Author: Rachael Hansford

Cannabis-based medicine for neurodegenerative diseases

Posted on October 9, 2024 by - Alzheimer's Disease, Amyotrophic Lateral Sclerosis (ALS), Dementia, Movement Disorders, Parkinson’s Disease

Avextra announces the approval of NEUROBIS by the Italian Medicines Agency: A Phase II clinical trial

  • The Italian Medicines Agency AIFA and the Italian Ministry of Health have granted formal approval for NEUROBIS; a multi-centre Phase II study to evaluate safety, and efficacy of an Avextra oral cannabinoid formulation for managing the symptoms of patients suffering from neurodegenerative diseases such as ALS, Alzheimer’s disease and Parkinson’s disease.
  • NEUROBIS is the second Phase 2 clinical trial supported by Avextra.
  • NEUROBIS is one of the few randomised, placebo controlled, double-blind trial with a Cannabis-based medicine to be conducted at multiple sites in Italy and a study of this robust scientific nature aligns perfectly with Avextra’s clinical plan.
  • The study is funded by a grant from the Italian Ministry of Health signifying the support of regulators in gathering of clinical evidence for Cannabis-based medicines.

Avextra AG, a European manufacturer and developer of Cannabis-based medicines located in Germany, has announced that both the Italian Medicines Agency AIFA and the Italian Ministry of Health have granted formal approval for a multi-centre Phase II study to evaluate safety, and efficacy of an Avextra oral formulation in managing the symptoms of patients suffering from Amyotrophic Lateral Sclerosis (ALS), Alzheimer’s disease and Parkinson’s disease. The study, being conducted under the name NEUROBIS, is one of the few randomised, placebo controlled, double-blind trials to be conducted with a Cannabis-based medicine at multiple sites in Italy.

Avextra is partnering with the sponsor of NEUROBIS, the AOU Maggiore della Carità in Novara, Italy for a second company-supported Phase II clinical trial. The principal investigator is Prof. Dr. Letizia Mazzini, a Neurologist with over thirty years of experience in clinical research and Director of the Neurology Division at AOU Maggiore della Carità as well as Director of the ALS Regional Expert Centre at Department of Translational Medicine at the University of Piemonte Orientale. The study was funded by the Bando Ricerca Finalizzata through a grant from the Italian Ministry of Health as part of the National Health Research Programme and will be conducted across two sites over a 36-month period.

Preclinical studies and anecdotal evidence suggest that a specific CBD to THC ratio may play a role in managing symptoms such as pain, sleep deficiency and psychological stress for patients suffering from neurodegenerative conditions such as Alzheimer’s, Parkinson’s and Multiple Sclerosis. Avextra is committed to supporting and conducting clinical trials with the objective of developing safe, effective and regulatory approved medicines for patients where available treatment options fall short. Both the approval and the funding of NEUROBIS signify the supportive stance on the part of European regulatory bodies for gathering robust clinical evidence for Cannabis-based medicines.

“We are excited to support a second Phase II clinical trial NEUROBIS in partnership with a leading university hospital in Italy, the AOU Maggiore della Carità Novara,” said Dr. Bernhard Babel, CEO, at Avextra. “With two active Phase II clinical trials in BELCANTO in Germany and NEUROBIS in Italy, Avextra is uniquely positioned with the necessary skills and capabilities to design clinical trials and develop pharmaceutical IP with Cannabis-based medicines with the potential to improve patient’s quality of life.”

At our hospital, which is a reference centre for many neurodegenerative diseases, we observe an increase in the number of individuals affected by Dementia, Parkinson’s disease and ALS who require help with their symptoms. It is imperative to increase disease awareness and availability of treatment options to address these patient needs. As such we are grateful for the support of Avextra with their excellent clinical team and patient-centred approach

Prof. Letizia Mazzini, Principal Investigator for NEUROBIS

NEUROBIS is one component of Avextra’s larger clinical plan to gather the robust evidence to support use of its unregistered products in specific indications as it undergoes development of EMA-Registered Cannabis-based Medicines. The company is dedicated to working in collaboration with the medical community, regulators and other stakeholders to drive evidence-based innovation forward.

