Author: Rachael Hansford

US approval for ULTOMIRIS® for gMG

ULTOMIRIS® (ravulizumab-cwvz) approved in the US for Adults with Generalised Myasthenia Gravis

First and only long-acting C5 complement inhibitor to demonstrate clinical improvement in patients with generalised myasthenia gravis

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

April 28, 2022: ULTOMIRIS®(ravulizumab-cwvz) has been approved in the US for the treatment of adult patients with generalised myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody-positive, which represents 80% of people living with the disease.1-5

The approval by the Food and Drug Administration (FDA) was based on positive results from the CHAMPION-MG Phase III trial, in which ULTOMIRIS was superior to placebo in the primary endpoint of change from baseline in the Myasthenia Gravis-Activities of Daily Living Profile (MG-ADL) total score at Week 26, a patient-reported scale that assesses patients’ abilities to perform daily activities.1

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

gMG is a rare, debilitating, chronic, autoimmune neuromuscular disease that leads to a loss of muscle function and severe weakness.6 The diagnosed prevalence of gMG in the US is estimated at approximately 90,000.7

Despite recent advances, managing gMG is complex. Earlier intervention can preserve function and quality of life. This approval offers patients, including those with milder symptoms, a long-acting C5 inhibitor with early onset and reliable efficacy.

Professor James F. Howard, Jr, MD, Department of Neurology at The University of North Carolina School of Medicine and lead primary investigator in the CHAMPION-MG trial.

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

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

In the trial, the safety profile of ULTOMIRISwas comparable to placebo and consistent with that observed in Phase III trials of ULTOMIRIS in paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS). The most common adverse reactions in patients receiving ULTOMIRIS were upper respiratory tract infection and diarrhea.1

Results from the CHAMPION-MG trial were recently published online in NEJM Evidence and presented at the 2022 American Academy of Neurology Annual Meeting in April.

Regulatory submissions for ULTOMIRISfor the treatment of gMG are currently under review with multiple health authorities, including in the European Union (EU) and Japan.


  1. Ultomiris (ravulizumab-cwvz) US prescribing information; 2022.
  2. Anil, R., Kumar, A., Alaparthi, S., Sharma, A., Nye, JL., Roy, B., O’Connor, KC., Nowak, R., (2020). Exploring outcomes and characteristics of myasthenia gravis: Rationale, aims and design of registry – The EXPLORE-MG registry. J Neurol Sci. 2020 Jul 15;414:116830.
  3. Oh SJ., (2009). Muscle-specific receptor tyrosine kinase antibody positive myasthenia gravis current status. Journal of Clinical Neurology. 2009b Jun 1;5(2):53-64.
  4. Tomschik, M., Hilger, E., Rath, J., Mayer, EM., Fahrner, M., Cetin, H., Löscher, W., Zimprich, F., (2020). Subgroup stratification and outcome in recently diagnosed generalized myasthenia gravis. Neurology. 2020 Sep 8;95(10):e1426-e1436.
  5. Hendricks, TM., Bhatti, MT., Hodge, D., Chen, J., (2019). Incidence, Epidemiology, and Transformation of Ocular Myasthenia Gravis: A Population-Based Study. Am J Ophthalmol. 2019 Sep;205:99-105.
  6. Howard, J. F., (2017). Myasthenia gravis: the role of complement at the neuromuscular junction. Annals of The New York Academy of Sciences, 1412(1), 113-128.
  7. Westerberg, E., Punga, A., (2020). Epidemiology of Myasthenia Gravis in Sweden 2006–2016. Brain and behavior. 2020 Nov;10(11):e01819.
  8. Myasthenia Gravis. National Organization for Rare Disorders (NORD). Available here. Accessed March 2022.
  9. Howard, J. F., (2015). Clinical Overview of MG. Available here. Accessed March 2022.
  10. Sanders, D. B., Raja, S. M., Guptill J. T., Hobson-Webb, L. D., Juel, V. C., & Massey, J. M., (2020). The Duke myasthenia gravis clinic registry: I. Description and demographics. Muscle & Nerve, 63(2), 209-216.
  11. Myasthenia Gravis Fact Sheet. (2020, April 27). National Institutes of Neurological Disorders and Stroke. Available here. Accessed March 2022.
  12. Ding, J., Zhao, S., Ren, K., Dang, D., Li, H., Wu, F., Zhang, M., Li, Z., & Guo, J., (2020). Prediction of generalization of ocular myasthenia gravis under immunosuppressive therapy in Northwest China. BMC Neurology, 20(238).
  13. Safety and Efficacy Study of Ravulizumab in Adults With Generalized Myasthenia Gravis. NCT Identifier: NCT03920293. Available here. Accessed March 2022.

Biogen withdraws marketing authorisation application for aducanumab for Alzheimer’s disease

  • Biogen has informed the European Medicines Agency (EMA) that it is withdrawing its application for marketing authorisation for aducanumab for the treatement of Alzheimer’s disease
  • The EMA had previously found on 16 December 2021 that the benefits of aducanumab did not outweigh its risks and recommended refusing marketing authorisation. Biogen then requested a re-examination.
  • Following Biogen’s discussions with the EMA’s Committee for Medicinal Products for Human Use (CHMP), in which the CHMP indicated that the “data provided thus far would not be sufficient to support a positive opinion”, the company has decided to withdraw the application.
  • It has been 20 years since the last approval of an Alzheimer’s medicine by the EMA.
  • Biogen is set to launch a phase IV trial of aducanumab in May 2022.

On 22 April 2022 Biogen announced that it had notified the European Medicines Agency (EMA) about the withdrawal of its marketing authorisation application for aducanumab for the treatment of early Alzheimer’s disease.

