Special Products Ltd has announced today, 8th September 2017, that Epistatus® 10 mg Oromucosal Solution, Midazolam, is now available to prescribe. The NHS price for a single 10mg in 1mL prefilled syringe is £45.76.
Epistatus® is licensed for use in the treatment of prolonged, acute convulsive seizures in children and adolescents aged 10 to less than 18 years, who have been diagnosed with epilepsy1. Buccal midazolam is recommended by NICE2 for the management of prolonged acute convulsive seizures, and is preferred by most patients and carers compared to the administration of rectal diazepam 3,4.
Epistatus is presented “ready-to-use” in a novel, pre-filled, single-dose syringe, to provide carers with the confidence that they are administering the correct dose1,5. The pre-filled syringe is contained within a specially-designed, secure and tamper-evident protective packaging.
The importance of having an alternate licensed preparation for use in the treatment of prolonged, acute convulsive seizures, especially in a different mode of delivery is an asset to both clinicians and patients.
Dr Rohit Shankar FRCPsych, Consultant in Adult Developmental Neuropsychiatry – CFT and Hon. Associate Clinical Professor – Exeter Medical School
In response to market research and insights, Special Products Ltd has invested heavily in the development of this new bespoke syringe, which is designed to allow simple administration of the dose into the buccal cavity5.
For further information on Epistatus 10 mg oromucosal midazolam pre-filled syringes, please visit http://www.epistatus.co.uk
References:
Epistatus 10mg oromucosal solution. Summary of Product Characteristics.
National Institute for Health and Care Excellence (2012). The epilepsies: the diagnosis and management of epilepsies in adults and children in primary care. NICE clinical guideline CG 137.
Nakken K and Lossius M. Buccal midazolam or rectal diazepam for treatment of residential adult patients with serial seizures or status epilepticus. Acta Neurol Scand: (2011); 124:99-103.
Ashrafi MR et al. Efficacy and usability of buccal midazolam in controlling acute prolonged convulsive seizures in children. European Journal of Paediatric Neurology (2010); doi10.1016/j.ejpn.2010.05.009.
Data on file – Excerpts from Epistatus Patent Application.
CLARITY Extension data published in the MS Journal shows 75% of patients who received 2 annual short courses of Mavenclad (Cladribine Tablets) remained relapse free over 4 years
The majority of patients who experienced Grade 3 lymphopenia in Years 1 and 2 recovered to Grade 0-1 by the end of the study
Merck announced on 5th September 2017 the publication of the results of the CLARITY Extension study in Multiple Sclerosis Journal. The trial, an extension of the Phase III CLARITY study, demonstrated that treatment of patients with relapsing remitting multiple sclerosis (MS) with MAVENCLAD®(Cladribine Tablets) for two years, followed by two years of treatment with placebo, had clinical benefits similar to those seen with four years of treatment with MAVENCLAD®, with a low risk of severe lymphopenia.
The CLARITY Extension study included 806 patients out of 1,184 patients who completed the CLARITY study. The CLARITY Extension study assessed several clinical efficacy endpoints including annualised relapse rate (ARR) and confirmed 3-month Expanded Disability Status Scale (EDSS) progression. The proportion of patients who remained relapse-free at the end of four years was similar to the patients who received Cladribine Tablets 3.5 mg/kg in CLARITY followed by placebo in CLARITY Extension (75.6%), and those who received Cladribine Tablets 3.5 mg/kg in both studies (81.2%). The proportion of patients who remained free of 3-month EDSS progression was also similar between the treatment groups (72.4% vs 77.4%).
Today’s publication further strengthens the evidence for the use of MAVENCLAD® in MS, demonstrating significant, durable benefits in patients not receiving active treatment after the two short courses. The data from this publication and other recent articles suggest that MAVENCLAD® selectively targets the adaptive immune system, particularly the B-cell compartment, and therefore allows the immune system to reconstitute while still preventing MS disease activity in the majority of treated patients.
Prof. Gavin Giovannoni A lead investigator in the CLARITY studies & Chair of Neurology, Barts and The London School of Medicine and Dentistry.
The safety outcomes were comparable to those seen in CLARITY; adverse event rates were similar in patients who received Cladribine Tablets in CLARITY followed by placebo in CLARITY Extension, and those who received Cladribine Tablets in both studies. In CLARITY, patients with active relapsing-remitting multiple sclerosis were randomized to placebo or 1 of 2 cumulative doses of Cladribine Tablets (3.5 or 5.25 mg/kg body weight) for 2 years. In CLARITY Extension, patients were administered placebo or a cumulative dose of Cladribine Tablets 3.5 mg/kg body weight. In patients who received Cladribine Tablets 3.5 mg/kg in CLARITY and placebo in CLARITY Extension, the majority of those who experienced Grade >3 lymphopenia recovered to Grade 0-1 by the completion of CLARITY Extension. Most AEs were classified as mild or moderate.
In the patient group receiving placebo in CLARITY Extension following Cladribine Tablets 3.5 mg/kg in CLARITY, 3.1% of patients discontinued because of AEs. The most frequent AE in patients receiving Cladribine Tablets in the CLARITY Extension study was lymphopenia. The majority of lymphopenia events were classified as mild or moderate, and the majority of patients who experienced lymphopenia Grade ≥3 actually experienced Grade 3 only. In CLARITY Extension, herpes zoster infections were most frequent in patients receiving the highest cumulative dose of Cladribine Tablets (4.8%), however the incidence of herpes zoster in all other treatment groups was similar irrespective of cumulative dose (1.1-2.0%).