About Avextra AG
Avextra is one of Europe’s leading vertically-integrated medical cannabis operators focused on the development and production of regulator-approved medicines. Founded in 2019 and based out of Germany, the company works in close collaboration with doctors and pharmacists and researchers to develop and produce innovative cannabis-based medicines. Avextra controls the entire value chain – from cultivation in Portugal to EU-GMP certified extraction and manufacturing in Germany. Avextra operates across continental Europe through an expansive distribution network of multiple channels and strategically developed assets for these key markets.

Tolebrutinib in SPMS

Posted on September 27, 2024 by - Multiple Sclerosis

31% delay in time to onset of confirmed disability progression in non-relapsing Secondary Progressive Multiple Sclerosis (SPMS)

  • Phase 3 study data presented at ECTRIMS show that tolebrutinib, a brain-penetrant BTK inhibitor, addresses disability accumulation that occurs independently from relapse activity
  • Global regulatory submissions will begin in H2 2024

20 September, 2024: Positive results from the HERCULES phase 3 study in people with non-relapsing secondary progressive multiple sclerosis (nrSPMS) demonstrated that tolebrutinib delayed the time to onset of 6-month confirmed disability progression (CDP) by 31% compared to placebo (HR 0.69; 95% CI 0.55-0.88; p=0.0026). Further analysis of secondary endpoints demonstrated that the number of participants who experienced confirmed disability improvement increased by nearly two-fold, 10% with tolebrutinib compared to 5% with placebo (HR 1.88; 95% CI 1.10 to 3.21; nominal p=0.021). These results were presented on 20th September as a late-breaking presentation at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2024 conference in Copenhagen, Denmark.

“Secondary progressive multiple sclerosis is characterized by insidious worsening of disability over time, independent of relapses, and represents a critical unmet need because we don’t have effective treatments. The results of HERCULES show clearly that tolebrutinib delayed disability progression in people with nrSPMS – and some people even improved disability – by uniquely targeting the biological processes driving disease progression in the brain.” Dr. Fox is a paid advisor to Sanofi for the HERCULES trial.

Robert Fox, MD, Vice Chair of Research at Cleveland Clinic’s Neurological Institute, Cleveland, Ohio and Chair of the HERCULES Global Steering Committee

Based on preliminary analysis of the HERCULES study, there was a slight increase in tolebrutinib-treated patients of some adverse events. Liver enzyme elevations (>3xULN) were observed in 4.1% of participants receiving tolebrutinib compared with 1.6% in the placebo group, a side effect also reported with other BTK inhibitors in MS. A small (0.5%) proportion of participants in the tolebrutinib group experienced peak ALT increases of >20xULN, all occurring within the first 90 days of treatment. All but one case of liver enzyme elevations resolved without further medical intervention. Prior to the implementation of the revised study protocol with more stringent monitoring, one participant in the tolebrutinib arm received a liver transplant and died due to post-operative complications. To date, the implementation of more frequent monitoring has mitigated such serious liver sequelae. Other deaths in the trial were assessed as unrelated to treatment by investigator; deaths were even across the placebo and tolebrutinib arms at 0.3%.

Adverse events (≥10%*)tolebrutinib
N=752 (%)		placebo
N=375 (%)
COVID-19 infections192 (25.5%)85 (22.7%)
Urinary tract infections85 (11.3%)49 (13.1%)
*For participants receiving tolebrutinib

“With no treatment options currently available for the broad population of patients with secondary progressive multiple sclerosis, tolebrutinib has demonstrated its ability to delay disability by targeting underlying drivers of the disease. We look forward to discussing these results with healthcare authorities and are eager to see the results of tolebrutinib in primary progressive MS when they become available next year. We extend our deepest appreciation to the study participants, their families, and the healthcare professionals involved in these trials.
Houman Ashrafian, MD, PhD, Head of Research & Development, Sanofi