The agency had previously found on 16 December 2021 that the benefits of aducanumab did not outweigh its risks and had therefore recommended refusing marketing authorisation. Biogen requested a re-examination of the EMA’s decision and started discussions with the Agency’s Committee for Medicinal Products for Human Use (CHMP). In its press release issued today, Biogen highlighted that the CHMP had indicated that the “data provided thus far would not be sufficient to support a positive opinion”.

With the last approval of an Alzheimer’s medicine by the EMA dating back to 2002, people living in Europe affected by Alzheimer’s disease have been waiting to gain access to better treatments for 20 years. It will therefore be disappointing news for them to hear that there was insufficient scientific evidence for the EMA to support the authorisation of aducanumab, and that the wait for innovative, disease modifying treatments will have to continue in Europe.

The EMA discussions and the decision by Biogen to withdraw its marketing authorisation application follow developments in the US where the Food and Drug Administration (FDA) chose to grant conditional approval for aducanumab using its “accelerated approval pathway”. This approval was based on aducanumab’s proven effect on lowering amyloid beta, a surrogate endpoint that the FDA deemed “reasonably likely” to predict a clinical benefit to patients.

In its December recommendation, the EMA recognised that aducanumab reduces amyloid beta in the brain, but stated that “the link between this effect and clinical improvement has not been established”. The agency found that the results on cognition and executive function derived from the two phase III clinical trials conducted to date were conflicting, and highlighted potential difficulties in monitoring side effects of the medicine in clinical practice. As a result, the agency concluded that the risk-benefit balance was unfavourable and decided against approval. According to the EMA, “At the time of the withdrawal, while the re-examination was ongoing, the Agency was still of the opinion that the benefits of [aducanmab] did not outweigh its risks.”

Manoj Sivan to deliver keynote lecture at AFRM conference

The Australasian Faculty of Rehabilitation Medicine has invited Dr Manoj Sivan to deliver the keynote lecture at its conference in Melbourne, Australia on 12 May, 2022. Dr Sivan one of only three UK rehabilitation specialists to have ever been invited to give this prestigious lecture.

The AFRM’s annual keynote lecture was named the George Burniston Oration as part of efforts to showcase its history and pay homage to its founders. Further information about the history of the Oration can be found on the RACP website.

ZTALMY® (ganaxolone) Phase 3 Marigold Trial Results

Marinus Pharmaceuticals Announces Publication in The Lancet Neurology of ZTALMY® (ganaxolone) Phase 3 Marigold Trial Results

Results demonstrate safety and efficacy of ZTALMY, first FDA-approved treatment for seizures associated with CDKL5 deficiency disorder in patients two years and older

Marinus Pharmaceuticals, Inc., a pharmaceutical company dedicated to the development of therapeutics to treat seizure disorders, announced on 15 April 2022 that The Lancet Neurology has published results from the pivotal Phase 3 Marigold trial of ZTALMY® (ganaxolone) for the treatment of seizures associated with CDKL5 deficiency disorder (CDD). The paper, “Efficacy and safety of ganaxolone in patients with CDKL5 deficiency disorder: a randomized, double-blind, placebo-controlled, Phase 3 trial,” can be accessed on The Lancet Neurology website. This was the first double-blind placebo-controlled study providing evidence of efficacy in CDD-associated seizures.

The publication of these data highlights the importance of bringing new treatments to people affected by very refractory epilepsy, including the CDKL5 deficiency disorder community, and adds to the growing body of clinical research data currently available. The results demonstrate that ZTALMY was effective in treating seizures associated with CDKL5 deficiency disorder and provides physicians with a novel medication for the management of this difficult to treat patient population.

Dr. Elia M. Pestana Knight, M.D., a Principal Investigator for the Marigold trial and pediatric epileptologist at the Cleveland Clinic Neurological Institute.

Dr. Pestana Knight is a member of Marinus’ Scientific Advisory Board. She joined the Board after the completion of the Marigold randomised trial.

The paper presents the results of the Phase 3 Marigold trial, a double-blind placebo-controlled trial in which 101 patients were randomised and individuals treated with ZTALMY showed a median 30.7% reduction in 28-day major motor seizure frequency, compared to a median 6.9% reduction for those receiving placebo, achieving the trial’s primary endpoint (p=0.0036). ZTALMY was generally well-tolerated and showed a safety profile consistent with previous clinical trials, with the most frequent adverse event being somnolence.

About CDKL5 Deficiency Disorder

CDKL5 deficiency disorder (CDD) is a serious and rare genetic disorder that is caused by a mutation of the cyclin‑dependent kinase‑like 5 (CDKL5) gene, located on the X chromosome. CDD is characterised by early‑onset, difficult‑to‑control seizures and severe neurodevelopmental impairment.

About ZTALMY® (ganaxolone) oral suspension

ZTALMY® is the first and only FDA-approved treatment indicated specifically for seizures associated with cyclin-dependent kinase-like 5 deficiency disorder (CDD) in patients two years of age and older. ZTALMY, a neuroactive steroid that acts as a positive allosteric modulator of the GABAA receptor, is taken three times daily. It is expected to be available in the US in July 2022 following scheduling by the US Drug Enforcement Administration.

Ganaxolone does not currently have a marketing authorisation in the UK for treating seizures caused by CDD. NICE began a Health Technology Appraisal in the UK in January 2022. Orion Corporation signed a European wide marketing and distribution agreement with Marinus Pharmaceuticals for ganaxolone in August 2021.

Indication and Usage

ZTALMY is indicated for the treatment of seizures associated with cyclin-dependent kinase like 5 (CDKL5) deficiency disorder (CDD) in patients 2 years of age and older.

