Author: Rachael Hansford

CIDP – FDA approval of HYQVIA

Posted on January 17, 2024 by - Neuroimmunology

FDA approves Takeda’s Immune Globulin Infusion, Hyqvia

16 January, 2024;

The U.S. Food and Drug Administration (FDA) has approved HYQVIA® [Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase] for the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) as maintenance therapy to prevent the relapse of neuromuscular disability and impairment in adults. HYQVIA first received approval in the U.S. in 2014 for the treatment of primary immunodeficiency (PI) in adults, which has since been expanded to include children 2-16 years old.1

HYQVIA is the only FDA-approved combination of immunoglobulin (IG) and hyaluronidase, which makes it a facilitated subcutaneous immunoglobulin (SCIG) infusion. For adults with CIDP, HYQVIA can be infused up to once monthly (every two, three or four weeks) due to the hyaluronidase component, which facilitates the dispersion and absorption of large IG volumes in the subcutaneous space between the skin and the muscle. Because it is delivered subcutaneously, HYQVIA can be administered by a healthcare professional in a medical office, infusion centre or at a patient’s home. In addition, it can be self-administered after appropriate patient or caregiver training.1

“With the FDA approval of HYQVIA for CIDP, which builds on our expertise in rare neuroimmunological and neuromuscular disorders, we can now offer a personalised maintenance treatment option for adults with this debilitating disease,” said Giles Platford, President of Takeda’s Plasma-Derived Therapies Business Unit. “Research and clinical experience have shown that IG therapy is effective as maintenance treatment in adults with CIDP, and we hope that this approval for HYQVIA is the first of several around the world as we strive to deliver our broad and diverse IG portfolio to more people with complex neuroimmunological diseases.”

This approval is based on results from a randomised, double-blinded, placebo-controlled study (ADVANCE-CIDP 1) and a single-arm, open-label, extension study (ADVANCE-CIDP 3) that evaluated the efficacy and safety of HYQVIA as a maintenance therapy in adults with CIDP. The efficacy evaluation included 122 adults from ADVANCE-CIDP 1 with a confirmed diagnosis of CIDP and who had remained on a stable dosing regimen of intravenous immunoglobulin (IVIG) therapy for at least three months prior to screening. The analysis of the primary endpoint demonstrated a statistically significant difference between the relapse rates in the HYQVIA group (N=57, 14.0%) compared to the placebo group (N=65, 32.3%) (p=0.0314). The treatment difference of -18.3% (two-sided 95% CI: -32.1%, -3.1%) indicated that HYQVIA demonstrated superiority over placebo in preventing relapse of CIDP.1

The safety of HYQVIA in adults with CIDP was evaluated across ADVANCE-CIDP 1 (N=62) and ADVANCE-CIDP 3 (N=79). The most common adverse reactions observed in >5% of study subjects in clinical studies of HYQVIA for CIDP were local reactions, headache, pyrexia, nausea, fatigue, erythema, pruritus, increased lipase, abdominal pain, back pain, and pain in extremity.1

We hope that this approval for HYQVIA is the first of several around the world as we strive to deliver our broad and diverse IG portfolio to more people with complex neuroimmunological diseases.

Giles Platford, President of Takeda’s Plasma-Derived Therapies Business Unit

CIDP is a rare, acquired, immune-mediated neuromuscular disorder affecting the peripheral nervous system.2,3 It is typically characterised by progressive, symmetric symptoms such as weakness, tingling or loss of feeling in distal and proximal limbs, loss of reflexes and difficulty walking.3 Because its symptoms may overlap with other rare, neuromuscular conditions, CIDP is often misdiagnosed.4 The mechanism of action of IG in the treatment of CIDP in adults has not been fully elucidated but may include immunomodulatory effects.1 The role of IG therapy as maintenance treatment in CIDP has been well-established and is the guidelines-based standard of care for this complex and heterogeneous condition.5 However, there are aspects of IVIG treatment that can be challenging for patients such as long treatment duration associated with high IG volumes, potential for venous access challenges, and infusion setting limitations.5

“While it is considered the standard-of-care for maintenance treatment of adults with CIDP, IVIG infusions may be challenging for some patients and their caregivers,” said Lisa Butler, executive director, GBS-CIDP Foundation International. “We’re excited that this therapy could offer some adults with CIDP an alternative subcutaneous option that may address some of these challenges and help personalise treatment.”

HYQVIA is now available as a maintenance therapy for adult patients with CIDP in the U.S.

