 

To learn more about the use of telehealth in MG, the Myasthenia Gravis Rare Disease Network (MGNet) is conducting a pilot study, “Adapting Disease Specific Outcome Measures Pilot Trial for Telehealth in Myasthenia Gravis (ADAPT-teleMG)” (clinicaltrials.gov ID NCT05917184). The team is evaluating telehealth visits and remote disease-specific assessments for patients with MG.

 

Here, lead investigator Amanda Guidon, MD, MPH, and Meridith O’Connor, MG patient and assistant vice president of patient engagement, advocacy, and policy at the Myasthenia Gravis Foundation of America (MGFA), share more about the study and its impact on the patient and research community.

 

Read the FULL ARTICLE. 


Modifying Patient T-cells Creates Novel Approach to Treating Myasthenia Gravis and other Diseases

Cartesian Website
July 1, 2023

In an effort to keep the MG Community updated on new research discoveries, we want to tell you about newly-published research in The Lancet Neurology.

Cartesian Therapeutics, an MGFA industry partner, announced the publication of positive results of the first successful clinical trial of RNA cell therapy for patients with autoimmune disease. By modifying patients’ T-cells with mRNA (a form of rCAR-T therapy), the study has created a novel approach for potentially treating myasthenia gravis (MG) and other autoimmune diseases.

The data demonstrates potent and durable clinical improvement in patients with MG, representing the first successful Phase 2 trial using RNA cell therapy.

“We are grateful to our community of MG patients and physicians for enabling clinical development of novel therapeutics such as rCAR-T,” said Samantha Masterson, President & CEO of Myasthenia Gravis Foundation of America.  “A safe, personalized therapy with durable clinical benefit would be a welcome addition to the growing toolkit of MG treatments.”

 

The results described in The Lancet Neurology paper suggest that rCAR-T may be useful in treating a variety of other autoimmune diseases and may overcome many of the risks and toxicities associated with conventional DNA-based CAR-T cells. The news release titled “Safety and Efficacy of Autologous RNA Chimeric Antigen Receptor T-cell (rCAR-T) Therapy in Myasthenia Gravis: a prospective, multicenter, open-label, non-randomized phase 1b/2a study,” is available online.

You can also download the Full Manuscript.

To learn more about Cartesian’s study with rCAR-T, or review other open and recruiting MG clinical trials that you can apply to, visit the clinical trials page.


UCB announces U.S. FDA approval of RYSTIGGO[®] (rozanolixizumab-noli) for the treatment of adults with generalized myasthenia gravis

UCB Website
June 27, 2023

More amazing and groundbreaking news from our industry partners. UCB has just announced U.S. Food and Drug Administration (FDA) approval of a new treatment called RYSTIGGO (rozanolixizumab-noli) for adults with generalized myasthenia gravis who are anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive.

Rozanolixizumab-noli is a subcutaneous infusion injection and the only FDA-approved treatment in adults for both anti-AChR AND anti-MuSK antibody-positive gMG, the two most common subtypes of gMG.

U.S. FDA approval is based on the pivotal Phase 3 MycarinG study in gMG2, a large phase 3 study which demonstrated treatment with rozanolixizumab-noli that resulted in statistically significant improvements in gMG-specific outcomes, including everyday activities such as breathing, talking, swallowing, and being able to rise from a chair.

“We want to thank UCB for their continued commitment to the MG community to bring a new FDA-approved treatment option for generalized myasthenia gravis to patients and their treating physicians,” said Samantha Masterson, President and Chief Executive Officer of the Myasthenia Gravis Foundation of America (MGFA). “People living with generalized myasthenia gravis continue to experience significant unmet medical needs, this means expanding the number of FDA-approved treatment options is particularly important to treat this chronic, autoimmune, neuromuscular disease.”

Rozanolixizumab-noli will be commercially available in the U.S. during the 3rd quarter of 2023. 

Read the official news release from UCB.


Identification of human “triple-threat” autoantibody clones in MG.

Published manuscript from Minh Pham, Kevin O’Connor, PhD and colleagues from Yale University and the University of Pennsylvania.

 

Antibodies are commonly regarded as one of our immune system’s defenses from microbes such as viruses and bacteria. However, in autoimmune diseases like myasthenia gravis (MG), some antibodies target our own tissues, thus they are termed autoantibodies. In order to better understand the causes of disease in MG, we searched for these ultra-rare autoantibodies (like a needle in a haystack) from samples donated by patients with MG.

 

Using novel technologies and strategies, we produced recombinant AChR-specific autoantibodies from MG patient samples and then investigated their biochemical properties, as well as their ability to execute pathogenic mechanisms associated with MG. We found that these autoantibodies can mediate pathology through three distinct methods: blocking binding of acetylcholine, reducing the amount of AChR, and activating complement (a part our immune systems that normally fights infections).

 

Some patients possessed “multi-potent” autoantibodies that can mediate two of these mechanisms. Surprisingly, we found several that can mediate ALL THREE of these disease mechanisms simultaneously. The lead author of our study, Minh Pham, termed these highly pathogenic and potent mediators of disease, “triple threat” autoantibodies. These “triple-threat” autoantibodies may not be efficiently targeted by some MG treatment strategies, and that developing treatment options should prioritize their elimination to better manage MG.