The GEMINI 1 and 2 phase 3 study results of tolebrutinib compared to Aubagio (teriflunomide), a standard-of-care treatment, in participants with relapsing multiple sclerosis (RMS) were also presented as a late-breaking presentation at ECTRIMS. Both studies did not meet their primary endpoints of statistically significant improvement in annualised relapse rates (ARR) compared to Aubagio. However, in the key secondary endpoint, a pooled analysis of data from GEMINI 1 and 2, tolebrutinib delayed the time to onset of 6-month confirmed disability worsening (CDW) by 29% (HR 0.71; 95% CI: 0.53-0.95; nominal p=0.023). The results of the 29% delay in CDW endpoint in participants with RMS are in line with the 31% delay in CDP observed in participants with nrSPMS. The significant impact of tolebrutinib on disability accumulation versus Aubagio, in the absence of a statistically superior impact on relapses, suggests that tolebrutinib may address smoldering neuroinflammation, which manifests as progression independent of relapses.

Furthermore, results showed historically low ARR in the Aubagio arm in both GEMINI 1 and 2, and no difference was observed between Aubagio and tolebrutinib in a pooled analysis. These relapse rates amount to approximately 1 relapse every 8 years.

 tolebrutinib ARRAubagio ARR
GEMINI 1
(adjusted rate ratio 1.06; 95% CI: 0.80 to 1.39; p=0.67)		0.130.12
GEMINI 2
(adjusted rate ratio 1.00; 95% CI: 0.75 to 1.32; p=0.98)		0.110.11
Pooled analysis
(adjusted rate ratio 1.03; 95% CI: 0.84 to 1.25; p=0.80)		0.120.12

In preliminary analysis of the GEMINI 1 and 2 pooled safety data, adverse events observed between the tolebrutinib and Aubagio arms were generally balanced. Liver enzyme elevations (>3x ULN) were observed in 5.6% of participants receiving tolebrutinib compared with 6.3% of participants receiving Aubagio, a side effect reported with other BTK inhibitors in MS and resolved without further medical intervention. A small (0.5%) proportion of participants in the tolebrutinib group experienced peak ALT increases of >20xULN, all occurring within the first 90 days of treatment. Deaths were balanced across the Aubagio and tolebrutinib arms, at 0.2% and 0.1% respectively, and were assessed as unrelated to treatment by investigator.

Adverse events (≥10%*)Tolebrutinib
N=933 (%)		Aubagio
N=939 (%)
COVID-19 infections225 (24.1%)252 (26.8%)
Nasopharyngitis119 (12.8%)105 (11.2%)
Headache117 (12.5%)98 (10.4%)

*For participants receiving tolebrutinib

Study results will form the basis for future discussions with global regulatory authorities with submissions starting in H2 2024. Tolebrutinib is currently under clinical investigation, and its safety and efficacy have not been evaluated by any regulatory authority. 

The PERSEUS phase 3 study in primary progressive MS is currently ongoing with study results anticipated in H2 2025.

Spinocerebellar ataxia – troriluzole topline results

Posted on September 25, 2024 by - Movement Disorders, Neurodegenerative diseases

Biohaven achieves positive results in pivotal study

September 23 2024

  • Troriluzole 200 mg dosed orally, once daily, in patients with spinocereballar ataxia (SCA) met the study’s primary endpoint on the change from baseline in the modified functional Scale for the Assessment and Rating of Ataxia (f-SARA) at 3 years in all study population genotypes.
  • Troriluzole also showed statistically significant superiority after both 1 and 2 years of treatment.
  • Troriluzole achieved statistically significant superiority on 9 consecutive, prespecified primary and secondary endpoints.
  • SCA patients treated with troriluzole showed a 50-70% slowing of disease progression, representing 1.5-2.2 years delay in disease progression over the 3-year study period.
  • Biohaven plans to submit a New Drug Application (NDA) to the US Food and Drug Administration (FDA) for troriluzole in the treatment of all spinocereballar ataxia (SCA) genotypes in 4Q 2024. The application is eligible for a priority review given orphan drug and fast-track designations previously granted by FDA.