In December 2023, Takeda announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of HYQVIA as maintenance therapy in patients with CIDP after stabilisation with IVIG. The European Commission (EC) will consider the CHMP positive opinion when determining the potential marketing authorisation for HYQVIA for CIDP throughout the European Union.6

References

  1. HYQVIA® [Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase] U.S. Prescribing Information.
  2. GBS CIDP Foundation International. Voice of the Patient Report. August 26, 2022. http://www.gbs-cidp.org. Accessed August 2022.
  3. Dalakas MC. Nat Rev Neurol. 2011;7(9):507–17.
  4. Broers MC, Bunschoten C, Nieboer D, Lingsma HF, Jacobs BC. Eur J Neurol. 2021;28(6):2065–2073.
  5. Van den Bergh P, Van Doorn PA, Hadden RD, et al. Eur J Neurol. 2021;28(11):3556–3583.
  6. European Medicines Agency. HyQvia 100 mg/mL solution for infusion for subcutaneous use Summary of Product Characteristics. Available at https://www.ema.europa.eu/en/documents/product-information/hyqvia-epar-product-information_en.pdf

RYSTIGGO®▼ (rozanolixizumab) EC approval

Posted on January 8, 2024 by - Myasthenia Gravis

UCB announces European Commission approval of RYSTIGGO®▼ (rozanolixizumab) for the treatment of adults with generalized myasthenia gravis in Europe

  • European approval of RYSTIGGO® (rozanolixizumab) granted as an add-on to standard therapy for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive1
  • Approval of this orphan medicinal product is based on pivotal Phase 3 MycarinG study in gMG,2 which demonstrated that treatment with rozanolixizumab resulted in statistically significant and clinically meaningful improvements in gMG-specific outcomes compared to placebo,2 including everyday activities such as breathing, talking, swallowing, and being able to rise from a chair3
  • Rozanolixizumab is the first therapy approved in Europe for adults with AChR or MuSK antibody-positive gMG, the two most common subtypes of gMG 
  • The decision follows EC approval for UCB’s ZILBRYSQ®▼ (zilucoplan) in Europe for the treatment of adult patients with gMG, alongside U.S. FDA and Japanese MHLW approvals of rozanolixizumab and zilucoplan for the treatment of gMG in adult patients in 2023.4,5,6,7
  • UCB is the first and only company to offer a gMG-focused portfolio, that provides patients and clinicians the option of targeted therapies for both anti-AChR and anti-MuSK antibody-positive gMG

8th January 2024: UCB, a global biopharmaceutical company, today announced that the European Commission (EC) granted a marketing authorisation for RYSTIGGO® (rozanolixizumab) on 5th January 2024 as an add-on to standard therapy for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive1.

Rozanolixizumab 140 mg/ml solution for injection is a humanised IgG4 monoclonal antibody that binds to the neonatal Fc receptor (FcRn) resulting in the reduction of circulating IgG.2 It is the first therapy approved in Europe for adults with anti-AChR or anti-MuSK antibody-positive gMG, the two most common subtypes of gMG.

In December 2023, the EC also granted a marketing authorisation for UCB’s ZILBRYSQ®▼(zilucoplan) as an add-on to standard therapy for the treatment of gMG in adult patients who are anti-AChR antibody-positive4. Zilucoplan is a once-daily subcutaneously (SC) injected, self-administered peptide inhibitor of complement component 5 (C5 inhibitor).8

In progressing a portfolio of medicines for the treatment of gMG, with the aim of providing HCPs the option of addressing either complement activation or pathogenic antibodies for appropriate patients, UCB hopes to offer a comprehensive portfolio of targeted therapeutics, embodying a commitment to addressing the gMG community’s unmet needs.

With the EC approval of rozanolixizumab, alongside their recent approval of zilucoplan, I’m very excited that our gMG portfolio is now approved for use by healthcare professionals across Europe. This represents another important milestone in our ambition to deliver new and additional patient value to the gMG community and continues our launch trajectory. We believe there is still a significant unmet need within the gMG community which can be addressed by bringing differentiated, generally well-tolerated, and effective treatment options to patients that address key aspects of gMG pathophysiology.