About Marinus Pharmaceuticals

Marinus is a pharmaceutical company dedicated to the development of innovative therapeutics to treat seizure disorders. Ganaxolone is a neuroactive steroid GABAA receptor modulator that acts on a well-characterised target in the brain known to have anti-seizure effects. It is being developed in IV and oral dose formulations intended to maximise therapeutic reach to adult and pediatric patient populations in both acute and chronic care settings. For more information visit

Diroximel fumarate receives positive recommendation from NICE for oral treatment of relapsing-remitting multiple sclerosis (RRMS)

  • Diroximel fumarate is a next generation, at-home, oral fumarate treatment, with established efficacy and well-characterised safety, for people living with relapsing-remitting multiple sclerosis (RRMS)1,2
  • Phase 3 data and real-world evidence (n=263, based in the US) have demonstrated that treatment with diroximel fumarate results in low discontinuation rates due to its gastrointestinal (GI) tolerability profile3,7 
  • The recommendation strengthens Biogen’s established MS portfolio and ongoing commitment to introducing therapies that positively impact the lives of those living with MS 

Biogen UK announced on April 13 2022 that the National Institute for Health and Care Excellence (NICE) has published a positive Final Appraisal Document (FAD) recommending VUMERITY® (diroximel fumarate), an oral fumarate, for the treatment of adults living with active RRMS[*] in England, Wales and Northern Ireland. The medicine was fast tracked to FAD enabling all eligible patients to have access to diroximel fumarate as soon as possible, providing another important option when considering the right treatment for their individual needs.

Approximately 115,880 people are currently living with MS in England, Wales and Northern Ireland.It is estimated that 85% are living with RRMS, the most common form of the condition.Diroximel fumarate offers those living with RRMS a treatment option with an improved gastrointestinal (GI) tolerability profile and comparable efficacy and safety characteristics to established treatment dimethyl fumarate (due to bioequivalence).3-6  The new oral fumarate treatment can reduce the severity and frequency of burdensome GI events like nausea, vomiting, diarrhoea and upper and lower abdominal pain, whilst also offering the convenience and flexibility to be taken with or without food.2-6,10

“For some people, their current oral fumarate may cause them to experience stomach issues which can affect their daily activities and productivity. Diroximel fumarate successfully decreases the chances of relapses but also causes fewer gastrointestinal side effects, which is critical in supporting people to start and stay on treatment. Today’s fast-tracked approval of diroximel fumarate follows approval in Scotland, providing equitable access across the UK. These positive recommendations enable us to offer an alternative at-home, oral DMT while avoiding a potential switch to an injectable therapy.

Dr Martin Duddy, Consultant Neurologist, Royal Victoria Infirmary, Newcastle

“Effective treatments that fit into daily life can help people live a life with MS that is not defined by MS. People living with MS can be confident in the established efficacy of this new oral treatment that has fewer stomach problems to manage. This can mean that they don’t have to factor their medication in relation to mealtimes.” said David Martin, CEO, MS Trust.

NICE’s decision was based on data from pivotal phase 3 trials (EVOLVE-MS-1 and EVOLVE-MS-2), which compared diroximel fumarate and dimethyl fumarate and demonstrated similar efficacy safety profiles.4,5 GI events, such as nausea, vomiting, diarrhoea and upper and lower abdominal pain were less severe and lasted fewer days with diroximel fumarate compared with dimethyl fumarate and therefore were less likely to interfere with patients’ daily lives.5,6  In addition, since diroximel fumarate’s launch in the US, real-world evidence has reinforced the GI tolerability profile and confirmed that patient experience demonstrated in clinical trials is consistent with clinical practice. The real-world retrospective analysis of persistence[†] and adherence in DRF-treated patients (n=263) showed high overall persistence over 12 months (~81.8%) [95% CI, 76.1–86.3], low discontinuation rate due to GI AEs (4.6%, 12/263) and high adherence to therapy (mean PDC 89.7%),[‡] aligning with expectations based on DRF clinical trials.7

“Following the Scottish Medical Consortium approval, the recommendation of diroximel fumarate by NICE marks our third MS product launched in the last 12 months. This is a significant milestone in our ambition to advance treatment and improve outcomes for people living with RRMS,” said Dr Mihaela Vlaicu, Head of Medical Affairs, Biogen UK and Ireland. “For nearly 25 years, we have led in the research and development of new MS therapies, continually striving to help address the diverse needs that people living with MS may have throughout their lives.” 

NICE’s recommendation follows the Scottish Medicine Consortium’s acceptance earlier this year, and the Medicines and Healthcare products Regulatory Agency (MHRA) and European Union authorisation in December 2021. The NICE FAD represents finalisation of the NICE Committee recommendations and forms the basis of the final Technology Appraisal Guidance (TAG) which is expected to be published in May. Once a positive recommendation is made through the fast-track appraisal process, NHS England commissioners have committed to providing funding for the technologies within 30 days of guidance publication. 


1.     National Institute for Health and Care Excellence. Final appraisal document. Diroximel fumarate for treating relapsing remitting multiple sclerosis. April 2022.

2.     Electronic Medicines Consortium. Vumerity 231 mg gastro-resistant hard capsules. Available at: Accessed: March 2022.

3.     Palte MJ, et al. Adv Ther 2019;36(11):3154-3165.

4.     Wehr YA, et al. Presented at 2018 American Academy of Neurology Annual Meeting; 21–27 April, 2018; Los Angeles, USA. P403.

5.     Naismith RT, et al. Mult Scler 2020 26(13):1729-1739. 

6.     Naismith RT, et al. CNS Drugs 2020;34(2):185-196. 

7.     Larger et al. Multiple Sclerosis Patients Treated With Diroximel Fumarate Over 1 Year in the Real-world Setting Have High Rates of Persistence and Adherence. 37th Congress of the European Committee for Treatment & Research in Multiple Sclerosis. 2021, P838.