Biohaven Ltd have announced positive topline results from pivotal Study BHV4157-206-RWE (NCT06529146) demonstrating the efficacy of troriluzole on the mean change from baseline in the f-SARA after 3 years of treatment. The study achieved the primary endpoint and showed statistically significant improvements on the f-SARA at years 1 and 2 (Figure 1). SCA is a rare, progressively debilitating neurodegenerative disease that affects approximately 15,000 people in the United States and 24,000 in Europe and the UK. There are no FDA approved treatments for SCA.

Figure 1: f-SARA Change from baseline demonstrating troriluzole reduced spinocerebellar ataxia disease progression vs US Natural History External Control
Figure 1: f-SARA Change from baseline demonstrating troriluzole reduced SCA disease progression vs US Natural History External Control

Collectively, data across multiple analyses demonstrate a robust and clinically meaningful slowing of disease progression in SCA patients. These treatment benefits translate into a 50-70% slower rate of decline compared to untreated patients, representing 1.5-2.2 years delay in disease progression over the 3-year study period. Additionally, in a responder sensitivity analysis, disease progression when defined by a 2 point or greater worsening on the f-SARA at 3 years showed an odds ratio (OR) of 4.1 (95% CI: 2.1, 8.1) for the untreated external control arm versus troriluzole treated subjects (p < 0.0001; pooled analysis).

Dr. Susan Perlman, Director of Ataxia Clinic and Neurogenetics Clinical Trials at the David Geffen School of Medicine at UCLA stated, “SCA is a debilitating, relentlessly progressive disease that destroys quality of life, leaving patients unable to care for themselves, walk, or speak. Troriluzole is the very first treatment to show a delay in disease progression that can give patients additional years of independence, where they can walk without assistance, continue to work, play with their children, and participate in daily activities. This is an exciting and hopeful moment for the SCA community.” 

Study BHV4157-206-RWE was designed, in discussion with the US Food and Drug Administration (FDA), to assess the effectiveness of troriluzole in SCA after 3 years of treatment as measured by the change from baseline in the f-SARA. The study utilised Phase 3 data and an external control of matched, untreated SCA subjects from the US Clinical Research Consortium for the Study of Cerebellar Ataxia (CRC-SCA) in accordance with FDA’s Guidance on Real-World Evidence (RWE) of effectiveness. All endpoints were prespecified, and both the study protocol and statistical analysis plan were submitted to, and reviewed by, FDA prior to topline data analysis. The new analysis doubled the previously available 3 year data with 63 subjects now completing 3 years of treatment with troriluzole and matched to the external control arm. Propensity Score Matching (PSM) was used to ensure that untreated patients from the CRC-SCA study were rigorously matched to treated patients from Study BHV4157-206 on baseline characteristics.  The primary objective was to examine the treatment effects of troriluzole for up to 3 years, by comparing data on the f-SARA from patients treated with troriluzole in Study BHV4157-206 to untreated patients from the natural history study. Troriluzole-treated patients demonstrated statistically significant and sustained benefits at years 1, 2 and 3 on the f-SARA compared to a rigorously matched natural history control.

Additionally, prespecified analyses in the protocol employed a separate, independent natural history control from the European SCA natural history study (EUROSCA) for global regulatory purposes. Results using the EUROSCA patients, in addition to a pooled analysis using both CRC-SCA and EUROSCA patients, as the external controls were also statistically significant and consistent with the primary efficacy analysis at all timepoints (see Figure 2 and Figure 3). The addition of EUROSCA data increased the external control sample size and added to the robustness of the statistically significant treatment differences at years 1, 2, and 3, favoring troriluzole.