Today’s data add to the growing evidence for the use of MAVENCLAD® in patients with relapsing MS. At Merck we are very excited about the difference MAVENCLAD®could make in the lives of patients with this debilitating condition.
Luciano Rossetti Head of Global R&D for the biopharma business of Merck.
In August, the European Commission (EC) granted Marketing Authorisation for MAVENCLAD® for the treatment of adults with highly active relapsing MS* in the 28 countries of the European Union (EU) in addition to Norway, Liechtenstein and Iceland. Merck plans additional filings for regulatory approval in other countries, including the United States.
*Defined as: patients with 1 relapse during the previous year and ≥ 1 T1 Gd+ lesion or ≥ 9 T2 lesions while on therapy with other DMDs; OR patients with ≥ 2 or more relapses in the previous year, whether on DMD treatment or not.
CLARITY Extension Study Design
The CLARITY Extension study involved 806 patients out of 1,184 patients from the CLARITY study, allowing assessment of the effects of 2 years’ additional treatment with Cladribine Tablets beyond the 2-year CLARITY regimen. Patients who received Cladribine Tablets 3.5 mg/kg or 5.25 mg/kg in the CLARITY study were randomised to receive either Cladribine Tablets 3.5 mg/kg or placebo in CLARITY Extension, and patients who received placebo in the original CLARITY study received Cladribine Tablets 3.5 mg/kg in CLARITY Extension.
About MAVENCLAD®
MAVENCLAD® (cladribine tablets) is approved in the European Union for the treatment of highly active relapsing multiple sclerosis[*] (RMS). MAVENCLAD® is a short-course oral therapy that selectively and periodically targets lymphocytes thought to be integral to the pathological process of relapsing MS (RMS). MAVENCLAD® is currently under clinical investigation and not yet approved for the treatment for any use in the United States or Canada. In August 2017, the European Commission (EC) granted marketing authorisation for MAVENCLAD® for the treatment of relapsing forms of multiple sclerosis (RMS) in the 28 countries of the European Union (EU) in addition to Norway, Liechtenstein and Iceland.
The clinical development programme for MAVENCLAD® includes:
The CLARITY (Cladribine Tablets Treating MS Orally) study: a two-year Phase III placebo-controlled study designed to evaluate the efficacy and safety of MAVENCLAD® as a monotherapy in patients with RRMS.
The CLARITY extension study: a two-year Phase III placebo-controlled study following on from the CLARITY study, designed to evaluate the safety and efficacy of MAVENCLAD® over an extended administration for four years.
The ORACLE MS (Oral Cladribine in Early MS) study: a two-year Phase III placebo-controlled study designed to evaluate the efficacy and safety of MAVENCLAD® as a monotherapy in patients at risk of developing MS (patients who have experienced a first clinical event suggestive of MS).
The ONWARD (Oral Cladribine Added ON To Interferon beta-1a in Patients With Active Relapsing Disease) study: a Phase II placebo-controlled study designed primarily to evaluate the safety and tolerability of adding MAVENCLAD® treatment to patients with relapsing forms of MS, who have experienced breakthrough disease while on established interferon-beta therapy.
PREMIERE (Prospective Observational Long-term Safety Registry of Multiple Sclerosis Patients Who Have Participated in Cladribine Clinical Studies) study: interim long-term follow-up data from the prospective registry, PREMIERE, to evaluate the safety and efficacy of MAVENCLAD®. This includes more than 10,000 patient years of data with over 2,700 patients included in the clinical trial program, and more than 10 years of observation in some patients.
EU Indication
MAVENCLAD® (cladribine tablets) is indicated for the treatment of adult patients with highly active relapsing multiple sclerosis (RMS) as defined by clinical or imaging features.
Important EU Safety Information
Contraindications:
MAVENCLAD® is contraindicated in patients with hypersensitivity to the active substance, human immunodeficiency virus (HIV), active chronic infection (tuberculosis or hepatitis), active malignancy, moderate to severe renal impairment (creatinine clearance <60 mL/min), and those who are pregnant and breast-feeding. MAVENCLAD® is also contraindicated in immunocompromised patients, including patients currently receiving immunosuppressive or myelosuppressive therapy.
Special warnings and precautions for use:
The most clinically relevant adverse reactions were lymphopenia and herpes zoster.
Haematological monitoring
Decreases in neutrophil count, red blood cell count, haematocrit, haemoglobin or platelet count compared to baseline values have been observed in clinical studies, although these parameters usually remain within normal limits.
Additive haematological adverse reactions may be expected if cladribine is administered prior to or concomitantly with other substances that affect the haematological profile
Lymphocyte counts must be determined
before initiating MAVENCLAD® in year 1,
before initiating MAVENCLAD® in year 2,
2 and 6 months after start of treatment in each treatment year. If the lymphocyte count is below 500 cells/mm³, it should be actively monitored until values increase again.
Infections
Cladribine can reduce the body’s immune defence and may increase the likelihood of infections. HIV infection, active tuberculosis and active hepatitis must be excluded before initiation of cladribine.