8.     MS Trust. Available at: Accessed March 2022.

9.     NICE. Multiple Sclerosis: How common is it? Available at:

10. MS Society. Relapsing Remitting MS. Available here: Accessed March 2022.

11. Diroximel fumarate. Patient Information Leaflet. DRF Patient Leaflet GB ( Accessed March 2022. 

12. Tecfidera Data on file #028. Post Marketing Exposure Experience. March 2021.

13. Electronic Medicines Consortium. Tecfidera 120mg and 240mg gastro-resistant hard capsules. Available at: Accessed March 2022.

14. Wray et al. Diroximel Fumarate in Patients With Relapsing-Remitting Multiple Sclerosis: Interim Safety and Efficacy Results From the Phase 3 EVOLVE-MS-1 Study, 37th Congress of the European Committee for Treatment & Research in Multiple Sclerosis. October 13-15, 2021, P739.

About diroximel fumarate
Diroximel fumarate is indicated for the treatment of adult patients with relapsing remitting multiple sclerosis. It is an oral fumarate with an improved chemical structure to dimethyl fumarate. Once in the body, diroximel fumarate rapidly converts to monomethyl fumarate, the same active metabolite of dimethyl fumarate providing similar efficacy and safety profiles.2

Diroximel fumarate is another treatment option for RRMS and has a safety and efficacy profile consistent with dimethyl fumarate, with lower rates of GI AEs.3-6

Common adverse events are (may affect up to 1 in 10 people); inflammation of the lining of the intestines (gastroenteritis), being sick (vomiting), indigestion (dyspepsia), inflammation of the lining of the stomach (gastritis), digestive system problems (gastrointestinal disorder), burning sensation, hot flush, feeling hot, itchy skin (pruritus), rash, pink or red blotches on the skin (erythema). Side effects which may show up in blood or urine tests; proteins (albumin) in urine (proteinuria), increase in levels of liver enzymes (ALT, AST) in the blood. Very common (may affect more than 1 in 10 people); reddening of the face or body feeling warm, hot, burning, or itchy (flushing), loose stools (diarrhoea), feeling sick (nausea), stomach pain or stomach cramps. Side effects which may show in blood or urine tests; ketones in urine; low levels of white blood cells (lymphopenia, leukopenia) in the blood.1,11

Diroximel fumarate was first approved by the U.S. Food and Drug Administration in October 2019. Since its launch in the U.S., real-world data have reinforced the GI tolerability profile and confirmed that the experience demonstrated in clinical trials is consistent with clinical practice.7 Diroximel fumarate is approved for use in adult with RRMS in US, Europe, and Israel.

About dimethyl fumarate
Dimethyl fumarate, a treatment for RRMS in adults, has been shown to reduce the rate of MS relapses, slow the progression of disability and impact the number of MS brain lesions, while demonstrating a well-characterised safety profile in people with relapsing forms of MS. More than 537,432 patients have been treated with dimethyl fumarate (as of 1st of Sept 2021), representing 1,119,293 patient-years of exposure (as of 30th Jun 2021), across global clinical trial & post-marketing settings.12

Common (≥1/100 to <1/10) adverse reactions includes gastroenteritis, lymphopenia, leucopenia, burning sensation, hot flush, vomiting, dyspepsia, gastritis, gastrointestinal disorder, aspartate aminotransferase and alanine aminotransferase increased, pruritus, rash, erythema, proteinuria, feeling hot, albumin urine present and white blood cell count decrease. Very common (≥1/10) adverse reaction includes flushing, diarrhoea, nausea, abdominal pain upper, Abdominal pain, ketones measured in urine.13

For more information on dimethyl fumarate and diroximel fumarate please refer to the SmPC:  Summary of Product Characteristics (SmPC) – (emc) (

About EVOLVE-MS-1 and EVOLVE-MS-25,6,14

EVOLVE-MS-1 is an ongoing, open-label, 96-week, phase 3 study assessing diroximel fumarate safety, tolerability, and efficacy in RRMS patients. The primary endpoint was safety and tolerability; efficacy endpoints were exploratory. The interim finding, as of September 2020; 1057patients were enrolled; median exposure was 2.0 (range, 0.0–2.1) years. Adverse events (AEs) occurred in 88% (932/1057) of patients, the majority were mild (29%; 307/1057) or moderate (50% 527/1057) in severity. Overall treatment discontinuation was 8%; and <1% due to GI AEs. At week 96, mean number of gadolinium-enhancing lesions was significantly reduced from baseline (63.6% p<0.0001) and adjusted annualised relapse rate (ARR)[§] was low 81% reduction (95% CI, 78.1–84.1) p < 0.0001) compared to 12 months before study entry.

EVOLVE-MS-2 was a phase 3, randomised, double-blind, head-to-head, 5-week study evaluating the gastrointestinal tolerability of diroximel fumarate 462 mg vs dimethyl fumarate 240 mg, administered twice daily in patients with relapsing–remitting multiple sclerosis, using two self-administered gastrointestinal symptom scales: Individual Gastrointestinal Symptom and Impact Scale (IGISIS) and Global Gastrointestinal Symptom and Impact Scale (GGISIS). The primary endpoint was the number of days with an IGISIS intensity score ≥2 relative to exposure. Other endpoints included the degree of gastrointestinal symptom severity measured by IGISIS/GGISIS and assessment of safety/tolerability. Results diroximel fumarate -treated patients experienced a statistically significant reduction (46%) in the number of days with an IGISIS symptom intensity score ≥2 compared with dimethyl fumarate -treated patients (rate ratio [95% confidence interval]: 0.54 [0.39–0.75]; p=0.0003). Lower rates of gastrointestinal adverse events (including diarrhoea, nausea, vomiting, and upper and lower abdominal pain) were observed with diroximel fumarate than dimethyl fumarate (34.8% vs 49.0%). Fewer patients discontinued diroximel fumarate than dimethyl fumarate because of adverse events (1.6% vs 5.6%) and gastrointestinal adverse events (0.8% vs 4.8%).