 

You can view abstract text, and if you are a subscriber, you can read the entire report online. If you are not a subscriber but are interested in reviewing the entire report, email Dr. Kevin O'Connor for the PDF. 


argenx Announces U.S. FDA Approval of VYVGART Hytrulo Injection for Subcutaneous Use in Generalized MG

argenx website

June 21, 2023
 

We are excited to inform you that another effective treatment for generalized myasthenia gravis has been approved by the U.S. Food & Drug Administration. argenx has announced that VYVGART® Hytrulo (efgartigimod alfa and hyaluronidase-qvfc), a subcutaneous injection for adult MG patients who are anti-acetylcholine receptor (AChR) antibody positive.

According to our industry partner argenx, VYVGART Hytrulo is a subcutaneous product combination of efgartigimod alfa, a human IgG1 antibody fragment marketed for intravenous use as VYVGART, and recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE® drug delivery technology to facilitate subcutaneous delivery of biologics. The product is to be administered subcutaneously by a healthcare professional as a single injection (1,008 mg fixed dose) over 30-90 seconds in cycles of once weekly injections for four weeks.

“The MG Community is energized and excited about another effective FDA-approved treatment available for those diagnosed with generalized MG. Thank you to our industry partner, argenx,” said Samantha Masterson, president and chief executive officer at the Myasthenia Gravis Foundation of America. “The ease and convenience of a subcutaneous injectable treatment will undoubtedly be very well-received by the patient community because the treatment process fits into the daily lives of patients around the country. Patients have an individualized approach and another important option for managing their personally unique symptoms of MG.”

VYVGART Hytrulo is expected to be available for patients in the United States in July 2023. argenx is committed to supporting access for patients to its medicines and has decided to price VYVGART Hytrulo at parity to VYVGART on a net annual revenue basis.

For more information, you can READ the news release.

Check out the official website brought to you by argenx: vyvgarthytrulo.com


Clinicoserological Insights into Patients with Immune Checkpoint Inhibitor-induced Myasthenia Gravis

Annals of Clinical and Translational Neurology

March 2023

Gianvito Masi, MD and Kevin C O’Connor, PhD
 

Cases of myasthenia gravis (MG) have been recently described as rare but life-threatening adverse events following the administration of immune checkpoint inhibitors (ICI), a novel type of cancer immunotherapy. Patients with ICI-MG often test positive for acetylcholine receptor (AChR) autoantibodies, but unlike idiopathic MG, the role of AChR autoantibodies in ICI-MG pathology is unknown. To address this, we studied a cohort of ICI-MG patients by functionally profiling their AChR autoantibodies. We found that a subset of patients may harbor AChR autoantibodies with molecular features similar to those of idiopathic MG. In other cases, however, such autoantibodies lack overt pathogenic potential, suggesting alternative factors as key mediators of disease. These findings have direct clinical implications, as they challenge the role of AChR autoantibody testing in establishing definite ICI-MG diagnoses and corroborate the need for a thorough assessment when evaluating ICI-related adverse events.

 

Read entire published paper HERE


Using the Myasthenia Gravis Patient Registry Management for Research Studies: Paul Strumph, MD

Neurology Live

February 9, 2023

Paul Strumph, MD
 

Recently, the Myasthenia Gravis Foundation of America re-launched its MGFA Global MG Patient Registry to combat these challenges for patients. In a recent interview, Paul Strumph, MD, chief medical officer at Seraxis Pharmaceuticals, and patient with MG, sat down with NeurologyLive® to discuss the attributes of the MGFA’s patient registry from a research focused perspective. He spoke on how patients can retrieve information about research studies through the registry and it how it helps researchers identify the right patients. Strumph, lead of the MGFA Global MG Patient Registry, also talked about the registry is managed by the organization with the goal of generating research.

WATCH the interview


Significance Relaunched Patient Registry/Myasthenia Gravis Research: Richard Nowak, MD, MS

Neurology Live

Feb 7, 2023

Richard Nowak, MD, MS

The MGFA partnered with Alira Health to re-launch its MGFA Global MG Patient Registry. The registry allows patients with MG to submit their health data in a secure portal, thus facilitating research to gain more knowledge on the disease, improve patient outcomes, and possibly explore more effective treatments for MG. Richard Nowak, MD, MS, assistant professor of neurology, Yale School of Medicine, sat down with NeurologyLive® in an interview to talk about the relaunch of MGFA’s patient registry. Nowak, who also serves as MGFA’s chief medical advisor, spoke about the implications and the significance of research with using the registry to recruit patients in clinical trials.

Watch the interview on Neurology Live.


Myasthenia Gravis Foundation of America (MGFA) Re-launches the MGFA Global MG Patient Registry with Partner Alira HealthSource

MGFA News Release – MGFA Website

January 25, 2023

Safe, secure registry utilizes MG patient data submissions to drive new research and discoveries for better treatments and potentially a cure for myasthenia gravis. The MGFA Global MG Patient Registry enables MG patients to submit their health and symptom data to be securely used to design and drive new research studies and clinical trials to find better treatments and potentially a cure for MG.