The incidence of herpes zoster was increased in patients on cladribine. If lymphocyte counts drop below 200 cells/mm³, anti-herpes prophylaxis according to local standard practice should be considered during the time of grade 4 lymphopenia. Interruption or delay of MAVENCLAD® may be considered until proper resolution of the infection.
Cases of progressive multifocal leukoencephalopathy (PML) have been reported for parenteral cladribine in patients treated for hairy cell leukaemia with a different treatment regimen.
In the clinical study data base of cladribine in MS (1,976 patients, 8,650 patient years) no case of PML has been reported. However, a baseline magnetic resonance imaging (MRI) should be performed before initiating MAVENCLAD® (usually within 3 months).
Real-world data confirms clinical effectiveness of Zebinix® (eslicarbazepine acetate) for the treatment of partial-onset epilepsy in adults
Eslicarbazepine acetate data shows seizure freedom in 41.3% of patients at 12 months, and retention rates of 73.4%.1
Results from the Euro-Esli study presented 5th September 2017 at the 32ndInternational Epilepsy Congress (IEC) in Barcelona, Spain.1
Bial and Eisai have announced data confirming the effectiveness and tolerability of Zebinix® (eslicarbazepine acetate) in routine clinical practice, thereby complementing evidence from clinical trials.[i] The Euro-Esli study is an exploratory pooled analysis of data from 14 European clinical practice studies, analysing data of 2,058 patients aged between 14-88 years old with partial-onset seizures (POS), with or without secondary generalisation.1 Full results were presented at the IEC in Barcelona, Spain.1
“It is most reassuring to see similar efficacy results with eslicarbazepine acetate in a routine clinical setting compared to that of clinical trials; we can be confident that this treatment is effective amongst the diversity of our ‘real’ epilepsy patients,” explains Dr Vicente Villanueva, Neurologist and Epileptologist, Hospital Universitario y Politécnico La Fe, Valencia, Spain. “Real-world studies like the Euro-Esli study are important because they provide significant insight into how a drug performs in a routine medical setting, allowing us to assess the drug, to ultimately improve patient outcomes.”
Epilepsy is one of the most common neurological conditions in the world, affecting approximately six million people in Europe.2 An epileptic seizure is a clinical manifestation of the condition, thought to result from an abnormal discharge of a set of neurons in the brain.[ii] Seizures can vary in manifestation, from brief lapses of attention to severe and prolonged convulsions.[iii] Depending on the type, seizures may involve one part of the body or the whole body, and may affect consciousness.3 Seizures can also vary in frequency from less than one per year, to several per day.3 Epilepsy has many possible causes but often the cause is unknown.3
The Euro-Esli study (in over 2,000 patients with epilepsy) showed that at 3, 6 and 12 months, seizure freedom rates in patients aged 14-88 years treated with eslicarbazepine acetate were 30.6%, 38.3% and 41.3% respectively. Retention rates were 95.4%, 86.6% and 73.4% and responder rates were 60.9%, 70.5% and 75.6%, respectively.1 There were significant reductions from baseline to final visit in monthly frequencies of total (mean reduction 44.1%), simple partial (78.8%), complex partial (53.1%) and secondarily generalised (80.0%) seizures (p<0.001 for all).1 Adverse events were reported for 34.0% of patients and led to discontinuation of 13.6% of patients.1 The most frequently reported adverse events were dizziness (6.7%), fatigue (5.4%) and somnolence (5.1%).1
These results improve our knowledge and understanding around the use of eslicarbazepine acetate in routine clinical practice and strengthen Bial’s commitment to developing and delivering beneficial treatment options for people living with epilepsy António Portela, CEO of Bial
These data underscore our commitment to our anti-epileptic drug product portfolio. We will continue to invest both in clinical trials and the generation of real-world evidence to improve the lives of patients living with epilepsy Neil West, Vice President EMEA, Global Neurology Business Unit at Eisai
Eslicarbazepine acetate is indicated as monotherapy in the treatment of POS, with or without secondary generalisation, in adults with newly diagnosed epilepsy; and as adjunctive therapy in adults, adolescents, and children aged above six years, with POS with or without secondary generalisation.[iv]
About the Euro-Esli study1
The Euro-Esli study was a large, exploratory, pooled analysis of real-world data from 14 European clinical practice studies, including data from 2,058 patients (52.1% male; mean age 44 years; mean epilepsy duration 20.9 years). Retention and effectiveness were assessed after 3, 6 and 12 months of treatment with eslicarbazepine acetate. Effectiveness assessments comprised percentage reduction from baseline in monthly seizure frequency, responder rate (≥50% seizure frequency reduction) and seizure freedom rate (seizure freedom at least since prior visit). Safety and tolerability were assessed by evaluating adverse events (AEs).
REFERENCES
[i] Villanueva V, et al. (2017) A European audit of real-world use of eslicarbazepine acetate as a treatment for partial-onset seizures: the Euro-Esli study. International Epilepsy Congress (IEC) 2017; Barcelona, Spain, Poster p0918
[v] Hebeisen S, et al. (2015) Eslicarbazepine and the enhancement of slow inactivation of voltage-gated sodium channels: A comparison with carbamazepine, oxcarbazepine and lacosamide. Neuropharmacology. 89, 122-135
[vi] Elger C, et al. (2007) Eslicarbazepine acetate: A double-blind, add-on, placebo-controlled exploratory trial in adult patients with partial-onset seizures. Epilepsia. 48, 497-504.