Biogen-163820 | Date of preparation: April 2022

Phase 2 LUMINARY Study of SAGE-718 in Patients with Mild Cognitive Impairment and Mild Dementia due to Alzheimer’s Disease

Sage Therapeutics presents promising results from LUMINARY Study

Data presented during the Emerging Science Session at the American Academy of Neurology’s Annual Meeting, April 2022

The LUMINARY Study is a Phase 2, open-label study evaluating the safety, tolerability and efficacy of SAGE-718 once daily in individuals with mild cognitive impairment and mild dementia due to Alzheimer’s disease

SAGE-718 demonstrated improvement across multiple tests of executive performance as well as improvement on key tests of learning and memory in the LUMINARY Study.

Sage Therapeutics, Inc., presented data from the Phase 2 LUMINARY Study that showed SAGE-718, a first-in-class, oral, positive allosteric modulator of the NMDA receptor, was generally well-tolerated and associated with improvement on multiple tests of executive performance and learning and memory in patients with mild cognitive impairment (MCI) and mild dementia due to Alzheimer’s disease (AD). The LUMINARY Study is part of CogNEXT, Sage’s early-stage trial platform designed to evaluate the therapeutic potential of SAGE-718 to treat cognitive deficits across a range of brain health disorders. The data was presented during the Emerging Science Session on Tuesday, April 5, at the 74th Annual Meeting of the American Academy of Neurology (AAN) in Seattle, US.

“Alzheimer’s disease is one of the greatest areas of unmet patient need, with an estimated global prevalence of more than 134 million people and few, if any, treatment options to specifically address mild cognitive impairment and mild dementia,” said Jim Doherty, Ph.D., Chief Development Officer at Sage.

We are encouraged by the positive results shared from the LUMINARY Study, which are consistent with signals suggesting improvement in cognitive performance seen across the SAGE-718 programme, including in people with Parkinson’s and Huntington’s disease. We look forward to learning more about the potential of SAGE-718 as we continue to advance our programme with multiple ongoing or planned Phase 2 studies.

Jim Doherty, Ph.D., Chief Development Officer at Sage

In the LUMINARY Study, a comprehensive battery of tests was used to assess multiple domains of cognitive performance in 26 patients receiving SAGE-718 3 mg once daily for 14 days. At Day 14, improvements from baseline were observed on multiple tests of executive functioning (Digit Symbol Substitution, Multitasking, One Touch Stockings, Spatial Working Memory, and 2-Back tests) and learning and memory (Pattern Recognition Memory and Verbal Recognition Memory tests).

Statistically significant improvement in the Montreal Cognitive Assessment (MoCA) (+2.3 points vs baseline) was observed at Day 28. As expected, no appreciable effect was observed on measures of simple attention/psychomotor speed, in keeping with the profile of SAGE-718 based on data to date. Functional assessments also captured notable improvement in some patients (Clinical Global Impressions Scales and Amsterdam Instrumental Activities of Daily Living Questionnaire), particularly on items measuring aspects of complex/higher order activities.

SAGE-718 was generally well-tolerated in the LUMINARY Study. Eight mild/moderate treatment-emergent adverse events (TEAE) were reported in seven patients. No serious adverse events or deaths were reported.

About the LUMINARY Study

The LUMINARY Study was an open-label, Phase 2 study evaluating SAGE-718, 3mg once daily for 14 days in patients with mild cognitive impairment and mild dementia due to AD. Patients aged 50–80 years with MoCA scores of 15-24 were included. Treatment-emergent adverse event incidence through Day 28 (primary endpoint), other safety outcomes (secondary endpoints) and cognitive and functional assessments were analysed.

About SAGE-718

SAGE-718, Sage’s first-in-class NMDA receptor PAM and lead neuropsychiatric drug candidate, is in development as a potential oral therapy for cognitive disorders associated with NMDA receptor dysfunction, potentially including Huntington’s disease, Parkinson’s disease and Alzheimer’s disease. Ongoing studies aim to evaluate whether SAGE-718 may have the potential to improve cognitive symptoms for these difficult-to-treat disorders. SAGE-718 is currently being studied in the ongoing Phase 2 DIMENSION Study, a double-blind placebo-controlled study in people with early to moderate cognitive impairment due to Huntington’s disease that is designed to evaluate the efficacy of once-daily dosed SAGE-718 over three months. Sage expects to initiate additional Phase 2 studies evaluating SAGE-718 in Huntington’s, Parkinson’s and Alzheimer’s diseases in 2022. In 2021, SAGE-718 received Fast Track Designation from the FDA for development of SAGE-718 as a potential treatment for Huntington’s disease.

For more information, please visit.

Liraglutide Improves Non-Motor Function and Activities of Daily Living in Patients with Parkinson’s disease

Abstract of poster presented at the AAN 2022, by Michele Tagliati, MD, FAAN

Treatment with liraglutide improves critical features of PD, including non-motor symptoms and activities of daily living. These results validate similar outcomes reported with other GLP-1 agonists in PD and offer new strategies to treat the constellation of PD symptoms.

Insulin resistance (IR) is a promising therapeutic target in Parkinson’s disease (PD). Currently, receptor agonists of glucagon-like peptide 1 (GLP-1) are the safest and most reliable means of reducing IR. Liraglutide is a powerful GLP-1 agonist currently approved for treatment of diabetes and obesity.

To test the therapeutic efficacy and safety of the GLP-1 agonist liraglutide in patients with idiopathic PD.