READ THE FULL NEWS RELEASE ONLINE

 


Precision targeting of autoantigen-specific B cells in muscle-specific tyrosine kinase myasthenia gravis with chimeric autoantibody receptor T cells

Nature Biotechnology

Senior Author: Aimee S. Payne, MD PhD

January 19, 2023

In this hot new research paper, Drs. Sangwook Oh, Aimee Payne and their colleagues detail the use of MuSK-CAART to treat MuSK MG. Muscle-specific tyrosine kinase myasthenia gravis (MuSK MG) is an autoimmune disease that causes life-threatening muscle weakness due to anti-MuSK autoantibodies, which disrupt neuromuscular junction signaling. The authors engineered T cells to create MuSK-CAART cells for precision targeting of B cells expressing anti-MuSK autoantibodies. The research shows that MuSK-CAART reduced anti-MuSK autoantibodies without decreasing healthy B cells or total immunoglobulin levels. The data contributed to an investigational new drug application and phase 1 clinical study design for MuSK-CAART for the treatment of MuSK autoantibody-positive MG.

 

Read the ENTIRE RESEARCH PAPER HERE.


2022 COVERAGE

 

FDA Accepts NDA for Myasthenia Gravis Treatment Zilucoplan

Neurology Live

November 14, 2022

According to an announcement, the FDA has accepted the new drug application (NDA) of UCB Pharma’s investigational, subcutaneously delivered agent zilucoplan for the treatment of adults with acetylcholine receptor antibody positive (AChR-Ab+) generalized myasthenia gravis (gMG). The news comes shortly after the European Medicines Agency validated the Marketing Authorization Application (MAA) of zilucoplan for the same indication.

 

Reemergence of pathogenic, autoantibody-producing B cell clones in myasthenia gravis following B cell depletion  therapy – MuSK MG Study

Myasthenia gravis (MG) is an autoantibody-mediated autoimmune disorder of the neuromuscular junction. A small subset of patients with MG, have autoantibodies targeting muscle-specifc tyrosine kinase (MuSK). MuSK MG patients respond well to CD20-mediated B cell depletion therapy (BCDT); most achieve complete stable remission. However, relapse often occurs. To further understand the immunomechanisms underlying relapse, we studied autoantibody-producing B cells over the course of BCDT. We developed an antigen to enrich for MuSK-specifc B cells, which was validated with a novel Nalm6 cell line engineered to express a human MuSK-specifc B cell receptor. Overall, this study provides both a mechanistic understanding of MuSK MG relapse and a valuable candidate biomarker for relapse prediction.

 

To read this entire study to learn more about this potential MuSK biomarker research, VISIT THE PUBLISHED RESEARCH HERE.

 

2022 MGFA Research Grant Recipients – Congratulations to our Researchers

MG experts are driving new discoveries and research every year. It is an amazing time for new research across the MG Community. Thanks to the following MG researchers for their expertise.

 

Jackie McSpadden Post-Doctoral Fellowship Award

Measuring AChR autoantibody effector functions in myasthenia gravis patients (Over 3 years, $75,000 per year)

Fatemeh Khani, MD

Yale University School of Medicine

The project investigation is focused on providing the framework for the development of MG biomarkers that can directly help patients by predicting treatment efficacy and disease progression. Dr. Khani seeks to understand immune mechanisms underlying MG that are anticipated to more precisely define this heterogeneous disease. These collective studies will provide a set of well-characterized biomarkers which will serve as tools for the community to more accurately model AChR in vitro. This project’s proposed outcome may provide a deeper understanding of the mechanisms underlying the production of autoantibodies – a highly important determination for both the patient and clinician.

 

Inaugural Nancy Law Impact Award – 2022

Preclinical models and biomarkers for predicting MuSK-CAART clinical outcomes ($300,000 over 3-year period)

Aimee Payne, MD

University of Pennsylvania

MuSK MG is caused by MuSK autoantibodies that lead to life-threatening muscle weakness, so the ideal therapy would be to eliminate autoantibody-producing B-cells while preserving healthy B-cells. CART cells in the body are currently being re-programmed to eradicate B-cell cancers, prompting researchers to explore whether this precision medicine can be used for other diseases like myasthenia gravis. The project researchers are testing a novel autoantibody receptor T-cell therapy designed to re-program MG patient T-cells to selectively kill anti-MuSK B-cells that cause MuSK MG.

 

 

 

MGFA High-Impact Pilot Project Award Recipient for 2022

Advancing patient-centered care and research for ocular myasthenia gravis: Validation of a novel patient reported outcome measure ($50,000 funded over 1-year)

Dr. Lindsey De Lott, M.D.

University of Michigan

The ocular symptoms of Myasthenia Gravis (MG) are disabling and affect quality of life - the impact of double vision and droopy eyelids can be profound. We need to fully understand the extent of how ocular symptoms impact daily function. Patient-reported outcome measures (PROMS) are valuable tools for measuring the aspects of MG, such as double vision, that matter most to patients while enhancing patient-physician communication and support. However, there are no PROMs focused on the impact of the ocular symptoms of MG or OMG nor sufficient scales to measure OMG.

 

 

Ultomiris Approved in Europe for the Treatment of Adults with Generalised Myasthenia Gravis

Ultomiris (ravulizumab) has been approved in Europe as an add-on to standard therapy for the treatment of adult patients with generalised myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody-positive. This decision marks the first and only approval for a long-acting C5 complement inhibitor for the treatment of gMG in Europe. The approval by the European Commission follows the positive opinion of the Committee for Medicinal Products for Human Use and is based on results from the CHAMPION-MG Phase III trial.

READ MORE.