[vii] Elger C, et al. (2009) Efficacy and safety of eslicarbazepine acetate as adjunctive treatment in adults with refractory partial onset seizures: A randomised, double-blind, placebo-controlled, parallel-group phase III study.Epilepsia. 50, 454-63.
[viii] Ben-Menachem E, et al. (2010) Eslicarbazepine acetate as adjunctive therapy in adult patients with partial epilepsy. Epilepsy Research. 89(2-3), 278-85.
[ix] Gil-Nagel A, et al. (2009) Efficacy and safety of 800 and 1200 mg eslicarbazepine acetate as adjunctive treatment in adults with refractory partial-onset seizures. Acta Neurologica Scandinavica. 120, 281-87.
First oral short-course treatment for highly active relapsing multiple sclerosis (RMS) now approved in Europe
Mavenclad has shown sustained clinical efficacy for up to 4 years with a maximum of 20 days of oral treatment over 2 years
Marketing authorisation includes the 28 countries of the European Union (EU), with first launches in the UK and in Germany
Darmstadt, Germany, August 25, 2017 – Merck, a leading science and technology company, today announced that the European Commission (EC) has granted marketing authorisation for MAVENCLAD® 10mg (Cladribine Tablets) for the treatment of highly active relapsing multiple sclerosis∗ (RMS)1 in the 28 countries of the European Union (EU) in addition to Norway, Liechtenstein and Iceland. MAVENCLAD® is the first oral short-course treatment to provide efficacy across key measures of disease activity in patients with highly active RMS, including disability progression, annualized relapse rate and magnetic resonance imaging (MRI) activity.
“Multiple Sclerosis (MS) is one of the world’s most common neurological disorders. With the approval of MAVENCLAD® in the European Union, we are pleased to offer patients and clinicians an innovative agent with a simplified dosing schedule as a new approach to managing active relapsing MS,” said Belén Garijo, CEO Healthcare and Member of the Executive Board of Merck. ”This is a pivotal change in the treatment of MS which further demonstrates our unwavering commitment to advancing patient care.”
MAVENCLAD®’s marketing authoriSation is based on more than 10,000 patient years of data with over 2,700 patients included in the clinical trial program,2 and up to 10 years of observation in some patients. The clinical development program included data from three Phase III trials, CLARITY,3,4 CLARITY EXTENSION5 and ORACLE MS,6 the Phase II ONWARD study;7 and long-term follow-up data from the 8-year prospective registry, PREMIERE.8 The efficacy and safety results of these studies allowed for a full characterisation of the benefit-to-risk profile of MAVENCLAD®.
“This is an exciting moment and one that will change the way we treat MS. MAVENCLAD® is a selective immune reconstitution therapy (SIRT) which simplifies treatment administration, by giving patients just two short annual courses of tablets in four years. Patients can benefit from the treatment over a longer period of time without having to continually take medication and without the need for frequent monitoring.”
Gavin Giovannoni, Professor of Neurology at Barts and The London School of Medicine and Dentistry, Queen Mary University of London.
The authorisation follows a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) that was received in June 2017. MAVENCLAD® is expected to become commercially available to patients in Europe by prescription within the coming months, with initial launches in Germany and UK expected as early as September 2017. In addition, Merck plans additional filings for regulatory approval in other countries, including the United States.
“Multiple Sclerosis affects more than 700,000 people across Europe and has no cure to date,” said Anne Winslow, President of the European Multiple Sclerosis Platform. ”New treatment options will significantly help improve the quality of life of people living with active relapsing MS.”
In patients with high disease activity, post hoc analyses of the two-year Phase III CLARITY trial4,4 demonstrated that MAVENCLAD® reduced the annualized relapse rate by 67% and the risk of 6-month confirmed EDSS progression by 82% versus placebo. As demonstrated in the Phase III CLARITY EXTENSION5 study, no further MAVENCLAD® treatment was required in Years 3 and 4. The comprehensive dataset has informed the posology and monitoring requirements. The most clinically relevant adverse reactions were lymphopenia and herpes zoster. Lymphocyte counts must be assessed before, and during, treatment with MAVENCLAD®. MAVENCLAD® is contraindicated in certain groups including immunocompromised patients and pregnant women.
∗ Defined as: patients with 1 relapse during the previous year and ≥ 1 T1 Gd+ lesion or ≥ 9 T2 lesions while on therapy with other DMDs; OR patients with ≥ 2 or more relapses in the previous year, whether on DMD treatment or not.