Design Methods
In this single-center, randomized, double-blind, placebo-controlled trial, PD patients received, in addition to regular medications, once-daily self-administered injections of liraglutide (1.2 or 1.8 mg, as tolerated) or placebo in a 2:1 study design for 52 weeks after titration. Primary outcomes included the adjusted difference in the OFF-state Movement Disorders Society Unified PD Rating Scale (MDS-UPDRS) part III, non-motor symptoms scale (NMSS) and Mattis Dementia Rating Scale (MDRS-2) at week 54. Efficacy analyses included patients who completed any post-randomization follow-up assessment.

63 patients were enrolled and randomized to liraglutide (n=42) or placebo (n=21). Twelve patients were early withdrawals, 4 of whom completed week 28 evaluation. Primary analysis included 37 active and 18 placebo subjects. At 54 weeks, NMSS scores had improved by 6.6 points in the liraglutide group and worsened by 6.5 points in the placebo group, a 13.1 point adjusted mean difference (p=0.07). MDS-UPDRS part III and MDRS-2 score changes from baseline did not significantly differ between active and placebo. Secondary outcome analysis revealed a significant improvement in MDS-UPDRS part-II scores in the treatment group (-4.1 points, p=0.001). Injection site reactions and gastrointestinal symptoms were common AEs. Eleven serious AEs were reported, none of which related to the study intervention.

Treatment with liraglutide improves critical features of PD, including non-motor symptoms and activities of daily living. These results validate similar outcomes reported with other GLP-1 agonists in PD and offer new strategies to treat the constellation of PD symptoms.

Cenobamate (ONTOZRY®) now available in The Netherlands

Angelini Pharma, an international pharmaceutical company part of the privately held Italian Angelini Group announced on 4 April 2022 that ONTOZRY® (cenobamate) is now available in the Netherlands for the adjunctive treatment of focal-onset seizures with or without secondary generalisation in adults patients who have not been adequately controlled despite an history of treatment with at least two anti-epileptic medicinal products. The product obtained approval from The European Medicines Agency in March ’21.2

There are an estimated 84 000 people in the Netherlands with epilepsy. Approximately 40% of adult patients with focal epilepsy have inadequate control of seizures after treatment with two anti-seizure medications (ASMs).3

Safety and efficacy of this product has been evaluated in three key trials involving over 1,900 patients.1,4,5 The pivotal trial (study 017) published in The Lancet Neurology1 is a multicenter, double-blind, randomised, placebo-controlled trial has demonstrated that cenobamate at doses of 100 mg, 200 mg, and 400 mg/day significantly improved seizure control versus placebo for adult patients with focal-onset seizures taking 1-3 ASMs. 1

The product demonstrated significantly higher responder rates (percentage of patients achieving ≥50% reduction in seizures) across all doses during the 12-week maintenance phase compared to placebo. The responder rates were 40% (p=0.036), 56% (p<0.001), and 64% (p<0.001), for the 100 mg, 200 mg, and 400 mg groups, respectively, compared to 25% in the placebo arm. Furthermore, 4% (not significant), 11% (p=0.002), and 21% (p<0.001), of patients treated with this product 100 mg, 200 mg and 400 mg per day, respectively, reported zero focal-onset seizures (100% seizure freedom) compared with only 1% of placebo treated patients during the maintenance phase.1

The global disease burden of epilepsy is high.6,7 A diagnosis of epilepsy confers significant disability on the individual, including physical, psychological, and social issues that negatively impact self-esteem, family environment, relationships, leisure and working life .6,8

In addition, people with epilepsy whose seizures are poorly controlled have higher morbidity and mortality rates, and often experience comorbid illnesses, social stigmatization, and an impaired quality of life.9,10

The product, which was discovered by SK Biopharmaceuticals and SK life science that have partnered with Angelini Pharma for the European market, marks a therapeutic breakthrough in managing the disease, and bringing hope to patients living with epilepsy.11


  1. Krauss GL et al. Safety and efficacy of adjunctive cenobamate (YKP3089) in patients with uncontrolled focal seizures: a multicenter, double-blind, randomised, placebo-controlled, dose-response trial. Lancet Neurol. 2020 Apr;19(4):288-289.
  3. Chen Z, et al. JAMA Neurol. 2018;75(3):279–286.
  4. Chung SS et al. Neurology. 2020;94(22):e2311–e2322.
  5. Sperling MR et al. Epilepsia. 2020;61(6):1099–1108
  6. Epilepsy: a public health imperative. Geneva: World Health Organization; 2019. Licence: CC BY-NC-SA 3.0 IGO.
  7. ILAE/IBE/WHO. Global Campaign Against Epilepsy: Out of the Shadows. 2003.
  8. Kaiser S, et al. Long-term follow-up of topiramate and lamotrigine: a perspective on quality of life. Seizure. 2002;11:356–360.
  9. Engel J. Bringing epilepsy out of the shadows. Neurol. 2003;60(9):1412.
  10. Engel J. Approaches to refractory epilepsy. Ann Indian Acad Neurol. 2014;17(Suppl 1):S12–7.
  11. Specchio N, et al. Int. J. Mol. Sci. 2021, 22, 9339.
  12. Cenobamate prescribing information. FDA. Last accessed: January 2022.
  13. Guignet Met al, Epilepsia. 2020 Oct 16. doi: 10.1111/epi.16718.
  14. Anderson LL et al., Epilepsia 2014; 55(8):1274-1283.
  15. Stafstrom CE, Epilepsy Curr 2007; 7(1):15-22.
  16. Vreugdenhil M et al., Eur J Neurosci., 2004; 19: 2769-2778.
  17. White HS et al, Epilepsy Res. 1997;28(3):167-79.
    18 NCT03678753

About Angelini Pharma

Angelini Pharma is an international pharmaceutical company, part of the Italian privately-owned Angelini Group with a UK affiliate established in 2021. Angelini Pharma is committed to helping patients in the therapeutic areas of Mental Health (including Pain), Rare Diseases and Consumer Healthcare. In particular, Angelini Pharma is committed to brain health – working every day to reduce and mitigate neurological disorders, while restoring and protecting mental health and cognitive function.