Figure 2: f-SARA change from baseline demonstrating troriluzole reduced spinocerebellar ataxia disease progression vs Independent EU Natural History External Control
Figure 2: f-SARA change from baseline demonstrating troriluzole reduced SCA disease progression vs Independent EU Natural History External Control
Figure 3: f-SARA change from baseline demonstrating troriluzole reduced spinocerebellar ataxia disease progression vs Pooled US and EU Natural History External Control
Figure 3: f-SARA change from baseline demonstrating troriluzole reduced SCA disease progression vs Pooled US and EU Natural History External Control

Jeremy Schmahmann, M.D., Professor of Neurology at Harvard Medical School and Founding Director of the Ataxia Center at Massachusetts General Hospital commented:

The stabilisation of SCA symptoms as reflected by the topline data at 3 years along with the previously reported reductions in falls show the therapeutic potential of troriluzole. I cannot underscore enough the impact of a potential treatment that can slow SCA disease progression and the effect on patients and caregivers who have helplessly watched generations of family members deteriorate and die from SCA. These new data provide support for troriluzole as a safe and effective once daily treatment for patients with SCA.

Spinocerebellar ataxia is a group of dominantly inherited neurodegenerative disorders characterised by progressive loss of voluntary motor control and atrophy of the cerebellum, brainstem and spinal cord. Patients experience significant morbidity, including progression to a wheelchair, impaired gait leading to falls, inability to communicate due to speech impairment, difficulty swallowing, and premature death. While signs and symptoms can appear anytime from childhood to late adulthood, SCA typically presents in early adulthood and progresses over a number of years. Currently, there are no FDA-approved treatments and no cure for SCA.

Based upon the topline data from Study BHV4157-206-RWE, and previous safety and efficacy data from the troriluzole development programme in SCA, Biohaven plans to submit a New Drug Application (NDA) to the FDA in Q4 2024. The troriluzole development programme has generated the largest clinical trial dataset in SCA and now has follow-up in some patients treated with troriluzole for over 5 years.  Biohaven has previously received both Fast-Track and Orphan drug designation (ODD) from the FDA, and ODD from the European Medicines Agency, for troriluzole in SCA. An NDA with ODD is eligible for priority FDA review. Biohaven will be prepared to commercialise SCA in the US in 2025, if ultimately approved, based on potential priority review timelines.

US launch of CREXONT® for Parkinson’s disease

Posted on September 24, 2024 by - Parkinson’s Disease

23 September 2024: Amneal Pharmaceuticals has announced that it has launched CREXONT® (carbidopa and levodopa) extended-release capsules for the treatment of Parkinson’s disease. CREXONT® is a novel, oral formulation of carbidopa/levodopa (CD/LD) that combines both immediate-release granules and extended-release pellets.

“We are pleased to launch CREXONT and make it broadly available to healthcare providers and patients. The product’s innovative formulation provides a longer duration of “Good On” time with less frequent dosing compared to immediate release CD/LD. As a leader in the Parkinson’s space, Amneal has a long history of working closely with movement disorder specialists and neurologists. We are excited to build on this foundation with the rollout of a comprehensive education program and extensive services to help healthcare providers and patients access this innovative therapy,” said Joe Renda, Senior Vice President, Chief Commercial Officer – Specialty.

CREXONT is now broadly available at US pharmacies, through prescription.

International Congress of Parkinson’s Disease and Movement Disorders

Amneal will hold the following CREXONT events at this year’s International Congress of Parkinson’s Disease and Movement Disorders being held in Philadelphia, PA on Sept. 27 – Oct. 1, 2024:

  • Dr. Robert Hauser, CREXONT principal investigator, will present a launch symposium introducing CREXONT on Friday, Sept. 27, 2024 at 1:30 pm ET entitled: Innovation in “On” time is here: introducing CREXONT® (carbidopa and levodopa) extended-release capsules.
  • An abstract will be presented highlighting motor states upon awakening with CREXONT (IPX203):Abstract Title: Impact of IPX203 on Parkinson’s patients’ motor states upon awakening: analysis of patient diary data
    Abstract Number: 688
    Abstract Category: Parkinson’s Disease: Clinical Trials
    Presentation Date and Time: Sunday, September 29, 1:00-3:00 pm EDT
    Poster Hall: Exhibit Hall A

For additional information about the International Congress of Parkinson’s Disease and Movement Disorders, please click here.