Jean-Christophe Tellier, CEO, UCB

EC approval of rozanolixizumab is supported by safety and efficacy data from the pivotal Phase 3 MycarinG study (NCT03971422), published in The Lancet Neurology in May 2023.2

This announcement follows approvals of rozanolixizumab and zilucoplan by the Japanese Ministry of Health, Labour and Welfare (MHLW) for treatment of gMG in adult patients (only for patients who inadequately respond to steroids or other immunosuppressants), approval of rozanolixizumab by the U.S. Food and Drug Administration (FDA) for the treatment of gMG in adult patients who are anti-AChR or anti-MuSK antibody positive , and approval of zilucoplan by the FDA for the treatment of gMG in adult patients who are AChR antibody-positive. 7,5,6

Orphan designation was granted by the European Commission in 2020 to rozanolixizumab for the treatment of myasthenia gravis and maintained after having received the positive CHMP Opinion.9

The approval of rozanolixizumab from the EC is valid in all EU member states, as well as in the European Economic Area (EEA) countries Iceland, Liechtenstein, and Norway. 

UCB is committed to making rozanolixizumab available to patients as quickly as possible and anticipates European availability will commence in the first quarter of 2024.

▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

References:

  1. Rozanolixizumab EU SmPC https://www.ema.europa.eu/en. Accessed January 2024.
  2. Bril V. Efficacy and safety of rozanolixizumab in patients with generalised myasthenia gravis: a randomised, double-blind, placebo-controlled, adaptive Phase 3 study MycarinG study. Lancet Neurol. 2023;22(5):383-94.
  3. Wolfe Gl, et al. Myasthenia gravis activities of daily living profile. Neurology. 1992;52(7):1487-9.
  4. Zilucoplan EU SmPC https://www.ema.europa.eu/en/documents/product-information/zilbrysq-epar-product-information_en.pdf. Accessed January 2024.
  5. RYSTIGGO® U.S. Prescribing Information https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761286s000lbl.pdf. Accessed January 2024.
  6. ZILBRYSQ® U.S. Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216834s000lbl.pdf. Accessed January 2024
  7. Japan MHLW, 25 September 2023.
  8. Howard JF Jr, et al. Safety and efficacy of zilucoplan in patients with generalised myasthenia gravis (RAISE): a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Neurol. 2023;22(5):395-406. 
  9. European Medicines Agency. 2020. EU/3/20/2272: Orphan designation for the treatment of myasthenia gravis. https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu3202272. Accessed January 2024.

Gait freezing: soft robotic, wearable device improves walking for individual with Parkinson’s disease

Posted on January 5, 2024 by - Parkinson’s Disease

Robotic exosuit eliminated gait freezing

5 January, 2024; Gait freezing is one of the most common and debilitating symptoms of Parkinson’s disease, with people suddenly losing the ability to move their feet, often mid-stride, resulting in a series of staccato stutter steps that get shorter until they stop altogether. These episodes are one of the biggest contributors to falls among people living with Parkinson’s disease. Freezing is treated with a range of pharmacological, surgical or behavioural therapies, none of which are particularly effective. 

Researchers from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) and the Boston University Sargent College of Health & Rehabilitation Sciences have used a soft, wearable robot to help a person living with Parkinson’s walk without freezing. The robotic garment, worn around the hips and thighs, gives a gentle push to the hips as the leg swings, helping the patient achieve a longer stride. 

The device completely eliminated the participant’s freezing while walking indoors, allowing them to walk faster and further than they could without the garment’s help. 

“We found that just a small amount of mechanical assistance from our soft robotic apparel delivered instantaneous effects and consistently improved walking across a range of conditions for the individual in our study,” said Conor Walsh, the Paul A. Maeder Professor of Engineering and Applied Sciences at SEAS and co-corresponding author of the study. 

The research demonstrates the potential of soft robotics to treat this frustrating and potentially dangerous symptom of Parkinson’s disease and could allow people living with the disease to regain not only their mobility but their independence. 

The research is published in Nature Medicine.

For over a decade, Walsh’s Biodesign Lab at SEAS has been developing assistive and rehabilitative robotic technologies to improve mobility for individuals’ post-stroke and those living with ALS or other diseases that impact mobility. Some of that technology, specifically an exosuit for post-stroke gait retraining, received support from the Wyss Institute for Biologically Inspired Engineering, and was licensed and commercialised by ReWalk Robotics.

Screen shot of Harvard Biodesign Lab website

In 2022, SEAS and Sargent College received a grant from the Massachusetts Technology Collaborative to support the development and translation of next-generation robotics and wearable technologies. The research is centered at the Move Lab, whose mission is to support advances in human performance enhancement with the collaborative space, funding, R&D infrastructure, and experience necessary to turn promising research into mature technologies that can be translated through collaboration with industry partners.

This research emerged from that partnership.