 

MGFA Investigator Review on New Insights in MG Pathophysiology

The article titled “Novel pathophysiological insights in autoimmune myasthenia gravis” by Dr. Kevin O'Connor and Dr. Gianvito Masi was recently published in the journal Current Opinions in Neurology. Recent advances in the understanding of autoantibody functionalities are bringing neuroimmunologists closer to a more detailed appreciation of the mechanisms that govern MG pathology. Future investigations on the immunological heterogeneity among MG patients will be key to developing effective, individually tailored therapies.

 

You can view abstract online, and if you are a subscriber, you can read the entire report. If you are interested in reviewing the entire report, email Dr. Kevin O'Connor to receive the PDF. 

 

 

AstraZenenca/Alexion’s Ultomiris Treatment Approved in the US for Adults with Generalized Myasthenia Gravis

Ultomiris showed early effect and lasting improvement in activities of daily living and has potential to reduce treatment burden with dosing every 8 weeks

Our industry partner AstraZeneca, and its Alexion rare disease group, announced that the United States Food & Drug Administration (FDA) has officially approved the Ultomiris (ravulizumab-cwvz) treatment for adult patients with generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody-positive, which represents 80% of people living with the disease.

This FDA action marks the first and only approval for a long-acting C5 complement inhibitor for the treatment of gMG.

According to Alexion, the medication works by inhibiting the C5 protein in the terminal complement cascade, a part of the body’s immune system. When activated in an uncontrolled manner, the complement cascade over-responds, leading the body to attack its own healthy cells. Ultomiris is administered intravenously every eight weeks in adult patients, following a loading dose.

Samantha Masterson, President & Chief Executive Officer, Myasthenia Gravis Foundation of America (MGFA), said: “gMG takes a physical and emotional toll on those living with the disease. We are grateful for continued innovation and research into new treatment and dosing options to meet the needs of more patients and reduce the treatment burden. With the approval of Ultomiris, we’re excited that MG patients now have another option to consider as part of their personalised treatment strategies that may offer more convenience and improve muscle weakness.”

Marc Dunoyer, Chief Executive Officer, Alexion, said: “Since bringing forward the first complement inhibitor, we’ve continued to listen to the community and focused innovation on the needs of gMG patients. We’re proud to deliver on this commitment with today’s approval. Ultomiris, the only long-acting C5 inhibitor, will benefit a broader range of patients, including those with milder symptoms. As presented at the 2022 American Academy of Neurology Annual Meeting, Ultomiris has demonstrated clinical benefit through 60 weeks, with treatment every eight weeks, compared to Soliris every two weeks.”

Read more about this critical new treatment.

 

 

Safety and tolerability of SARS-Cov2 vaccination in patients with myasthenia gravis – Vaccination Strongly Recommended

During the COVID-19 pandemic, Myasthenia gravis (MG) patients have been identified as subjects at high-risk of developing severe COVID-19, and thus were offered vaccination with priority. The lack of direct data on the safety and tolerability of SARS-CoV-2 vaccines in MG have contributed to vaccine hesitancy. To address this issue, the safety and tolerability of SARS-CoV-2 vaccines was assessed in a large cohort of MG patients from two referral centers.

Patients with confirmed MG diagnosis, consecutively seen between October and December 2021 in two MG centers were enrolled. Demographics, clinical characteristics, and information regarding SARS-CoV-2 infection/vaccination were extracted from medical reports and/or collected throughout telephonic or in person interviews.

Our data support the safety and tolerability of mRNA-COVID-19 vaccines, which should be strongly recommended in MG patients who could be at higher risk of complications if exposed to SARS-CoV-2 infection.

Review the published research in Doc Wire News.

Read the full report in Wiley publishing and European Journal of Neurology.

 

Latest MGFA-Supported MG Research – Adverse Event Unit Project – Published in PLOS ONE

 

Dr. Michael Hehir has shared and published the first paper from the Adverse Event Unit project. This important MG Research was published in PLOS ONE. The MGFA supported and provided early funding for the project process.  

 

This paper represents the first step in important efforts to understand the adverse event burden of the treatments medical professionals use for patients with myasthenia gravis and other neurological disorders.

 

This project was initially supported by the 2016 MGFA/AAN/ABF Clinician Scientist Development Award. Through that award, Dr. Hehir was able to begin research design and implementation courses and establish the framework of the research. Additional new data analysis will be presented at upcoming conferences.

 

Since its inception in 1952, the MGFA has led the charge to support the most promising scientific endeavors—funding research, engaging young scientists and clinicians, and spearheading a comprehensive patient registry. Research has led to significant improvements in diagnostic techniques, treatments and therapies, and improved disease management. 

 

You can READ THE PUBLISHED RESEARCH in PLOS ONE using the button below.

You can also read the RESEARCH PROJECT DOCUMENT HERE.

 

 

UCB announces positive data in myasthenia gravis with zilucoplan phase 3 study results

UCB, a global biopharmaceutical company and collaboration partner with the MGFA, recently announced positive topline results from the RAISE trial evaluating its investigational treatment called zilucoplan for generalized myasthenia gravis. The results show zilucoplan was well-tolerated and no major unexpected safety findings were identified compared to earlier zilucoplan studies.

Zilucoplan is a self-administered, subcutaneous (SC) peptide inhibitor. The primary endpoint of this phase 3 study was met - a clinically meaningful and statistically significant improvement from baseline in Myasthenia Gravis-Activities of Daily Living Profile (MG-ADL) total score at Week 12. All key secondary endpoints were also met.

Please note that the safety and efficacy of zilucoplan have not been established, and it is not approved for use in any indication by any regulatory authority worldwide. But this is a very positive sign that may see a future new treatment for those diagnosed with MG.