1 MAVENCLAD® Summary of Product Characteristics August 2017
2 Merck data on file
3 Giovannoni G, Comi G, Cook S et al. A Placebo-Controlled Trial of Oral Cladribine for Relapsing Multiple Sclerosis. 2010 New England Journal of Medicine 362:416-426
4 Giovannoni G et al. Sustained disease-activity-free status in patients with relapsing-remitting multiple sclerosis treated with cladribine tablets in the CLARITY study: a post-hoc and subgroup analysis Lancet Neurol 2011; 10:329–337
5 EU Clinical Trials Register. A Phase IIIb, Double-Blind, Placebo-Controlled, Multicenter, Parallel Group, Extension Trial to Evaluate the Safety and Tolerability of Oral Cladribine in Subjects with Relapsing- Remitting Multiple Sclerosis Who Have Completed Trial 25643 (CLARITY). Available at https://www.clinicaltrialsregister.eu/ctr-search/trial/2007-000381-20/results. Last accessed August 2017
6 Leist T, Comi G, Cree B et al. Effect of oral cladribine on time to conversion to clinically definite multiple sclerosis in patients with a first demyelinating event (ORACLE MS): a phase 3 randomised trial. Lancet Neurol 2014; 13: 257–67
7 EU Clinical Trials Register. A phase II, multicenter, randomized, double-blind, placebo-controlled, safety, tolerability and efficacy study of add-on Cladribine tablet therapy with Rebif New Formulation in Multiple Sclerosis Subjects with Active Disease. Available at https://www.clinicaltrialsregister.eu/ctr- search/trial/2006-003366-33/results. Last accessed August 2017
8 Schreiner T, Miravalle A,. Current and Emerging Therapies for the Treatment of Multiple Sclerosis: Focus on Cladribine. Journal of Central Nervous System Disease. 2012; 4: 1–14
July saw the publication of a new NICE guideline for Parkinson’s in adults. The updated guideline NG71 replaces its 2016 predecessor guideline CG35 with new recommendations on treating Parkinson’s disease symptoms, deep brain stimulation, monitoring and managing impulse control disorders, and palliative care.
Central to a good Parkinson’s service is ensuring that all patients received joined-up care. Good communication between clinicians at every point along a patient’s journey is essential, and this includes ensuring that clinicians are confident when it comes to prescribing of and/or referral for the non-oral therapies.
The non-oral therapies for Parkinson’s include: apomorphine, intestinal levodopa gel infusion (Duodopa) and deep brain stimulation. For the right patients, these treatments can be truly life changing.
Most people with Parkinson’s will not need non-oral therapy – for many, tablet and patch medications will manage their symptoms very well. Furthermore, not everyone who is struggling on tablet medications will benefit from non-oral treatments and, of those who try them, not all will tolerate them.
However, for those patients who find their oral treatments are not working well, it’s useful to have the opportunity to have a discussion with a specialist about whether these treatments might have a role.
Last year a best practice pathway for the use of non-oral treatments in Parkinson’s was published, which was devised by clinicians to make the referral process for these therapies more explicit. The tool is an important resource to help clinicians understand the referral criteria and the local process for referral.
Dr Neil Archibald, Consultant Neurologist at James Cook University Hospital, Middlesbrough, Excellence Network Regional Lead for North East and Cumbria and steering group member who helped develop the pathway, said:
“The publication of a detailed pathway for the use of non-oral therapies in Parkinson’s is overdue and incredibly helpful. For too long we’ve been using, or trying to use, these treatments in a rather haphazard fashion. Some patients, in some parts of the country seem to get access and some doctors, in some parts of the country, seem to be unaware of them! What we really need is a “best practice” tool to help inform the management of some of the more complex symptoms of Parkinson’s and now we have one.”
Since the publication of the pathway Parkinson’s Academy has established a regional roadshow on the non-oral therapies. The one-day course called “Making the Most – Non-Oral Therapies in Parkinson’s” is designed to offer practical training to clinicians involved in Parkinson’s care and gives a road-map for the use of non-oral therapies.
The course covers:
What non-oral therapies are and how they work
What to expect when you make a referral
How to use data to convince commissioners
Case histories exploring how to use non-oral therapies.
Following the course’s popularity in 2016 and with the publication of the new NICE guideline for Parkinson’s, Parkinson’s Academy is holding an updated 2017 series of regional roadshows which explore the non-oral therapy pathway in detail. The course will address the implications of the 2017 NICE guidelines.
The roadshow dates planned for this year are:
Southampton, 16 October 2017
Manchester, 20 October 2017
Bristol, 6 November 2017
Edinburgh, 4 December 2017
To apply for your place, and to access the non-oral therapy pathway, simply visit the Parkinson’s Academy website:
This report explores the attitudes of both people with MS and their healthcare professionals towards treatment of the disease in the UK. The report is developed and funded by Sanofi Genzyme.
“MS is an unpredictable, progressive neurological condition. Therefore, there is no universal patient journey in MS; the severity and range of symptoms differ from one person to the next. Being able to access specialist care, including a multidisciplinary team and the right treatment as early as possible in the disease progression is vital. This new report is aligned with the nine consensus statements in the MS Trust’s MS Forward View report which sets out the ambition for the future of MS Services in England. Working together to raise public awareness and address areas where we lag behind is critical in order to transform care for and improve the quality of life of people who are affected by this complex condition.
The MS Trust is making great progress in addressing some of the issues in capacity through two key initiatives, the Specialist Nurse Programme and Advanced MS Champions Programme. We are delighted the wider community which engaged in the MS Forward View project is committed to achieving real change for people with MS.”
OCREVUS increased the number of patients with relapsing MS (RMS) and primary progressive MS (PPMS) who maintained No Evidence of Progression or Active Disease (NEPAD) versus Rebif (interferon beta-1a) in RMS and placebo in PPMS
OCREVUS significantly reduced the risk of RMS and PPMS patients requiring mobility aids versus comparators
In PPMS patients, OCREVUS reduced the risk of more severe forms of disability progression versus placebo
New post-hoc analyses from the OCREVUS® (ocrelizumab) Phase III clinical trial programme in people with relapsing and primary progressive forms of multiple sclerosis (RMS and PPMS) were presented at the 3rd Congress of the European Academy of Neurology (EAN) in Amsterdam.