“Leveraging soft wearable robots to prevent freezing of gait in patients with Parkinson’s required a collaboration between engineers, rehabilitation scientists, physical therapists, biomechanists and apparel designers,” said Walsh, whose team collaborated closely with that of Terry Ellis,  Professor and Physical Therapy Department Chair and Director of the Center for Neurorehabilitation at Boston University. 

The team spent six months working with a 73-year-old man with Parkinson’s disease, who — despite using both surgical and pharmacologic treatments — endured substantial and incapacitating freezing episodes more than 10 times a day, causing him to fall frequently. These episodes prevented him from walking around his community and forced him to rely on a scooter to get around outside. 

In previous research, Walsh and his team leveraged human-in-the-loop optimisation to demonstrate that a soft, wearable device could be used to augment hip flexion and assist in swinging the leg forward to provide an efficient approach to reduce energy expenditure during walking in healthy individuals.  

Here, the researchers used the same approach but to address freezing. The wearable device uses cable-driven actuators and sensors worn around the waist and thighs. Using motion data collected by the sensors, algorithms estimate the phase of the gait and generate assistive forces in tandem with muscle movement.

The effect was instantaneous. Without any special training, the patient was able to walk without any freezing indoors and with only occasional episodes outdoors. He was also able to walk and talk without freezing, a rarity without the device. 

“Our team was really excited to see the impact of the technology on the participant’s walking,” said Jinsoo Kim, former PhD student at SEAS and co-lead author on the study. 

During the study visits, the participant told researchers: “The suit helps me take longer steps and when it is not active, I notice I drag my feet much more. It has really helped me, and I feel it is a positive step forward. It could help me to walk longer and maintain the quality of my life.” 

“Our study participants who volunteer their time are real partners,” said Walsh. “Because mobility is difficult, it was a real challenge for this individual to even come into the lab, but we benefited so much from his perspective and feedback.” 

The device could also be used to better understand the mechanisms of gait freezing, which is poorly understood. 

“Because we don’t really understand freezing, we don’t really know why this approach works so well,” said Ellis. “But this work suggests the potential benefits of a ’bottom-up’ rather than ’top-down’ solution to treating gait freezing. We see that restoring almost-normal biomechanics alters the peripheral dynamics of gait and may influence the central processing of gait control.”

The research was co-authored by Jinsoo Kim, Franchino Porciuncula, Hee Doo Yang, Nicholas Wendel, Teresa Baker and Andrew Chin. Asa Eckert-Erdheim and Dorothy Orzel also contributed to the design of the technology, as well as Ada Huang, and Sarah Sullivan managed the clinical research. It was supported by the National Science Foundation under grant CMMI-1925085; the National Institutes of Health under grant NIH U01 TR002775; and the Massachusetts Technology Collaborative, Collaborative Research and Development Matching Grant.

Preventing migraine with CGRP

Posted on December 12, 2023 by - Headache

PRODROME trial shows CGRP in migraine prodrome can stop headache and reduce severity

11 December, 2023: Research shows that taking a specific class of migraine medication during the prodromal phase reduces the development and severity of the subsequent headache. In the randomised, placebo-controlled PRODROME trial, treatment with ubrogepant (Ubrelvy) 100 mg, one of the new CGRP receptor antagonists, during the prodrome prevented the development of moderate/severe headache at both 24 hours and 48 hours post-dose. The medication also reduced headache of any intensity within 24 hours and functional disability compared with placebo.

The findings were presented at 17th European Headache Congress (EHC) and were also recently published online in The Lancet. 

[Read clinical article: Monoclonal CGRP- (R) antibodies for the prevention of migraine by Uwe Reuter in ACNR]

The prodrome, the earliest stage of a migraine attack, consists of various symptoms including sensitivity to light, fatigue, mood changes, cognitive dysfunction, craving certain foods, and neck pain, which can occur several hours or days before onset.

At present there isn’t much which can be done to prevent the headache. Triptans are only recommended during the headache phase, due to the risk of medication overuse headache and the fact they don’t work during the prodromal phase. However, ubrogepant and other members of the “gepant” class do not seem to have the tendency for medication overuse problems. Instead, they seem to have a preventative effect and also reduce severity. The incidence of moderate to severe headache was almost halved when ubrogepant was taken in the prodrome.

The ‘gepants’ are a class of medication that can be used in almost any way in migraine — to treat an acute migraine headache, to prevent migraine if taken chronically, and now we see that they can also stop a migraine from developing if taken during the initial prodromal phase. That’s unique for a migraine medication.