Check out the latest news online.

 

 

argenx Announces U.S. Food and Drug Administration (FDA) Approval of VYVGART (efgartigimod alfa-fcab) in Generalized Myasthenia Gravis

argenx SE (Euronext & Nasdaq: ARGX) announced on December 17, 2021 that the U.S. Food and Drug Administration (FDA) has approved VYVGART (efgartigimod alfa-fcab) for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive. These patients represent approximately 85% of the total gMG population. With this regulatory milestone, VYVGART is the first-and-only FDA-approved neonatal Fc receptor (FcRn) blocker.

“The gMG community has long-awaited the FDA approval of VYVGART, especially for those patients who struggle with basic personal tasks such as speaking, chewing and swallowing food, brushing teeth and hair, and in some severe cases, breathing,” commented Samantha Masterson, President and Chief Executive Officer of the Myasthenia Gravis Foundation of America. “We thank argenx for its continued commitment to the gMG patient community, which led them to deliver this much-needed new treatment option with the potential to change the lives of many gMG patients.”

Read the official press release online.

argenx is committed to supporting affordable access to VYVGART. As part of this commitment, argenx is launching My VYVGART Path, a program designed to connect patients and clinicians to personalized support throughout the treatment journey. Program resources include disease and product education, access support and benefits verification, and financial assistance programs for eligible patients. Patients and healthcare providers can visit VYVGART.com for more information.

 

UCB Announces Positive Phase 3 Results for Rozanolixizumab in Generalized Myasthenia Gravis

UCB, a global biopharmaceutical company, today announced positive topline results from the Phase 3 MycarinG study1 evaluating rozanolixizumab, a subcutaneously (SC) infused monoclonal antibody targeting the neonatal Fc receptor (FcRn), versus placebo in adults with generalized myasthenia gravis (gMG). The trial met its primary endpoint, demonstrating a statistically significant and clinically meaningful change from baseline in the Myasthenia Gravis-Activities of Daily Living (MG-ADL) total score at Day 43. All secondary endpoints were also met with statistical significance.

Overall rozanolixizumab was well tolerated and no new safety signals were identified.

“For the many thousands of people living with myasthenia gravis around the world, current treatment options can be very limited,” said Samantha Masterson, Chief Executive Officer of the Myasthenia Gravis Foundation of America (MGFA). “Given that this disease causes a wide range of symptoms, some of which can require urgent intervention or hospitalization, there is a critical need for new treatment options that could address the unmet needs of patients living with myasthenia gravis.” 

READ MORE about this exciting news.

 

2021 MGFA Research Grant Recipients - Congratulations to Our Researchers

Congratulations to these deserving scientific researchers for their work to find better treatments for myasthenia. 

 

The use of Survivin as a Diagnostic Marker for Myasthenia Gravis (Committed $55,000 per year for 2 years)
Dr. Linda Kusner M.D.
The George Washington University

Nine percent of patients with myasthenia gravis (MG) cannot have a clinical diagnosis confirmed by laboratory testing for detectable antibodies, designated seronegative MG (SNMG). We have found the expression of survivin in circulating lymphocytes to correlate with the diagnosis of acetylcholine receptor antibody-positive (AChR+) MG. We have also found survivin expressed in circulating lymphocytes from patients with muscle specific kinase antibody-positive (MuSK+) and rigorously defined SNMG patients, demonstrating the potential of survivin positivity as a diagnostic marker for MG. We propose to confirm positive survivin expression in circulating lymphocytes for the context of use as a diagnostic adjunct for MG.
 

 

Indoleamine-2, 3-dioxygenase 2 (IOD2) as a Novel Therapeutic Target for the Treatment of Myasthenia Gravis (Committed $55,000 per year for 2 years)
Dr. Laura Mandik-Nayak M.D.
Lankenau Institute for Medical Research

Myasthenia gravis (MG) is widely recognized as a B cell-mediated disease, with autoantibody production critical to its development and progression. While there has been intense interest in the development of therapies that deplete B cells or prevent B cell activation, these therapies are not effective in all patients and there is a continued need for new therapies. In this proposal, we will use a preclinical model of MG, together with a novel IDO2-targeting approach, to explore IDO2 inhibition as a novel therapeutic strategy to treat MG. In the short term, our studies will provide an initial step in the preclinical evaluation of IDO2 as a therapeutic target in the treatment of MG. If successful, the potential longterm impact of this project would move the concept of IDO2-directed therapy into development as a novel strategy to treat human MG.

 

 

MGFA & American Brain Foundation Partnering on New Clinical Research Award for MG

July 1, 2021

MGFA is partnering with the American Brain Foundation on a clinical research award for myasthenia gravis. The application opens on July 1 and runs through October 1.

 

This award aims to recognize the importance of good clinical research and to encourage young investigators in clinical studies related to myasthenia gravis. It will consist of a commitment of $75,000 per year for three years, plus a $5,000 per year stipend to support education and research-related costs for a total of $240,000. Supplementation of the award with other grants is permissible, but to be eligible to apply for this award, the other grant source(s) cannot exceed $80,000 annually. Please only submit one application - applicants are not allowed to submit applications for more than one award. Your application will also be considered for all relevant clinician-scientist development awards.

IMPORTANT DATES

October 1, 2021: Application deadline: Note that this is the deadline for all documents, including those from the mentor and chair. Applications will be declined if this information is not submitted by October 1.

