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.

Tuesday June 27th

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.

Full article –> link

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. 

Full article –> link

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. 

Full article –> link

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.

Full article –> link

Heavy smart phone use can damage arm nerves

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.

Full article –> link

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. 

Full article –> link

Monday June 26th

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

Industry news:

Data Provide Insight into the Mode of Action of MAVENCLAD™ (Cladribine Tablets) in Patients with Relapsing MS

Roche’s OCREVUS (ocrelizumab) significantly reduced multiple measures of disease progression in relapsing and primary progressive multiple sclerosis

 Eslicarbazepine acetate was shown not to have a significant negative consequence on attention, information processing and working memory; ¹ in addition it was shown to be efficacious and generally well tolerated²

 Study 208 data presented at the 12th European Paediatric Neurology Society (EPNS) Congress in Lyon, France

22nd June: Bial and Eisai announced data from a Phase II study which showed that treatment with Zebinix® (eslicarbazepine acetate) had no significant negative impact on attention, information processing and working memory in children aged 6-16 years old with focal-onset epilepsy.¹ It is well-documented that some anti-epileptic drugs (AEDs) may contribute to negative effects on cognition in epilepsy, underscoring the importance of this clinically meaningful data.³

Data was presented 22nd June in an oral presentation at the EPNS Congress in Lyon, France.¹

Study 208 is a randomised Phase II trial evaluating the effect of adjunctive eslicarbazepine acetate (n=83) on Power of Attention in children aged 6-16 years old with refractory focal onset epilepsy versus placebo (n=40). Eslicarbazepine acetate also demonstrated no statistically significant difference for secondary endpoints including continuity of attention, quality of working memory and speed of memory at the end of Part I.¹

“Childhood and adolescence are critical times for learning and development,” explains Ann Connolly, Registered Advanced Nurse Practitioner Epilepsy (Childhood), National Children’s Hospital, Adelaide and Meath Hospital, Dublin, Ireland. “These findings may indicate that eslicarbazepine acetate has no significant negative consequence on the neurocognitive capability of children. This is important as the treatment may help support normal learning and schooling, which will stand these children in good stead for the future.”

For the overall age group there were no significant Power of Attention differences in Part I between eslicarbazepine acetate and placebo, with a Least Square mean difference of 33.2 milliseconds (95% CI: – 137.6, 204.0; p=0.700). Power of Attention was defined as the sum of the reaction time measures from the attentional tasks (simple reaction time [dominant hand only], choice reaction time and digit vigilance speed.¹ Overall incidence in study 208 of treatment emergent adverse events (TEAEs) was similar (45% for ESL and 48% for placebo).² The most frequently reported TEAEs with eslicarbazepine acetate treatment were headache, somnolence and vomiting.²

“A major treatment goal for neurologists managing childhood epilepsy is to achieve seizure freedom with minimal or no adverse effects, of which neurocognition is an important consideration. Few clinical trials have examined the cognitive effects of AEDs in childhood epilepsy so this new data is reassuring and supports the use of eslicarbazepine acetate in these difficult-to-treat patients,” commented Professor Stéphane Auvin, Professor of Epilepsy & Child Neurology at the Université Denis Diderot, member of the Paediatric Commission of ILAE and board member of the French Paediatric Neurology Society Paris, France.

Approximately 10.5m children and adolescents worldwide are estimated to have active epilepsy.⁴ Children with epilepsy may suffer from cognitive impairment and have impaired ability to learn.⁵ Epilepsy may have a significant impact on a child’s quality of life, academic achievement and psychosocial outcomes in later life.^{6, 7}

Eslicarbazepine acetate is indicated in Europe as adjunctive therapy in adults, adolescents and children aged above 6 years, with partial-onset seizures with or without secondary generalisation.^[viii] Eslicarbazepine acetate is also indicated in Europe as a monotherapy in the treatment of partial-onset seizures, with or without secondary generalisation, in adults with newly diagnosed epilepsy.⁸

References

[i] Veggiotti P, et al. Effect of eslicarbazepine acetate on neurocognitive functions in children with epilepsy. Presented at EPNS 2017. Oral Presentation #OC58

[ii] Jóźwiak S, et al. Efficacy and tolerability of eslicarbazepine acetate in children with epilepsy: results from a phase II study. Presented at EPNS 2017. Oral Presentation #OC57

[iii] Mula M, et al. Antiepileptic Drug-Induced Cognitive Adverse Effects. CNS Drugs 2009;23:121-137

[iv] Guerrini R, Epilepsy in Children, The Lancet 2006; 9505:499-524.

[v] Melbourne Chambers R, et al. Cognition, academic achievement and epilepsy. Epilepsy & Behavior 2014; 39-44

[vi] Mitchell WG, et al. Academic underachievement in children with epilepsy. Journal of Child Neurology 1991;6:65–72.

[vii] Carpay HA, et al. Disability due to restrictions in childhood epilepsy. Developments in Medicine & Child Neurology 1997;39:521–6.

[viii] Zebinix^® (eslicarbazepine acetate) Summary of Product Characteristics. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000988/WC500047225.pdf Accessed June 2017.