Peter Goadsby, Study Investigator

Goadsby noted that the prodromal phase of migraine has only just started to be explored, with functional imaging studies showing that structural brain changes occur during this phase. 

He said the current study opens up a whole new area of interest, emphasising the clinical value of identifying the prodrome in individuals with migraine, better characterising the symptomology of the prodrome and understanding more about how to treat it.

The trial

The PRODROME trial was conducted at 75 sites in the United States in 518 patients who had at least a 1-year history of migraine with or without aura and a history of two to eight migraine attacks per month with moderate to severe headache in each of the 3 months before study entry. 

Participants underwent a rigorous screening period during which they were required to show that they could identify prodromal symptoms that were reliably followed by migraine headache within 1-6 hours.

They were randomly assigned to receive either placebo to treat the first qualifying prodrome event and ubrogepant 100 mg to treat the second qualifying prodrome event or vice versa, with instructions to take the study drug at the onset of the prodrome event.

Efficacy assessments during the double-blind treatment period were recorded by the participant in an electronic diary. On identifying a qualifying prodrome, the patient recorded prodromal symptoms, and was then required to report the absence or presence of a headache at regular intervals up to 48 hours after the study drug dose. If a headache was reported, participants rated the intensity as mild, moderate, or severe and reported whether rescue medication was taken to treat it.

The primary endpoint was absence of moderate or severe intensity headache within 24 hours after study-drug dose. This occurred after 46% of 418 qualifying prodrome events that had been treated with ubrogepant and after 29% of 423 qualifying prodrome events that had been treated with placebo (odds ratio, 2.09; 95% CI, 1.63 – 2.69; P < .0001). 

The PRODROME study was funded by AbbVie.

[Read more Headache articles in ACNR]

Evobrutinib in relapsing Multiple sclerosis

Posted on December 11, 2023 by - Multiple Sclerosis

Results from the EVOLUTION clinical trials showed evobrutinib did not meet its primary endpoint of annualised relapse rate for up to 156 weeks compared to oral teriflunomide in both studies

In two Phase III trials, evolutionRMS 1 and evolutionRMS 2, the compound known as evobrutinib failed to beat Sanofi’s established Aubagio in reducing MS relapse rates, Merck said in a statement on 5th December 2023.

Merck was seen as ahead of Sanofi, Novartis and Roche in efforts to develop more MS drugs targeted at Bruton’s tyrosine kinase (BTK) inhibitors. It is designed to more selectively block the cells that drive the harmful autoimmune reaction behind MS.

The company will complete a full evaluation of the data from the clinical trials and will work with investigators on the future presentation and publication of the results.

In this podcast, Expert Patient Dominic Shadbolt from www.themsguide.com talks to Aaron Boster about the nuances of trials, what this means to the other companies who have BTKs in Phase 3 trial development (Roche, Sanofi) and why it isn’t the end for either evobrutinib or the class as a whole.

Migraine and obesity

Posted on December 7, 2023 by - Headache

New Post Hoc Phase 3 Data Analysis Shows AJOVY® (fremanezumab) Reduced Migraine Attacks in Adults with Migraine and Co-morbid Obesity

  • AJOVY® (fremanezumab) efficacy and safety demonstrated in migraine patients with obesity in post hoc analysis of HALO-LTS[i] and FOCUS[ii] Phase 3 studies
  • Obesity is a known risk factor for migraine and is frequently associated with an increase in migraine frequency, severity and disability[iii]
  • Data revealed at the 17th European Headache Congress, Barcelona, Spain

6th December, 2023: Teva Pharmaceuticals has announced that a post hoc analysis [iv] of two Phase 3 clinical studies presented at the European Headache Congress has shown the effectiveness of the migraine prevention treatment AJOVY® (fremanezumab) in reducing migraine attacks in patients with migraine and co-morbid obesity.

Migraine and obesity are both associated with high levels of disability.3 The 2021 Health Survey for England5 estimates that 25.9% of adults in England are obese and a further 37.9% are overweight, with people aged 45-74 most likely to be overweight or obese. In Europe, it is estimated that 59% of people are either overweight or obese, with almost a quarter (23%) of adults living with obesity.6

A higher body mass index (BMI) is frequently associated with increased migraine prevalence and severity, and an increased number of adverse effects.3 As such, assessing the efficacy and safety of migraine preventative treatment in patients with obesity can help guide migraine management and treatment decisions.