January 2022: Notification of recipients

July 1, 2022: Funding begins

COVID-19 Associated Risks and Effects in Myasthenia Gravis (CARE-MG)

CARE-MG, a physician-reported registry, is a joint effort of the International MG/COVID-19 Working Group and neurologists from across the globe to capture outcomes of people with MG who have developed COVID-19 infections formally launched on 09 April 2020.

 

Robust international participation and collaboration is critical to our collective success in answering fundamental questions: Do MG patients face special risks? Do baseline therapies impact risk? Together, the two groups along with several independent experts have designed and launched this international registry. Click here to learn about the current CARE-MG Research Policy.

 

 We hope to capture outcomes in all types of myasthenia gravis (AChR, MuSK, LRP4, Seronegative) irrespective of current treatment status who have confirmed of suspected COVID-19 infection.

 Definitions:

  • Laboratory Confirmed COVID-19 - Positive viral RNA tests or positive serology for SARS-CoV-2
  • Suspected COVID-19 but not confirmed - Fever with Dry cough, +/- anorexia, myalgias, dyspnea, anosmia/ageusia, potential exposure, Chest imaging suggestive of COVID
  • Myasthenia Gravis: As defined by treating physician based on antibody status and if seronegative (based on standard testing such as repetitive testing, single fiber EMG, response to acetylcholine esterase inhibitors)

Learn More about CARE-MG.

See the Current CARE-MG Policy.

 

NeuroSeries Online Event Focused on MG Diagnostics and Treatments Webinar 

Current management options for generalized myasthenia gravis (gMG) often leave patients with uncontrolled symptoms and frequent myasthenic crises. Recent improvements in the understanding of the complex pathophysiology of gMG, including the pivotal role of IgG autoantibodies, have led to new antibody tests to improve diagnoses. In addition, targeted treatment options may help address the need for a more rapid onset of effect while improving efficacy.

 

    

 

Join moderator James Howard Jr., MD and esteemed speaker Nicholas Silvestri, MD, FAAN as they discuss emerging biomarkers and autoantibody tests to improve diagnosis, provide patient-centered management, and enhance patient- and physician-reported outcomes. Webinar replay from Tuesday, March 9, 2021.

 

This NeuroSeries event is provided by PlatformQ Health Education, LLC working in collaboration with the Myasthenia Gravis Foundation of America (MGFA), National Organization for Rare Disorders (NORD), and the Muscular Dystrophy Association (MDA).

 

MGFA Partner argenx Offers Two Year MG Study called MyRealWorld MG 

MyRealWorld MG is an international two-year study assessing the impact of Myasthenia Gravis on patients’ lives. Be part of this meaningful argenx-sponsored research study to better understand the lives of people living with MG. Working with patient organizations from 9 countries (US, Japan, Germany, UK, France, Italy, Spain, Canada, Belgium), biotechnology company argenx sponsors this innovative study and is inviting MG patients from around the world to participate and share information. You can download and use the MyRealWorld mobile app to enter data. READ MORE about this study HERE.

 

 

MGFA Proudly Announces its Research Pilot Grant Recipients for 2020:

Congratulations to these deserving scientific researchers for their work to find better treatments for myasthenia. 

 

Identification of biomarkers that leverage mechanisms of autoantibody pathology in AChR MG ($55,000 - One Year Award)

Dr. Kevin O’Connor

Yale University

MG is characterized by the presence of acetylcholine receptor antibodies in the blood, which cause the disease by different mechanisms which are not fully understood. We are developing a group of assays that classify and quantify these antibody types to predict treatment response, monitor disease progression, and enable personalized therapeutic decisions that avoid severe side effects.

 

Measuring adverse event burden in myasthenia gravis: Validation on adverse event unit ($55,000 - One Year Award)

Dr. Michael Hehir

University of Vermont

There is increasing emphasis on long term side effect burdens for patients with MG as we attempt to understand differences between treatments. Understanding the side effect burden is paramount when designing unique treatment strategies. We have created a patient and physician consensus unit (akin to currency such as the US Dollar) called the Adverse Event Unit (AEU) to better measure this burden. The goal of the project is to evaluate the validity, utility, and feasibility of using the AEU as a measure of MG treatment burden.

 

Seronegative Grants

Defining the clinical phenotype and immunopathology of seronegative MG ($150,000 - 2 Year Award)

Dr. Jeffrey Guptill - Duke University

Dr. Kevin O’Connor – Yale University

Seronegative MG (SNMG) is a disease subset of MG defined by the absence of detectable autoantibodies that are otherwise present in a majority of patients. Little is known about SNMG and it has not been well-studied. Two major goals of this project include: 1) to better understand the characteristics of SNMG patients, and 2) to better understand the abnormal immune system functions that contribute to this disease subset. This work will define the features that will lead to better treatment guidance in the future.

 

MGFA Transformative Grant Generates New Paper on Potential MG Biomarkers

Circulating Th1/17 cells a biomarker of disease severity and target for early intervention for MG patients.
 

Dr. Jeff Guptill and research staff at the Duke Early Phase Clinical Research Unit at Duke University Medical Center has submitted another new paper that has been accepted by the Journal of Neuroimmunology. The research was the result of a transformative grant provided by the Myasthenia Gravis Foundation of America.
 