OCREVUS significantly reduced disease activity and disability progression in patients with RMS and PPMS, as measured by No Evidence of Progression or Active Disease (NEPAD), a novel composite endpoint in MS. In RMS, OCREVUS significantly increased the proportion of patients maintaining NEPAD by 82 percent compared with Rebif® (interferon beta-1a) at 96 weeks in a pooled exploratory analysis of the Phase III OPERA I and II studies (p<0.001). In PPMS patients, OCREVUS more than tripled the proportion of those who maintained NEPAD compared with placebo at 120 weeks in an exploratory analysis of the Phase III ORATORIO study (29.9 percent with OCREVUS versus 9.4 percent with placebo, p<0.001).
NEPAD is considered a clinically meaningful endpoint because it signifies a patient has no relapses, no confirmed disability progression measured by the Expanded Disability Status Scale (EDSS), no progression equal to or above 20 percent on the timed 25-foot walk (T25-FW) and the nine-hole peg test (9-HPT), no gadolinium-enhancing T1 MRI lesions and no new or enlarging T2 MRI lesions.
“These results underline that the significant effects of OCREVUS on disability progression are clinically meaningful,” said Ludwig Kappos, MD, Chair of the Department of Neurology, University Hospital, Basel, Switzerland. “Slowing disability progression, or preventing people with MS from having to use a cane or wheelchair, makes a great difference to their daily lives. It is particularly exciting to see these benefits in people with PPMS, a disabling form of MS without approved treatments in Europe.”
In separate post-hoc analyses of the OPERA I and II studies, OCREVUS significantly reduced the risk of patients with RMS losing the ability to walk long distances unassisted (EDSS ≥4) or requiring a cane or crutch (EDSS ≥6) compared with interferon beta-1a at 96 weeks (p≤0.005). In the ORATORIO study, OCREVUS significantly reduced the risk of becoming wheelchair-bound (EDSS ≥7) compared with placebo at 120 weeks in PPMS patients with baseline EDSS ≤6 (p≤0.028).
Furthermore, in a post-hoc analysis of the placebo-controlled ORATORIO study, OCREVUS consistently reduced the risk of 12- and 24-week confirmed disability progression (CDP) across three different definitions of the measure meant to capture more severe disability worsening than traditionally assessed in PPMS patients.
In addition, interim results from FLOODLIGHT, a sensor-based digital monitoring study to determine adherence and correlation with in-clinic testing in people with and without MS, were presented. Pregnancy outcomes in all female patients treated with OCREVUS were also presented.
The most common side effects associated with OCREVUS in all Phase III studies were infusion reactions and upper respiratory tract infections, which were mostly mild to moderate in severity.
Leading investigators presented the following oral and poster presentations:
In parallel to EAN, Roche hosted a live MS Forum: ‘Shifting mind sets in Multiple Sclerosis – the need for policy change and better outcomes across Europe.’
OCREVUS is approved for use in the U.S. The OCREVUS Marketing Authorisation Application (MAA) has been validated by the European Medicines Agency (EMA) and is currently under review.
About the OPERA I and OPERA II studies in relapsing forms of MS
OPERA I and OPERA II are Phase III, randomised, double-blind, double-dummy, global multi-centre studies evaluating the efficacy and safety of OCREVUS (600 mg administered by intravenous infusion every six months) compared with interferon beta-1a (44 mcg administered by subcutaneous injection three times per week) in 1,656 people with relapsing forms of MS. In these studies, relapsing MS (RMS) was defined as relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) with relapses. A similar proportion of patients in the OCREVUS group experienced serious adverse events and serious infections compared with patients in the high-dose interferon beta-1a group in the RMS studies.
About the ORATORIO study in primary progressive MS
ORATORIO is a Phase III, randomised, double-blind, global multi-centre study evaluating the efficacy and safety of OCREVUS (600 mg administered by intravenous infusion every six months; given as two 300 mg infusions two weeks apart) compared with placebo in 732 people with primary progressive MS (PPMS). The blinded treatment period of the ORATORIO study continued until all patients had received at least 120 weeks of either OCREVUS or placebo and a predefined number of confirmed disability progression (CDP) events was reached overall in the study. A similar proportion of patients in the OCREVUS group experienced adverse events and serious adverse events compared with patients in the placebo group in the PPMS study.
About OCREVUS™ (ocrelizumab)
OCREVUS is a humanised monoclonal antibody designed to target CD20-positive B cells, a specific type of immune cell thought to be a key contributor to myelin (nerve cell insulation and support) and axonal (nerve cell) damage. This nerve cell damage can lead to disability in people with multiple sclerosis (MS). Based on preclinical studies, OCREVUS binds to CD20 cell surface proteins expressed on certain B cells, but not on stem cells or plasma cells, and therefore important functions of the immune system may be preserved.
OCREVUS is administered by intravenous infusion every six months. The initial dose is given as two 300 mg infusions given two weeks apart. Subsequent doses are given as single 600 mg infusions.