The post hoc analysis of the HALO-LTS1 and FOCUS 2 Phase 3 studies compared the safety and efficacy of fremanezumab migraine preventive treatment in obese migraine patients versus normal weight migraine patients for a period of six months. Obesity was defined as having a Body Mass Index (BMI) ≥30 kg/m2 (BMI-high, 578 patients), and normal weight patients with a BMI <30 kg/m2 (BMI-normal, 1859 patients).

[Read ACNR headache articles]

The analysis showed that the efficacy of fremanezumab was the same in migraine patients with BMI-high vs BMI-normal:

  • At baseline, monthly migraine days in migraine patients with BMI-high vs BMI-normal were 13.7 vs 13.6 respectively
  • After 6 months of treatment with fremanezumab, monthly migraine days in migraine patients with BMI-high vs BMI-normal was reduced to 6.8 vs 7.2 respectively

Furthermore, adverse events (AEs) in patients with obesity were similar to AEs in non-obese patients treated with fremanezumab.

This analysis is encouraging as it shows fremanezumab can reduce migraine attacks as effectively in obese patients as it does in patients of normal weight. Considering the higher burden of migraine in patients with co-morbid obesity, it is important for treatments to demonstrate efficacy and safety in migraine patients with this particular comorbidity.

Lead study author, Consultant Neurologist Dr Pablo Irimia Sieira, of Clinica Universidad de Navarra, Pamplona, Spain

AJOVY® (fremanezumab), a humanised monoclonal antibody (mAb) developed by Teva Pharmaceuticals, selectively targets the calcitonin gene-related peptide (CGRP) and is approved for the prevention of migraine in adults who have at least four migraine days per month.

References

[i] HALO-LTS, NCT02638103

[ii] FOCUS study NCT03308968

[iii] Westgate CSJ, et al. Understanding the link between obesity and headache- with focus on migraine and idiopathic intracranial hypertension. J Headache Pain. 2021;22(1):123.

[iv] Sieria Pablo, et al. Efficacy and Safety of Fremanezumab in Patients with Migraine and Obseity: Post Hoc Analysis of the Phase 3 HALO-LTS and FOCUS Clinical Trails. Presented at the European Headache Congress December 2023. PO35 Poster

5 UK Parliament House of Commons Library. Obesity Data. Available at: https://commonslibrary.parliament.uk/research-briefings/sn03336/#:~:text=Adult%20obesity%20in%20England,is%20classified%20as%20’overweight Accessed: Nov 2023

6 WHO Regional European Obesity Report 2022

EC approves adult generalised Myasthenia gravis treatment

Posted on December 6, 2023 by - Myasthenia Gravis

UCB announces European Commission approval of ZILBRYSQ[®]▼ (zilucoplan) 

  • European approval of ZILBRYSQ® (zilucoplan) granted as an add-on to standard therapy for the treatment of generalised Myasthenia Gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody-positive1
  • Zilucoplan is the first once-daily subcutaneous, targeted C5 complement inhibitor for gMG.2 
  • Approval supported by pivotal Phase 3 RAISE study in gMG2 which demonstrated treatment with zilucoplan resulted in statistically significant improvements in MG-specific efficacy outcomes compared to placebo
  • European approval for zilucoplan follows approvals in U.S. and Japan earlier in 20233,4
  • Alongside rozanolixizumab, which was recently approved in U.S. and Japan for the treatment of gMG,4,5 and which has received a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP),6 zilucoplan is part of UCB’s portfolio of two different medicines for gMG, each with a distinct mechanism of action and with potential to offer physicians new and additional treatment choices

4th December, 2023: UCB, a global biopharmaceutical company, today announced that the European Commission (EC) has granted a marketing authorisation for ZILBRYSQ® (zilucoplan) as an add-on to standard therapy for the treatment of generalised myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody-positive.1 

Zilucoplan is the first once-daily subcutaneous (SC), targeted peptide inhibitor of complement component 5 (C5) inhibitor for gMG, and the only C5 inhibitor approved for self-administration by adult patients with AChR antibody-positive gMG.2 

As a C5 inhibitor, zilucoplan inhibits complement-mediated damage to the neuromuscular junction through its targeted dual mechanism of action.2 Benefits of SC self-injection can include reduced traveling time to and from hospitals, decreased interference with work obligations, and increased independence.2 

Unlike monoclonal antibody C5 inhibitors, as a peptide, zilucoplan can be used concomitantly with intravenous immunoglobulin and plasma exchange, without the need for supplemental dosing.2 