This study focuses on a group of patients with myasthenia gravis (MG) who have anti‐muscle‐specific kinase antibodies (MuSK-MG). Patients with MuSK-MG tend to respond well to therapies that lower anti-MuSK antibodies. Follicular helper T (Tfh) cells are a type of immune cell (a subset of T-cells) that help another type of immune cell, called B cells, produce antibodies.
 

Tfh cells are not well-studied in MuSK-MG patients. In this study, we found that T cells in MuSK-MG promote inflammation. In addition, a subset of Tfh cells, called Tfh17 cells, are higher among patients with MuSK-MG than healthy people without MuSK-MG. These Tfh17 cells are in part responsible for the inflammatory response in MuSK-MG and may help B cells produce more antibodies.
 

In summary, these results support a role for Tfh cell dysfunction in MuSK-MG. Highly specific treatment strategies to rebalance Tfh cells are a potential target for treating patients with MuSK-MG in the future.


Click here to read the article or click here to read the full report.

 

Momenta Pharmaceuticals Announces New Results for nipocalimab in MG Patients

Momenta announced positive topline results from their interim analysis of the Vivacity-MG study investigating nipocalimab in patients with #MyastheniaGravis (MG). Read more about the results here.

 

Key highlights from the presentation we made this morning:

  • 52% of patients who received nipocalimab had rapid, significant and durable reductions in MG-ADL scores (at least a 2-point reduction from baseline for at least 4 consecutive weeks) across all doses, versus 15% of placebo treated patients.
  • A statistically significant relationship was observed between autoantibody (IgG) reduction and clinical benefit for patients taking nipocalimab (p<0.0001).
  • Patients across all four nipocalimab dosing arms showed rapid reductions in MG-ADL scores, with clinically meaningful changes in scores within two weeks. Anti-MuSK patients were also included in the study and had similar responses.
  • Nipocalimab was well tolerated, safe and efficacious in gMG patients. There were no severe or serious nipocalimab-related adverse events and most adverse events were characterized as mild.
  • The study findings support continued clinical development in gMG and subcutaneous formulation dose selection.

 

 

Guidance for the management of Myasthenia Gravis (MG) and Lambert-Eaton Myasthenic Syndrome (LEMS) during the COVID-19 pandemic

March 23, 2020 
International MG/COVID Working Group* 

International MG/COVID-19 Working Group1 SaijuJacoba2 SrikanthMuppidib2 AmandaGuidonc JeffreyGuptilld MichaelHehire James F.HowardJrf IsabelIllag RenatoMantegazzah HiroyukiMuraii KimiakiUtsugisawaj JohnVissingk HeinzWiendll Richard J.Nowakm2
Corona Virus Disease 2019 (COVID-19) is a new illness caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Symptoms are variable but typically include fever, cough, respiratory symptoms, diarrhea, reduction of smell and taste sensation. Severity ranges from mild to severe and the virus may lead to pneumonia, acute respiratory distress syndrome and death, in some patients. Nearly every country in the world has been affected by this virus and is currently defined as a pandemic, by the World Health Organization. There are no known proven therapies for treating this virus and no vaccine to prevent the infection at this time. 

 

The full guidance is available here

 

Clinical Effects of the Self-administered Subcutaneous Complement Inhibitor Zilucoplan in Patients With Moderate to Severe Generalized Myasthenia GravisResults of a Phase 2 Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Trial

Many patients with generalized myasthenia gravis (gMG) have substantial clinical disability, persistent disease burden, and adverse effects attributable to chronic immunosuppression. Therefore, there is a significant need for targeted, well-tolerated therapies with the potential to improve disease control and enhance quality of life.

 

The findings of the above-mentioned study, published by JAMA Neurology, support a potential therapeutic role for zilucoplan in generalized myasthenia gravis and further evaluation in a phase 3 study. 

 

University of California, San Francisco, Launches First Consortium on Pediatric MG in Partnership with MGFA and MDA

For families with children that have myasthenia gravis, we have some exciting news to share. Thanks to a generous gift from an anonymous donor to the University of California, San Francisco, the first clinical Pediatric Myasthenia Gravis Consortium is now a reality.  MGFA was honored to provide a grant to underwrite the costs for the September inaugural meeting of this exciting new project, and to participate on the advisory committee for the Consortium.

 

Response to Treatment in Pediatric Ocular MG 

In children, myasthenia gravis (MG) almost always appears in one of two forms: ocular myasthenia gravis (OMG), where weakness is evident only in the eyelids and surrounding tissue, whereas in generalized myasthenia gravis (GMG), various tissues throughout the body are affected. This study, published in Muscle & Nerve,  examines how these two disease types tend to differ from a clinical perspective, as well as patient response to treatment. 

 

National Institutes of Health (NIH) Awarded a Research Team at the George Washington University (GW) $7.8 million to Establish a Rare Disease Network for Myasthenia Gravis

The National Institutes of Health (NIH) has awarded a research team at the George Washington University (GW) $7.8 million to establish a rare disease network for myasthenia gravis. The network, which will be part of 25 established NIH Rare Diseases Clinical Research Networks, will include basic and clinical investigators, patient advocacy groups and biotechnology and pharmaceutical companies working together to enhance therapeutic development for this rare disease.  The team is led by former and current MGFA Medical and Scientific Advisory (MSAB) Chairs, Henry Kaminski, MD and Linda Kusner, PhD, and the steering committee members are all leaders of the MGFA MSAB as well. 