Rewriting the story of dementia

Posted on September 24, 2024 by - Alzheimer's Disease, Dementia

Poetry book challenges mainstream media portrayal

In the palm of a spider’s hand by Gerald King, who was diagnosed with young-onset Alzheimer’s at 55, aims to challenge the dehumanising narratives about dementia perpetuated by mainstream media. This publication seeks to redefine how we understand and engage with the lived dementia experience. King’s words liken Alzheimer’s to “still waters laced with rough skinned crocodiles,” question “why me?” and highlight the vital importance of comfort, kindness, patience and understanding. 

Mainstream media too often reduces people with dementia to passive, voiceless shadows – an image perpetuated by stock photos of vacant faces and constant dependency. But In the palm of a spider’s hand, written entirely post-diagnosis by Gerald King, is a testament to the untapped potential of many living with dementia. 

King’s work is not just poetry; it pushes back against a narrative that too often writes off people with dementia as incapable or unable. His words are living proof that creativity and contribution don’t end upon diagnosis – they evolve.

Nichole Fernandez’s pivotal Images of Care study highlights the problem: media depictions of people with dementia overwhelmingly focus on dependency and decline, erasing their humanity and potential. But Gerald King’s book – envisioned, edited, designed and published by boom saloon, with print sponsorship from Canon, showcases the raw, unfiltered reality of living with dementia; a reality that is rich with emotion, intellect and creativity.

[Read ACNR dementia articles]

This publication is a call for more compassionate and accurate representations of dementia; to start a new conversation that empowers those living with the condition rather than marginalising them.

With an ageing population and rising dementia rates, the stories we tell – and how we tell them – matter more than ever. Gerald King’s poetry challenges perceptions, inspires action and reminds us of the strength and potential that lie within many living with the condition.

Sales of the book support boom saloon’s ongoing work to rewrite the story of dementia, via community projects which use creativity to inspire those facing challenges. Preorder via the website.

Rewriting the story of dementia, Gerald King at work on his poetry

Deutetrabenazine for Tardive Dyskinesia 

Posted on September 23, 2024 by - Movement Disorders

Teva Announces Long Term Efficacy and Safety of Deutetrabenazine in European Patients

  • RIM-TD open-label extension (OLE) study showed long-term improvement of Tardive Dyskinesia (TD) symptoms from treatment with deutetrabenazine over three years in European patients1
  • TD is an involuntary movement disorder that develops in around 15%-25% of patients taking antipsychotic medications for conditions such as schizophrenia, bipolar disorder, and major depressive disorder2,3
  • Data presented at the European College of Neuropsychopharmacology Congress (ECNP) in Milan 21-24 September 2024

21st September 2024: Teva Pharmaceutical Industries Ltd has announced that a new analysis from the European cohort of the RIM-TD open-label extension (OLE) study revealed that deutetrabenazine treatment of patients with Tardive Dyskinesia (TD) was associated with long term improvement of TD symptoms. The improvement in symptoms was sustained throughout the three-year study, and deutetrabenazine was well tolerated.1 The data were presented at the European College of Neuropsychopharmacology (ECNP) annual congress in Milan.

TD is a stigmatising and debilitating involuntary movement disorder characterised by repetitive movements of the tongue, lower face, jaw, and limbs, which develops in around 15%-25% of patients receiving antipsychotic medications for conditions such as schizophrenia, bipolar disorder, and major depressive disorder.2,3 

TD usually appears after 1-2 years of taking antipsychotic treatment and has a considerable impact on a patients’ functioning and quality of life.4 The condition has a high unmet medical need as limited treatment options are approved in Europe.5  

RIM-TD (Reducing Involuntary Movements in Participants with Tardive Dyskinesia) is a three-year study which enrolled patients who had completed one of the two pivotal deutetrabenazine phase 3 studies, ARM-TD6 and AIM-TD.7 Whilst RIM-TD was conducted in both the United States and Europe, the post hoc subgroup analysis focused on patients from the European countries.1