The EC approval of zilucoplan is supported by safety and efficacy data from the RAISE study (NCT04115293), published in The Lancet Neurology in May 2023.2 The RAISE study was a multi-centre, phase 3, randomised, 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. Patients were randomised in a 1:1 ratio to receive daily subcutaneous (SC) injections of 0.3 mg/kg zilucoplan or placebo for 12 Weeks. The study demonstrated that zilucoplan delivered rapid, consistent, clinically meaningful and statistically significant improvements in different patient- and clinician-reported outcomes at week 12 in a broad population of adult patients with mild-to-severe anti-AChR antibody-positive gMG.2  

As included within the zilucoplan EU Summary of Product Characteristics, the most frequently reported adverse reactions were injection site reactions (injection site bruising (13.9%) and injection site pain (7.0%)) and upper respiratory tract infections (nasopharyngitis (5.2%), upper respiratory tract infection (3.5%) and sinusitis (3.5%)).1

European approval of zilucoplan follows approvals by the U.S. Food and Drug Administration (FDA) for the treatment of generalised myasthenia gravis (gMG) in adult patients who are AChR antibody-positive and by the Japanese Ministry of Health, Labour and Welfare (MHLW) for the treatment of gMG in adult patients who inadequately respond to steroids or other immunosuppressants.3,4

gMG is a rare, chronic, heterogeneous, unpredictable autoimmune disease characterised by dysfunction and damage at the neuromuscular junction (NMJ).7,8,9 Several factors are understood to be drivers of gMG disease pathology, including the complement cascade, immune cells and pathogenic Immunoglobulin G (IgG) autoantibodies10.

In AChR antibody-positive gMG, pathogenic AChR autoantibodies (IgG1 and IgG3) initiate the classical complement pathway, which, together with the alternative and lectin complement pathways, converge at C5, leading to MAC (membrane attack complex) deposition, damage to the NMJ, loss of AChRs and subsequent impaired synaptic transmission.9,11 Preventing MAC formation reduces damage to the post-synaptic membrane, reduces disruption of ionic channel conductance and helps to preserve neuromuscular transmission.11 

MG has a global prevalence of 100–350 cases per every 1 million people.8

Alongside approval of zilucoplan, UCB’s neonatal Fc receptor (FcRn) blocker rozanolixizumab recently received a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) as an add-on to standard therapy for the treatment of generalised myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody-positive.6 This follows approvals for rozanolixizumab in similar indications in the U.S. and Japan earlier this year,4,5 further strengthening UCB’s gMG portfolio and the company’s commitment to addressing the gMG community’s unmet needs.

The approval of zilucoplan from the EC is valid in all EU member states, as well as in the European Economic Area (EEA) countries Iceland, Liechtenstein, and Norway. 

UCB is committed to making zilucoplan available to patients as quickly as possible and anticipates European availability will commence in the first quarter of 2024.

▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

References: 

  1. Zilucoplan EU SmPC https://www.ema.europa.eu/en. Accessed December 2023.
  2. Howard JF Jr, et al. Safety and efficacy of zilucoplan in patients with generalised myasthenia gravis (RAISE): a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Neurol. 2023;22(5):395-406. 
  3. ZILBRYSQ® U.S. Prescribing Information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216834s000lbl.pdf. Accessed December 2023.
  4. Data on file: Japan MHLW, 25 September 2023.
  5. Rozanolixizumab-noli FDA approval. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761286s000lbl.pdf. Accessed December 2023.
  6. EMA CHMP rozanolixizumab positive opinion. https://www.ema.europa.eu/en/medicines/human/summaries-opinion/rystiggo#opinion-section. Accessed December 2023.
  7. National Institute of Neurological Disorders and Stroke. 2022. Myasthenia Gravis Fact Sheet. https://www.ninds.nih.gov/myasthenia-gravis-fact-sheet. Accessed December 2023.
  8. Punga AR, et al. Epidemiology, diagnostics, and biomarkers of autoimmune neuromuscular junction disorders. Lancet Neurol. 2022;21(2):176-88.
  9. Howard JF Jr. Myasthenia gravis: The role of complement at the neuromuscular junction. Ann N Y Acad Sci. 2018;1412(1):113‒28. 
  10. Phillips WD, Vincent A. Pathogenesis of myasthenia gravis: Update on disease types, models, and mechanisms. F1000Res. 2016;5:F1000 Faculty Rev-1513.
  11. Mantegazza R, et al. Complement inhibition for the treatment of myasthenia gravis. Immunotargets Ther. 2020;9:317–31.
  12. US Food and Drug Administration. https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=699319. Accessed October 2023.
  13. Myasthenia Gravis Foundation of America. MG Quick Facts. https://myasthenia.org/MG-Education/MG-Quick-Facts. Accessed December 2023.
  14. Juel VC, Massey JM. Myasthenia gravis. Orphanet J Rare Dis. 2007;2:44.
  15. Bril V, et al. Safety and efficacy of rozanolixizumab in patients with generalised myasthenia gravis (MycarinG): a randomised, double-blind, placebo-controlled, adaptive phase 3 study. Lancet Neurol. 2023;22(5):383-94.
  16. RYSTIGGO® U.S. Prescribing Information: https://www.ucb-usa.com/RYSTIGGO-prescribing-information.pdf. Accessed December 2023.