Ziemssen T. (2005). Modulating processes within the central nervous system is central to therapeutic control of multiple sclerosis. J Neurol, 252(Suppl 5), v38-v45.
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Data suggest that MAVENCLAD™ (Cladribine Tablets) selectively and discontinuously reduces B and T lymphocytes, with lymphocyte counts returning to normal range before the end of Year 2
The lymphocyte data presented at EAN Congress are consistent with other clinical safety presentations of MAVENCLAD™ (Cladribine Tablets) at the congress
Merck announced the presentation of safety and efficacy data on MAVENCLAD™ (Cladribine Tablets) for the treatment of relapsing MS at the 3rd Congress of the European Association of Neurology (EAN), in Amsterdam, the Netherlands.
Data from the placebo-controlled CLARITY, CLARITY Extension and ORACLE-MS clinical trials support the benefit:risk profile of Cladribine Tablets that have prompted an application for marketing authorisation in the EU, and the recent positive opinion from the Committee for Medicinal Products for Human Use (CHMP).
In these studies, Cladribine Tablets was administered as two annual treatment courses in Years 1 and 2, with a total maximum of 20 days of oral treatment equal to a dose of 3.5 mg/kg body weight, followed by no further active treatment in Years 3 and 4.
“These data presented at EAN Congress 2017 bring the MS treating community closer to understanding the mechanism of action of Cladribine Tablets,” said Professor Per Soelberg Sørensen, presenting author and Head of MS Research Unit, Danish Multiple Sclerosis Centre. “These data support the emerging theories around the ability of some agents to selectively ‘reset’ the immune system without the secondary autoimmunity that we sometimes see with treatments for relapsing MS. This would represent a significant advance in the field.”
About MAVENCLAD™ (Cladribine Tablets)
Cladribine Tablets is a short-course oral therapy that is believed to selectively and periodically target lymphocytes thought to be integral to the pathological process of MS. Cladribine Tablets is currently under clinical investigation and not yet approved for the treatment for any use in the United States, Canada and Europe. On 23 June, the Committee for Medicinal Products for Human Use (CHMP) granted a positive opinion on the use of Cladribine Tablets for highly active relapsing MS, and this recommendation has been passed on to the EC to make the final decision on the Marketing Authorization Application (MAA) later this year.
The clinical development program for Cladribine Tablets includes:
The CLARITY (CLAdRIbine Tablets Treating MS OrallY) study: a two-year Phase III placebo-controlled study designed to evaluate the efficacy and safety of MAVENCLAD as a monotherapy in patients with RRMS.
The CLARITY extension study: a four-year Phase III placebo-controlled study following on from the CLARITY study, designed to evaluate the safety and efficacy of MAVENCLAD over an extended administration for four years.
CLARITY (CLAdRIbine Tablets Treating MS OrallY) study and its extension: a two-year Phase III placebo-controlled study designed to evaluate the efficacy and safety of Cladribine Tablets as a monotherapy in patients with RRMS and its two-year extension designed to provide data on the long-term safety and efficacy of extended administration of Cladribine Tablets for up to four years.
ORACLE MS (ORAl CLadribine in Early MS) study: a two-year Phase III placebo-controlled study designed to evaluate the efficacy and safety of Cladribine Tablets as a monotherapy in patients at risk of developing MS (patients who have experienced a first clinical event suggestive of MS).
ONWARD (Oral Cladribine Added ON To Interferon beta-1a in Patients with Active Relapsing Disease) study: a Phase II placebo-controlled study designed primarily to evaluate the safety and tolerability of adding Cladribine Tablets treatment to patients with relapsing forms of MS, who have experienced breakthrough disease while on established interferon-beta therapy.
PREMIERE (Prospective Observational Long-term Safety Registry of Multiple Sclerosis Patients Who Have Participated in Cladribine Clinical Studies) study: interim long-term follow-up data from the prospective registry, PREMIERE, to evaluate the safety and efficacy of Cladribine Tablets. The follow-up will consist of over 10,000 patient years of exposure in total, with follow-up in some patients exceeding eight years at completion.
Apomorphine infusion effective in Parkinson’s – Metabolic syndrome increases risk of cognitive disorders – Openness may play a protective role in the co-occurrence of migraine and depression – Europe’s neurologists exceptionally scientifically productive – Heavy smart phone use can damage arm nerves – Statins not associated with increased polyneuropathy risk.
Apomorphine infusion effective in treating motor fluctuations of Parkinson’s
Apomorphine subcutaneous infusion is an effective treatment for Parkinson patients whose motor fluctuations are poorly controlled by conventional therapies. This was shown by the large-scale TOLEDO study presented at the congress.
Metabolic syndrome increases risk of cognitive disorders
A study presented at the congress has shown that obesity alone is not a risk factor for cognitive disorders, but commonly associated co-morbidities such as diabetes, high blood pressure and metabolic disorders are. Dementia diseases in patients who suffer from diabetes are often treated inadequately, a new research paper reveals.
Openness may play a protective role in the co-occurrence of migraine and depression
People with depression and neuroticism are particularly susceptible to migraine. This was shown in a current Hungarian/UK study presented at the congress. Openness to new experiences, on the other hand, may reduce the risk of developing migraine in people with history of depression.
High “gross neurological product”: Europe’s neurologists exceptionally scientifically productive European neurology is a highly productive discipline both in terms of quantity and quality – with continuous growth over the years. This is the result of an analysis of scientific publication presented at the congress.