 

The grant will fund research into the underlying pathophysiology of the disease, provide fellowships in MG for young investigators, and fund pilot grants.  This funding will also ensure that the serum bank created by the MGFA’s transformative grant will continue.  

MGFA is proud to represent the MG Community as a member of MG Net, and has committed $250,000 of funding ($50,000 for each year) to support the project.  This commitment from MGFA, as well as that of Illinois-based Conquer MG, was instrumental in demonstrating the support of the MG Community for the project—an essential component of the criteria for funding established by the NIH. Press release available here.

 

Diabetes drug Metformin May Have Novel Therapeutic Potential to Treat MG

The study, "Metformin attenuates autoimmune disease of the neuromotor system in animal models of myasthenia gravis", published by International Immunopharmacology, used a mouse model to investigate the therapeutic potential of metformin on autoimmune myasthenia gravis. Researchers showed that oral administration of metformin diminished the onset, reduced clinical severity and led to a reduction in mortality in experimental autoimmune myasthenia gravis rats. 

 

Zilucoplan Receives Orphan Drug Status for Treating MG 

Ra Pharmaceuticals announced that the U.S. Food and Drug Administration (FDA) granted Orphan Drug Designation to zilucoplan for the treatment of myasthenia gravis. Ra Pharma is developing zilucoplan, a self-administered macrocyclic peptide inhibitor of complement component 5 (C5), for the treatment of generalized myasthenia gravis (gMG) and other rare, tissue-based complement-mediated diseases.

 

MG Metabolic Profile May Be Used to Predict Course and Treatment for MG

"Beyond the antibodies: serum metabolimic profiling of myasthenia gravis", published by Metabolomics, uses a profiling approach as a potential strategy for identifying biomarkers unique to myasthenia gravis. Comparisons between patients with MG vs. HC (healthy controls), and RA (rheumatoid arthritis) vs. HC were made using univariate and multivariate statistics.

 

Patterns of Muscle Weakness Vary Widely for MG Patients

"Heterogeneity and shifts in distribution of muscle weakness in myasthenia gravis", published by Neuromuscular Disorders, analyzes the distribution of muscle weakness in 225 AChR MG patients over time. The study identified phenotypes: ocular, bulbar, neck/ limbs/ respiratory, or a combination. MG patients frequently shift between phenotypes. These variations found in AChR MG suggest that other factors aside from the ACHR antibody mediated immune response are important in determining the disease expression of MG. 

 

Poorer Nerve Cell Response in Diagnostic Tests May Prompt More Aggressive Treatment Recommendations for MG

Patients who initially showed greater fluctuations in the electric signal at the neuromuscular junction and lower electrical signals (reduced by 20% or more) were more frequently positive for autoantibodies and had generalized disease. These patients were also classified as having more severe disease, having higher quantitative (above 10.5) myasthenia gravis score (QMGS) at baseline, compared to patients with better electrophysiological test results. See here for the full article from the Canadian Journal of Neurological Sciences, "Baseline Decrement in Patients with Mild Myasthenia Gravis Predicts Immunomodulation Treatment".

 

MGFA Statement on Marijuana and MG

Several states have legalized the use of marijuana for medical and/or recreational use.  Can marijuana or chemicals extracted or based upon components of marijuana help people with MG?  Let’s consider what is currently known about medical benefits of marijuana. In researching this topic, members of the MGFA Medical and Scientific Advisory Board (MSAB), reviewed the scientific literature and the information available from reputable sources such as the National Institutes of Health, the American Academy of Neurology, the American Neurological Association and the American Medical Association. For more detail and our full statement, see here

 

Adverse Events in Placebo-Treated MG Patients do not Result in Higher Clinical Trial Dropout Rate

The study, "Nocebo effect in myasthenia gravis: systematic review and meta-analysis of placebo-controlled clinical trials", published in the journal Acta Neurologia Belgica, is a meta-analysis of adverse events experienced by patients with myasthenia gravis following placebo treatment. The study demonstrates a low nocebo dropout rate in MG comapted to central nervous system disorders. 

 

MG Patients with Coexisting Autoimmune Diseases do not have Higher Disease Burden 

While many MG patients were affected by fatigue, sleepiness, depression and anxiety, the study, "Impact of autoimmune comorbidity on fatigue, slepiness and mood in myasthenia gravis",  does not suggest that coexisting autoimmune diseases substantially contribute to the magnitude of these cumbersome comorbid symptoms. However, the higher frequency of steroid treatment may have counterbalanced the effects of the autoimmune comorbidity. 

 

Zilucoplan, a Subcutaneously Self-Administered Peptide Inhibitor of Complement Component 5 (C5), for the Treatment of Generalized Myasthenia Gravis: Results of Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial and Open-Label Long-Term Extension 

Results of the Phase 2 study were presented at the 2019 American Academy of Neurology Annual Meeting in May: 
Presentation

Poster 

 

Retrospective Study to Determine the Efficacy of Rituximab in Treating Myasthenia Gravis

A group of scientists in Austria conducted a study to determine the efficacy of rituximab in treating myasthenia gravis. The study, titled, “High efficacy of rituximab for myasthenia gravis: a comprehensive nationwide study in Austria” looked at 56 patients and studied their response to rituximab, finding that 26.4% of the patients studied were in remission after three months of treatment. In this retrospective study on RTX for MG, the largest to date, RTX appeared safe, efficacious and fast acting. Benefit from RTX was greatest in MuSK ab + MG.

 

A World Without MG