Over the past 50 years, in the field of mental health, Angelini Pharma has gained international recognition for its substantial efforts to improve the management of patients with mental health disorders thanks to important, internally developed molecules (such as trazodone) and its commitment to fighting mental-health stigma.

Angelini Pharma operates directly in 15 countries employing almost 3,000 people and commercialises its products in more than 50 countries through strategic alliances with leading international pharmaceutical groups.

In January 2021, Angelini Pharma announced that they concluded a definitive merger agreement under which Angelini Pharma acquired Arvelle Therapeutics. As a result, Angelini Pharma has the exclusive license to commercialise cenobamate in the European Union and other countries in the European Economic Area (Switzerland and the UK).

About Cenobamate

Cenobamate was discovered and developed by SK Biopharmaceuticals and SK life science and is an FDA and EMA-approved ASM for the treatment of partial-onset seizures in adults (also known as focal-onset seizures). Cenobamate is commercially available in the US under the trademark XCOPRI®.12

Cenobamate is a novel small molecule that provides a dual, complementary mechanism of action aimed at treatment of seizures.13,14 Cenobamate at clinically relevant concentrations, acts both as a positive allosteric modulator of GABAA receptors at a non-benzodiazepine binding site and preferentially blocks the persistent sodium current.9,14 The dual mechanism of action of cenobamate suggests that it has the potential to both prevent seizure initiation and limit seizure spread.15;16,17

Long-term data of cenobamate is being studied in the open-label extensions of the double-blind placebo control trials as well as the open-label safety study in adults with uncontrolled focal-onset seizures.5 Additionally, the product is being assessed in an ongoing randomised, double-blind, placebo-controlled trial evaluating its safety and efficacy as adjunctive therapy in patients with primary generalised tonic-clonic seizures. (NCT03678753)18

Cenobamate has recently gained recognition by healthcare regulatory bodies in the United Kingdom and Germany given its potential use in treatment resistant focal-onset seizures in epilepsy. The drug is available in Europe including Germany, Sweden, Denmark, UK and the Netherlands under the trademark ONTOZRY®.

UPLIZNA® (inebilizumab-cdon) Effective for People with Newly-Presenting Neuromyelitis Optica Spectrum Disorder (NMOSD)

Horizon Therapeutics plc announced on 31 March, 2022 the presentation of a post-hoc analysis from the N-MOmentum Phase 3 pivotal trial of UPLIZNA, showing that the medicine was safe and effective in NMOSD patients who were treated with UPLIZNA after having only one attack. These data were presented during a poster session at the American Academy of Neurology (AAN) 2022 Annual Meeting in Seattle April 2-7 and virtually April 24-26, 2022. UPLIZNA is the first and only FDA-approved CD19+ B-cell-depleting monotherapy proven to reduce the risk of attacks in adults with NMOSD who are anti-aquaporin-4 (AQP4) antibody positive.

This analysis aimed to clarify how prior history of attacks might affect the response to UPLIZNA by evaluating the medicine’s effect among individuals with newly-presenting NMOSD who were enrolled in the 28-week randomized, placebo-controlled period of the trial after their first attack compared to individuals with a history of two or more attacks.

Key analysis findings:

  • Of the 37 study participants who had experienced only one attack before joining the study, 4.2% (1/24) of those who were treated with UPLIZNA experienced an attack compared to 23.1% (3/13) of those who were treated with placebo.
  • Of the 176 study participants who had experienced more than one attack before joining the study, 12.4% (17/137) of those who were treated with UPLIZNA experienced an attack compared to 48.7% (19/39) of those who were treated with placebo.
  • No significant differences in attacks or Expanded Disability Status Scale (EDSS) worsening were found between participants with one pre-study attack and those with two or more pre-study attacks.
  • Treatment-emergent adverse events among those enrolled after their first attack were consistent with pivotal trial outcomes.

“These data are important because physicians see NMOSD patients at varying stages of their illness and it is helpful to understand how UPLIZNA might benefit patients at disease onset as well as those who have had more than one attack,” said Bruce Cree, MD, PhD, MAS, professor of clinical neurology at the University of California San Francisco Weill Institute for Neurosciences and primary study investigator. “In this sub-analysis of the N-MOmentum pivotal trial, which is the largest clinical trial conducted in NMOSD, UPLIZNA shows comparable efficacy in patients who had only one attack to those who have had two or more attacks. With this information, physicians can feel confident that patients may stop experiencing attacks after being treated with UPLIZNA regardless of how many previous attacks they experienced.”

In addition, an analysis from the N-MOmentum trial was presented showing long-term treatment with UPLIZNA improved pain outcomes in patients with NMOSD. Pain is a common, debilitating symptom of NMOSD that can dramatically impact daily activities. Previously presented data demonstrated improvements in pain scores after treatment with UPLIZNA. The new analysis builds on those findings by showing a durable, long-term benefit in managing pain, with year-over-year improvements from baseline (average of 6.57 points after one year, 7.08 after two years and 7.96 after three years) as measured by the 36-item short-form survey body pain subscore (SF36-BPS).

These rigorous analyses from the UPLIZNA pivotal trial provide compelling insights into the real value that UPLIZNA may provide as a novel option for people living with NMOSD. As physicians gain more experience with UPLIZNA, they can see how these clinical data translate into outcomes within their practices and potentially help more patients gain greater control over this challenging disease.”

Kristina Patterson, MD, PhD, medical director, neuroimmunology, Horizon.


