Orodispersible film formulation of disease-modifying drug riluzole now available to ALS patients in the UK
Emylif offers an alternative for the 80% of patients who experience difficulty swallowing during the course of their disease1
January 24, 2024: In November 2023, Zambon UK launched Emylif, a new formulation of riluzole in an orodispersible film – for the treatment of adults with amyotrophic lateral sclerosis (ALS). Emylif offers an alternative to the tablet administration of riluzole which can be difficult for patients to take as their disease progresses and they develop dysphagia (difficulty swallowing). Dysphagia occurs in around 80% of ALS patients over the course of their disease1.
Emylif is applied to the tongue and allowed to dissolve, with no need for water, tongue mobility or muscular strength. Studies have demonstrated that this mode of administration is bioequivalent to the tablet form of riluzole.2
Riluzole is the only disease-modifying treatment available to ALS patients in the UK. Currently, it is common practice for carers to crush riluzole tablets in order to administer them to patients who are finding it difficult to swallow tablets.3 Emylif offers a licenced alternative for these patients.
The safety profile of Emylif is very similar to that of other riluzole formulations, with the exception of oral hypoesthesia (numbness in the mouth). It is common for patients to experience mild and transient oral hypoesthesia which can last for an average of around 40 minutes.5 In a small-scale study in ALS patients there was no detrimental effect on swallowing following a single dose of riluzole orodispersible film.6 It is suggested that patients are counselled on the risk of numbness in the mouth so that they are not surprised or concerned if this occurs.
References
Muscaritoli M, Kushta I, Molfino A, Inghilleri M, Sabatelli M, Rossi Fanelli F. Nutritional and metabolic support in patients with amyotrophic lateral sclerosis. Nutrition (2012) 28(10):959-66. doi:10.1016/j.nut.2012.01.011
Di Stefano AFD, Radicioni MM, Segantin A, Gentili A, Baroglio C, Marjanović I, Cattaneo C (2022) Randomised, 2-Sequence, 4-Period Replicate Cross-Over Bioequivalence Study of a New Riluzole Orodispersible Film Vs. A Reference Tablet in Healthy Volunteers. J Bioeq Stud 8(1): 101
Dyer AM, Smith A. Riluzole 5 mg/mL oral suspension: for optimized drug delivery in amyotrophic lateral sclerosis. Drug Des Devel Ther. 2017;11:59-64. https://doi.org/10.2147/DDDT.S123776
Thong MY, Manrique YJ, Steadman KJ. Drug loss while crushing tablets: Comparison of 24 tablet crushing devices. PLoS One. 2018 Mar 1;13(3):e0193683. doi:10.1371/journal.pone.0193683. PMID:29494695; PMCID: PMC5832315
Emylif Summary of Product Characteristics
Wymer J, Apple S, Harrison A, Hill BA. Pharmacokinetics, Bioavailability, and Swallowing Safety With Riluzole Oral Film. Clin Pharmacol Drug Dev 2023 Jan;12(1):57-64.doi:10.1002/cpdd.1168
AboLiSh study demonstrates clinical benefit of injection guidance when treating spasticity with abobotulinumtoxinA
AboLiSh is the first global study to demonstrate the clinical benefit of using injection guidance techniques to improve patient goal attainment
Analyses of study data indicated that patients who are administered treatment with Dysport® (abobotulinumtoxinA) with the use of injection guidance techniques are nearly 3 times more likely overall to achieve their goals
The study highlights that almost 1 in 4 clinicians are not using injection guidance when administering abobotulinumtoxinA
19th January, 2024: Ipsen has announced top line results from its real-world AboLiSh study (NCT04050527), presented at the 7th international TOXINS conference in Berlin, Germany. The study evaluated utilisation and effectiveness of Dysport® (abobotulinumtoxinA) in people living with lower-limb spasticity and found that injection guidance techniques significantly help to improve outcomes and goal attainment in patients.
AboLiSh was a prospective 16-month observational study with a primary endpoint of goal attainment measured by subject centred Goal Attainment Scaling-Leg (LegA) T score. Topline results demonstrated statistically significant improvement in rehabilitation goal attainment in instances where physicians used guidance techniques, such as ultrasound, electrostimulation, electromyography or a combination of techniques, to deliver the first cycle of treatment to patients, compared to those receiving treatment without the use of guidance techniques. Patients who received abobotulinumtoxinA (AboBoNT) injections with the support of injection guidance were nearly 3 times (2.7) more likely overall to achieve their rehabilitation goals.
The AboLiSh study, which assessed 430 patients in 9 countries in Europe, the Americas, Australia and Russia, found that while the majority of clinicians already use guidance techniques, almost 1 in 4 clinicians (23%) administered AboBoNT without guidance, which was associated with reduced goal attainment and could lead to negative consequences, including patient adherence to neurotoxin injections.
“These findings highlight a current lack of consistency in how treatment is being administered to patients and underpin the importance of real-world evidence to inform clinical practice”, said Dr Alberto Esquenazi MD, Director Gait & Motion Analysis Laboratory at Jefferson Moss-Magee Rehabilitation in Philadelphia. “It is crucial that we consistently and routinely use our clinical assessment skills and the injection guidance tools available to us to ensure patients achieve their goals and their treatment is optimised.”
Patients who received abobotulinumtoxinA (AboBoNT) injections with the support of injection guidance were nearly 3 times (2.7) more likely overall to achieve their rehabilitation goals.
Ipsen is committed to further improving patient care for people living with spasticity and the study findings will be used to support Ipsen’s ongoing work to support the training of clinicians on the use of neurotoxin injections for the treatment of spasticity.
“We want to do our part to ensure those receiving treatment with Dysport have access to the best standards of care and are given every opportunity to achieve their goals.” says Sandra Silvestri, Chief Medical Officer, Ipsen. “To help facilitate this we are greatly expanding our Ixcellence program for neurology and rehabilitation specialists in 2024 which will utilise our global network of expert trainers to provide advanced education and knowledge transfer across a broad range of techniques essential to improving outcomes in patients with post stroke spasticity, including anatomy, ultrasound and goal setting.”
Clinicians taking part in the study were not given a protocol for the use of guidance techniques allowing them to treat patients in accordance with their standard practice. Results were determined using a cumulated (mean) Goal Attainment Scaling-Leg (LegA) T score, measuring the difficulty in passive and active muscle function following therapeutic intervention, across treatment cycles for each individual patient. No new safety signals were identified during the trial.
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
HYQVIA® [Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase] U.S. Prescribing Information.
GBS CIDP Foundation International. Voice of the Patient Report. August 26, 2022. http://www.gbs-cidp.org. Accessed August 2022.
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.
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.
Wolfe Gl, et al. Myasthenia gravis activities of daily living profile. Neurology. 1992;52(7):1487-9.
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.
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.
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.
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.
In 2022, SEAS and Sargent College received a grant from the Massachusetts Technology Collaborativeto 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.
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 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).
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.
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).
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.
[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
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.
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.
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.
Sign up to receive our email newsletter with links to the latest content. ACNR is free, thanks to the support of advertisers. The editorial content is peer reviewed and remains completely independent unless clearly specified.