A prodrome for MS?

Posted on December 5, 2023 by - Multiple Sclerosis

Study in Neurology evaluated the associations between diseases and symptoms diagnosed in primary care

The researchers show that, on a population scale, the frequency of disorders such as depression, constipation, and urinary tract infections is associated with a diagnosis of multiple sclerosis five years later. These results outline a prodromal phase of the disease.

Several studies have already suggested that, in some patients, subtle symptoms were present up to ten years before a diagnosis of MS. What remained was to quantify this phenomenon at the population scale to rigorously define a ‘prodromal phase’, i.e. a period during which the disease takes hold discreetly. A better understanding of early symptoms of MS could help researchers pinpoint the exact moment when the inflammatory process that causes lesions in the central nervous system begins.

“One of the major difficulties with multiple sclerosis is that we do not observe a strict correspondence between the severity of lesions on nerve fibres and patients’ symptoms. This considerably limits our ability to predict the course of the disease,” said Professor Céline Louapre, a Neurologist at Pitié-Salpêtrière Hospital and Head of Paris Brain Institute’s clinical investigation center.

“The challenge today is to detect the disease as early as possible, well before the lesions are visible on MRI, in the hope of delaying the onset of disability. Of course, not everyone who has these symptoms will go on to develop MS.’ She added that all four are ‘common’ and ‘could also be signs of other diseases’.

Professor Louapre, accompanied by Octave Guinebretière and Thomas Nedelac, compared the health data of 20,174 patients with multiple sclerosis, 54,790 patients without multiple sclerosis, and 37,814 patients affected by two autoimmune diseases which, like MS, mainly affect women and young adults—namely 30,477 patients with Crohn’s disease and 7,337 with lupus.

The researchers observed that five symptoms were significantly associated with a later diagnosis of multiple sclerosis: depression, sexual disorders, constipation, cystitis, and other urinary tract infections.

“This association was sufficiently robust at the statistical level for us to state that these are early clinical warning signs, probably related to damage to the nervous system, in patients who will later be diagnosed with multiple sclerosis,” Professor Louapre explains. “The overrepresentation of these symptoms persisted and even increased over the five years after diagnosis.”

However, these five symptoms also appeared in the prodromal phase of lupus and Crohn’s disease, which means they are not specific to MS. Most importantly, they are also widespread in healthy people.

A prodrome for MS?

“These signs alone will not be enough to make an early diagnosis, but they will certainly help us better understand the mechanisms of multiple sclerosis—which has many causes—and reconstruct its natural history. Finally, these new data support the idea that the disease begins well before the onset of classic neurological symptoms,” concludes Professor Louapre.

Ubrelvy for migraine: positive phase III data

Posted on December 2, 2023 by - Headache

AbbVie recently announced its publication in The Lancet showing that administration of Ubrelvy (ubrogepant) during the prodrome stage of a migraine can reduce the likelihood of a migraine attack developing. Ubrelvy is the first and only acute migraine treatment that has demonstrated Phase III data in the prodrome stage.

Christie Wong, Pharma Analyst at GlobalData, comments: “The prodrome stage of a migraine occurs between one to six hours before the onset of a migraine attack, and the symptoms can include sensitivity to light and sound, fatigue, and neck stiffness and/or pain. However, not all migraine patients experience prodromal symptoms, and the migraine stages may vary in terms of duration and severity between patients. Thus, Ubrelvy could provide an additional benefit to a subset of migraine patients who are able to identify prodromal symptoms.”

There are many acute treatments for migraine pain relief, but some patients cannot tolerate triptans, which are the gold standard treatment. Ubrelvy could give patients who are able to identify prodromal symptoms the ability to treat migraine during the early stages.

Ubrelvy is the first and only acute migraine treatment that has demonstrated Phase III data in the prodrome stage.

Read headache articles in ACNR’s Headache Archives