  1. Ajmera MR, Boscoe A, Mauskopf J, Candrilli SD, Levy M. Evaluation of comorbidities and health care resource use among patients with highly active neuromyelitis optica. J Neurol Sci. 2018;384:96-103.
  2. What is NMO? Guthyjacksonfoundation.org Accessed April 15, 2021.
  3. Layman’s Guide to NMO. Sumairafoundation.org Accessed April 25, 2021.
  4. Liu Y, et al. A tract-based diffusion study of cerebral white matter in neuromyelitis optica reveals widespread pathological alterations. Mult Scler. 2011;18(7):1013-1021.
  5. Chihara N, et al. Interleukin 6 signaling promotes anti-aquaporin-4 autoantibody production from plasmablasts in neuromyelitis optica. PNAS. 2011;108(9):3701-3706.
  6. Duan T, Smith AJ, Verkamn AS. Complement-independent bystander injury in AQP4-IgG seropositive neuromyelitis optica produced by antibody dependent cellular cytotoxicity. Acta Neuropathologica Comm. 2019;7(112).
  7. Beekman J, et al. Neuromyelitis optica spectrum disorder: patient experience and quality of life. Neural Neuroimmunol Neuroinflamm. 2019;6(4):e580.
  8. Kimbrough DJ, et al. Treatment of neuromyelitis optica: review and recommendations. Mult Scler Relat Disord. 2012;1(4):180-187.
  9. Baranello RJ, Avasarala, JR. Neuromyelitis optica spectrum disorders with and without aquaporin 4 antibody: Characterization, differential diagnosis, and recent advances. J Neuro Ther. 2015;1(1):9-14.
  10. Wingerchuk DM. Neuromyelitis optica: effect of gender. J Neurol Sci. 2009;286(1-2):18-23.
  11. Flanagan EP, et al. Epidemiology of aquaporin-4 autoimmunity and neuromyelitis optica spectrum. Ann Neurol. 2016;79(5):775-783.

About Neuromyelitis Optica Spectrum Disorder (NMOSD)

NMOSD is a unifying term for neuromyelitis optica (NMO) and related syndromes. NMOSD is a rare, severe, relapsing, neuroinflammatory autoimmune disease that attacks the optic nerve, spinal cord, brain and brain stem.1,2 Approximately 80 percent of all patients with NMOSD test positive for anti-AQP4 antibodies.3 AQP4-IgG binds primarily to astrocytes in the central nervous system and triggers an escalating immune response that results in lesion formation and astrocyte death.4

Anti-AQP4 autoantibodies are produced by plasmablasts and plasma cells. These B-cell populations are central to NMOSD disease pathogenesis, and a large proportion of these cells express CD19.5 Depletion of these CD19+ B cells is thought to remove an important contributor to inflammation, lesion formation and astrocyte damage. Clinically, this damage presents as an NMOSD attack, which can involve the optic nerve, spinal cord and brain.4,6 Loss of vision, paralysis, loss of sensation, bladder and bowel dysfunction, nerve pain and respiratory failure can all be manifestations of the disease.7 Each NMOSD attack can lead to further cumulative damage and disability.8,9 NMOSD occurs more commonly in women and may be more common in individuals of African and Asian descent.10,11



UPLIZNA is indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive.


UPLIZNA is contraindicated in patients with:

  • A history of life-threatening infusion reaction to UPLIZNA
  • Active hepatitis B infection
  • Active or untreated latent tuberculosis


Infusion Reactions: UPLIZNA can cause infusion reactions, which can include headache, nausea, somnolence, dyspnea, fever, myalgia, rash or other symptoms. Infusion reactions were most common with the first infusion but were also observed during subsequent infusions. Administer pre-medication with a corticosteroid, an antihistamine and an anti-pyretic.

Infections: The most common infections reported by UPLIZNA-treated patients in the randomized and open-label periods included urinary tract infection (20%), nasopharyngitis (13%), upper respiratory tract infection (8%) and influenza (7%). Delay UPLIZNA administration in patients with an active infection until the infection is resolved.

Increased immunosuppressive effects are possible if combining UPLIZNA with another immunosuppressive therapy.

The risk of hepatitis B virus (HBV) reactivation has been observed with other B-cell-depleting antibodies. Perform HBV screening in all patients before initiation of treatment with UPLIZNA. Do not administer to patients with active hepatitis.

Although no confirmed cases of Progressive Multifocal Leukoencephalopathy (PML) were identified in UPLIZNA clinical trials, JC virus infection resulting in PML has been observed in patients treated with other B-cell-depleting antibodies and other therapies that affect immune competence. At the first sign or symptom suggestive of PML, withhold UPLIZNA and perform an appropriate diagnostic evaluation.

Patients should be evaluated for tuberculosis risk factors and tested for latent infection prior to initiating UPLIZNA.

Vaccination with live-attenuated or live vaccines is not recommended during treatment and after discontinuation, until B-cell repletion.

Reduction in Immunoglobulins: There may be a progressive and prolonged hypogammaglobulinemia or decline in the levels of total and individual immunoglobulins such as immunoglobulins G and M (IgG and IgM) with continued UPLIZNA treatment. Monitor the level of immunoglobulins at the beginning, during, and after discontinuation of treatment with UPLIZNA until B-cell repletion especially in patients with opportunistic or recurrent infections.

Fetal Risk: May cause fetal harm based on animal data. Advise females of reproductive potential of the potential risk to a fetus and to use an effective method of contraception during treatment and for 6 months after stopping UPLIZNA.

Adverse Reactions: The most common adverse reactions (at least 10% of patients treated with UPLIZNA and greater than placebo) were urinary tract infection and arthralgia.

For additional information on UPLIZNA, please see Prescribing Information at

About Horizon

Horizon is focused on the discovery, development and commercialisation of medicines that address critical needs for people impacted by rare, autoimmune and severe inflammatory diseases.