Heavy users of smart phones tap on the touchscreen of their mobile phones more than 5,000 times a day. A study presented at the congress shows that these finger acrobatics can put a major strain on the nerves of the hand and arm. If the worst come to the worst, heavy users can develop carpal tunnel syndrome.
Statins not associated with increased polyneuropathy risk, Danish study says
It was long debated whether cholesterol-lowering statins can be conducive to the occurrence of neuropathies. A study presented at the congress now issues an all-clear signal: Patients treated with statins were not at greater risk of developing polyneuropathy than others.
Epilepsy: innovative substances and interventions – Guillain-Barré syndrome: risk influenced by month of birth – New antibody helps migraine patients who overuse medication
Epilepsy: innovative substances and interventions fly in the face of therapy resistance Numerous new medicines now deliver effective help for epilepsy patients. However, up to a third of patients do not respond to the available therapies sufficiently, if at all. A group of new substances including cannabinoids and neurosteroids were presented at the congress as a possible answer in the search for suitable treatments for severe, therapy-resistant forms of epilepsy. Less invasive neurosurgery techniques and the use of radiotherapies also provide new therapeutic options. Full article –> link
Guillain-Barré syndrome: risk of developing disorder influenced by month of birth October babies are more likely to develop Guillain-Barré syndrome, while fewer sufferers are born in June. This was the conclusion drawn by a Serbian, Bosnian and Montenegrin study. Full article –> link
New antibody helps migraine patients who overuse medication A new human antibody may soon become available as a specific medication for preventing frequent migraine attacks. As confirmed by an international team of researchers at the congress, there is a way to reduce the number of days that patients with medication overuse suffer from migraine headaches, as well as the quantity of medication for the treatment of acute migraine attacks they take. Full article –> link
Sunday June 25th
Outcomes measurements ever more important – Autoantibodies: new treatment options and challenges – Palliative neurology: early start, multidisciplinary approach – Hypertension associated with more serious forms of Parkinson’s.
Neurology congress in Amsterdam: Outcomes measurements are becoming ever more important How effective is a treatment, does it lead to the expected improvement and how can all this be measured in an objective manner? Outcomes measurements are increasingly important in neurology. Participants at the congress discussed latest development in the field of outcomes research and how patients benefit from these activities. Full article –> link
Autoantibodies: new treatment options and challenges in neurology Autoantibodies are increasingly being identified as the cause of nervous-system diseases. At the congress, Prof Angela Vincent spoke about the new treatment options emerging as a result and the degree to which screening makes sense, as well as the latest research findings. Full article –> link
Palliative neurology: early start, multidisciplinary approach Palliative medicine goes far beyond the treatment of people suffering from terminal cancer. It is precisely patients with incurable neurological diseases who can benefit enormously from early multidisciplinary palliative care. These views were expressed by experts at the congress. Full article –> link
Hypertension associated with more serious forms of Parkinson’s British and Italian scientists presented an important contribution to research on Parkinson’s disease. They managed to provide evidence that patients with hypertension are struck more seriously by Parkinson’s disease than patients with normal blood pressure. The hope is that optimum blood pressure management might help to mitigate the symptoms of Parkinson’s disease. Full article –> link
Saturday June 24th
Neurological diseases on the rise – Parkinson’s disease: early detection crucial – Cannabinoids suitable for migraine prevention – Sleep deprivation and disruption harm mind and body – Stroke research: almost three times as many patients could be disability-free.
Neurological diseases on the rise: European collaboration in research essential EU resources are the top source of funding for cross-border collaboration in neurological research. Prof Günther Deuschl, President of the European Academy of Neurology (EAN) expressed concern about tendencies toward Europe skepticism: “It is only together that we can handle the growing challenges in research.” More than 220 million people in Europe suffer from neurological diseases such as Alzheimer, dementia or headaches and that number is growing all the time. Full article –> link
Parkinson’s disease: early detection crucial, new therapy approaches on the horizon Detecting Parkinson’s disease before non-reversible symptoms occur: New approaches to early detection are meant to ensure just that. They are based on detection of alpha-synuclein in the skin or intestines. New therapy approaches such as a potential “vaccination” could improve the prognosis of affected individuals in future. Prof Günther Deuschl, President of the European Academy of Neurology (EAN), summarised the latest findings in research on Parkinson’s’ disease. Full article –> link
Cannabinoids suitable for migraine prevention A study confirmed that cannabinoids are just as suitable as a prophylaxis for migraine attacks as other pharmaceutical treatments. Interestingly though, when it comes to treating acute cluster headaches they are only effective in patients that suffered from migraine in childhood. Full article –> link
Sleep deprivation and disruption harm mind and body A chronic lack of sleep not only impairs cognitive abilities but also increases the risk of heart disease and diabetes. Current research discussed at the congress show that not only the amount of sleep is important but also whether it is taken at the right time. Full article –> link
Stroke research: almost three times as many patients could be disability-free in future Virtually no other disease has seen such massive strides in treatment in recent years as stroke. Recent studies have confirmed that it is still possible to mechanically remove large vessel occlusions in the brain many hours after a stroke occurs. Experts expressed optimism that the proportion of patients with lives free of serious disability after a major stroke could be increased by 270 percent. Full article –> link
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