[ix]Epilepsy in the WHO European Region: Fostering Epilepsy Care in Europe. Available at: http://www.ibe-epilepsy.org/downloads/EURO%20Report%20160510.pdf Accessed June 2017

[x] Hebeisen S, et al. Eslicarbazepine and the enhancement of slow inactivation of voltage-gated sodium channels: a comparison with carbamazepine, oxcarbazepine and lacosamide. Neuropharmacology 2015; 89:122-35

[xi] Elger C, et al. Eslicarbazepine acetate: A double-blind, add-on, placebo-controlled exploratory trial in adult patients with partial-onset seizures. Epilepsia 2007; 48:497-504

[xii]Elger C, et al. 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 2009;50:454-63

[xiii]Ben-Menachem E, et al. Eslicarbazepine acetate as adjunctive therapy in adult patients with partial epilepsy. Epilepsy Research 2010;89(2-3):278-85

[xiv]Gil-Nagel A, et al. Efficacy and safety of 800 and 1200 mg eslicarbazepine acetate as adjunctive treatment in  adults with refractory partial-onset seizures. Acta Neurologica Scandinavica 2009; 120:281-87

European Commission grants Marketing Authorisation for Zebinix® (eslicarbazepine acetate) as once-daily monotherapy in adults with newly diagnosed partial-onset epilepsy 

Bial and Eisai announced on 23rd May that the European Medicines Agency (EMA) has approved Zebinix® (eslicarbazepine acetate) for use as a once-daily monotherapy to treat adults with newly-diagnosed partial-onset epilepsy. Zebinix® is already indicated in Europe as adjunctive therapy in adults, adolescents and children aged above 6 years, with partial-onset seizures with or without secondary generalisation.¹

This marketing authorisation is based on results from a Phase III, randomised, double-blind, active-controlled, non-inferiority study (Study 311) which compared once-daily eslicarbazepine acetate as monotherapy to twice-daily, controlled-release carbamazepine in newly diagnosed adults with partial-onset seizures. The primary endpoint was the proportion of patients seizure-free for the entire 26-week evaluation period.² The data show that 71.1% (n=276/388) of patients for eslicarbazepine acetate and 75.6% (n=300/397) of patients for controlled-release carbamazepine were seizure-free for six months or more, at the last evaluated dose (average risk difference -4.28%; 95% CI -10.3, 1.74%). The one-year seizure-freedom rate at the last evaluated dose was 64.7% (n=251/388) on eslicarbazepine acetate and 70.3% (n=279/397) on controlled-release carbamazepine (average risk difference: -5.46%; 95% CI: -11.88, 0.97%).²

“Epilepsy is a chronic disorder of the brain and one of the most common neurological conditions worldwide,” said Eugen Trinka, Professor and Chair of Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University, Salzburg, Austria. “This approval brings the promise of a new monotherapy option for over half of patients with epilepsy who experience partial-onset seizures.”

Eslicarbazepine acetate has an innovative mode of action that is different from other sodium channel blockers.^1,3 It selectively targets the slow inactivated state of the sodium ion channel (which has been implicated in the pathogenesis of epilepsy), preventing its return to the active state,³ and thereby reduces repetitive neuronal firing, based on animal data.³ The recommended starting dose is 400 mg once daily which should be increased to 800 mg once daily after one or two weeks. Based on individual response, the dose may be increased to 1,200 mg once daily. Some patients on a monotherapy regiment may benefit from a dose of 1,600 mg once daily.¹

“We are pleased that adults with partial-onset epilepsy across Europe are now able to benefit from a once-daily monotherapy option that is simple to use, which may optimise their adherence,” comments António Portela, CEO of Bial, Porto, Portugal. “Bial has an ongoing commitment to all people living with epilepsy and we look forward to continuing to work with the epilepsy community to bring this new indication to patients.”

“This decision for eslicarbazepine acetate by the European Commission reinforces Eisai’s commitment to researching and developing neurological treatment options that have the potential to help people manage epilepsy more effectively. This milestone means that newly-diagnosed adult patients in Europe who experience partial-onset epilepsy will now have a broader range of treatment options available,” comments Neil West, Vice President EMEA, Global Neurology Business Unit at Eisai.

A safety analysis of the Phase III study showed that the tolerability profile of eslicarbazepine acetate was similar to that of twice-daily controlled-release carbamazepine.⁴ The side effects of eslicarbazepine acetate were mostly of mild intensity, and consistent with the known safety profile.

Incidence rates of treatment-emergent adverse events (TEAEs) were similar but slightly higher in patients receiving controlled-release carbamazepine (77.7%) (n=320/412) versus eslicarbazepine acetate (75.3%) (n=302/401). Possibly-related TEAEs were also slightly higher at 49.5% (n=204/412) for controlled-release carbamazepine compared with 41.1% (n=165/401) for eslicarbazepine acetate, for serious possibly-related TEAEs (2.7% vs 2.0%) (n=11/412 vs n=8/401), and for TEAEs leading to withdrawal (18.0% vs 13.5%) (n=74/412 vs n=54/401). The most frequently reported possibly-related TEAEs for eslicarbazepine acetate were, in order of most frequent, dizziness, headache, somnolence, fatigue and nausea.⁴

References

1 Zebinix® (eslicarbazepine acetate) Summary of Product Characteristics. Available at: http://www.medicines.org.uk/emc/medicine/22376 Accessed May 2017.

2 Ben-Menachem E, et al. Efficacy of eslicarbazepine acetate versus controlled-release carbamazepine as monotherapy in patients with newly diagnosed partial-onset seizures; European Congress on Epileptology 2016: Abstract #0002

3 Hebeisen S, et al. Eslicarbazepine and the enhancement of slow inactivation of voltage-gated sodium channels: a comparison with carbamazepine, oxcarbazepine and lacosamide. Neuropharmacology 2015; 89:122-35

4 Kowacs P, et al. Safety and tolerability of eslicarbazepine acetate as monotherapy in patients with newly diagnosed partial-onset seizures. Presented at EAN 2016; abstract #P32045

5 Elger C, et al. Eslicarbazepine acetate: A double-blind, add-on, placebo-controlled exploratory trial in adult patients with partial-onset seizures. Epilepsia 2007; 48:497-504

6 Elger C, et al. 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. 2009;50:454-63

7 Ben-Menachem E, et al. Eslicarbazepine acetate as adjunctive therapy in adult patients with partial epilepsy. Epilepsy Res. 2010;89(2-3):278-85

8 Gil-Nagel A, et al. Efficacy and safety of 800 and 1200 mg eslicarbazepine acetate as adjunctive treatment in adults with refractory partial-onset seizures. Acta Neurol Scand. 2009; 120:281-87

9 Epilepsy in the WHO European Region: Fostering Epilepsy Care in Europe. Available at: http://www.ibe-epilepsy.org/downloads/EURO%20Report%20160510.pdf Accessed March 2017

11th April 2017 was World Parkinson’s Day and the anniversary of James Parkinson’s birth. It was also 200 years since he published his essay on the shaking palsy.

Watch our film about world authority on PD Professor Andrew Lees, by award winning documentary maker Ben Crowe, in which Professor Lees calls for a more creative approach to research.

Watch the video here

Funding for the production of this film was provided by Profile Pharma. Profile Pharma had no input into or influence over the content of the film.

Teva Pharmaceutical Industries Ltd have announced that the label for COPAXONE® (glatiramer acetate) injection 20mg/mL, used for treatment in patients with relapsing forms of multiple sclerosis (RMS), has been updated in the UK to remove the pregnancy contraindication.

The label update followed an extensive analysis by regulatory authorities of available pregnancy cases among women who were already taking COPAXONE® when they learned they were pregnant. A supporting analysis was also provided comparing data from Teva’s Glatiramer Acetate (GA) Pharmacovigilance Database which captured more than 8,000 pregnancies over a period of more than 20 years.

Staying on an MS treatment like COPAXONE® 20 mg/mL is now an option women can discuss with their doctor because COPAXONE® is no longer contraindicated during pregnancy.

As a precautionary measure, it is preferable to avoid the use of COPAXONE® during pregnancy unless the benefit to the mother outweighs the risk to the foetus.

Professor Gavin Giovannoni, Chair of Neurology – Blizard Institute, Barts and The London, said, “People with multiple sclerosis want to live normal lives, but, for many women with relapsing MS, having to decide between planning a family and staying on their treatment to manage relapses is a reality they have to face. This label update provides specialists and their patients with MS, who are considering starting or extending their family, an important option in relation to their treatment of MS during pregnancy.”

For more information, visit www.tevapharm.com

Published online: 14/3/17

The European Commission (EC) has extended the Marketing Authorisation for Zebinix® (eslicarbazepine acetate) as a once-daily adjunctive treatment for patients aged above six years with partial-onset (focal) seizures with or without secondary generalisation.[i]

Eslicarbazepine acetate was previously indicated only for the adjunctive treatment of adults aged over 18 with partial-onset seizures with or without secondary generalisation.[ii]

The variation to the license is based on data from one Phase III study (305), one Phase II study (208) and from population PK modelling and exposure-efficacy analyses. The Commission considered the efficacy results from the mentioned studies to be acceptable for an extension of the Marketing Authorisation. The safety analyses show no new or unexpected safety ndings and eslicarbazepine acetate does not appear to have negative neurocognitive consequences (power of attention, information processing and working memory).[iii]

References

[i] European Commission: Community register of medicinal products for human use. Product Information – Zebinix. Available at: http://ec.europa.eu/health/documents/community- register/html/h514.htm Last updated December 2016
[ii] Zebinix SMPC, Available at http://www.ema.europa.eu/docs/en_GB/document_library/ EPAR_-_Product_Information/human/000988/WC500047225.pdf Last updated: May 2016
[iii] Moreira J, et al. J Neurol Sci 2015;357:e432–456 (abstract 1513; WFN15-1735; e439)

Published online: 14/3/17