Treatment success was defined as ‘much improved’ or ‘very much improved’ on the Clinical Global Impression of Change (CGIC) or Patient Global Impression of Change (PGIC). The majority of patients achieved treatment success with 65% of patients for CGIC and 56% for PGIC. Deutetrabenazine was generally well tolerated, regardless of which arm of the two Phase 3 trials (treatment or placebo) the patients had previously been treated in.1

Co-author and presenter of the data, Dr Krzysztof Duma, Associate Medical Director, Teva Pharmaceuticals Europe said:

“Tardive Dyskinesia is a complex disorder that is difficult to treat and remains broadly underdiagnosed. Treating this condition still often results in dose reductions of antipsychotic medication that can impact the underlying psychiatric condition and lead to higher hospitalisation rates. The positive outcome of the study in the European cohort is similar to what we have observed in the overall and US population and gives us further evidence that deutetrabenazine can provide an effective treatment option.”

“Tardive Dyskinesia can cause great distress to patients and may be correlated with more severe symptoms and worse outcomes in patients with schizophrenia” said Pinar Kokturk, M.D. Vice President & Head of Medical Affairs Europe at Teva. “Management of Tardive Dyskinesia is sadly not optimal. Across Europe, guidelines for the management of TD are scarce or missing and there is no standard of care. Despite several treatments used in Europe, the majority have poor clinical evidence and are used off-label and there remains a high unmet need in the treatment of TD. This must change.”   

Deutetrabenazine has now been evaluated in ARM-TD, AIM-TD as well as RIM-TD, all of which demonstrated that the treatment provides rapid, sustained, and clinically meaningful improvements in motor function in patients with Tardive Dyskinesia.1,6,7

Deutetrabenazine is already approved in the United States and in a number of other markets worldwide.8

References

1. Hauser A. R et al. Long-Term Efficacy and Safety of Deutetrabenazine in a European Cohort of the RIM-TD Open-Label Extension Study. Presented at European College of Neuropsychopharmacology (ECNP) 21 Sept-24 Sept 2024, Milan. P2154

2.  Ricciardi L et al. Treatment Recommendations for Tardive Dyskinesia. The Canadian Journal of Psychiatry /La Revue Canadienne de Psychiatrie 2019, Vol. 64(6) 388-399.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591749/

3. Citrome et al. Deutetrabenazine for Tardive Dyskinesia: A systematic review of the efficacy and safety profile for this newly approved novel medication—What is the number needed to treat, number needed to harm and likelihood to be helped or harmed? The International Journal of Clinical Practice. 2017;71(11):e13030

4. Waln O, Jankovic J. An update on Tardive Dyskinesia: From phenomenology to treatment. Tremor other Hyperkinet Mov. 2013; 3: tre03-161-4138-1.

5 Takeuchi H, et al. Pathophysiology, prognosis and treatment of tardive dyskinesia. Therapeutic Advances in Psychopharmacology. 2022; 12:20451253221117313.

6. Fernandez H. H. et al. Randomized controlled trial of deutetrabenazine for Tardive Dyskinesia: The ARM-TD study. Neurology (2017).  May 23;88(21):2003-2010

7. Anderson A.E. et al. Deutetrabenazine for treatment of involuntary movements in patients with Tardive Dyskinesia (AIM-TD): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Psychiatry (2017). Aug;4(8):595-604.

8. Teva Pharmaceutical Indistries Limited. Dec 2023 United States Securities and Exchange Commission (Q4cdn.Com)

Triptans effective for acute migraine sufferers

Posted on September 21, 2024 by - Headache

Study suggests Triptans are the most effective medicine for adults who experience acute migraines

Findings of a study, in which researchers looked at 137 controlled trials that tested oral drugs commonly used to treat migraines, have been published in The British Medical Journal. The trials involved a total of 89,445 patients who were given one of 17 drugs or a placebo.

The paper was led by Professor Andrea Cipriani, Professor of Psychiatry at the University of Oxford and Director of the Oxford Health Clinical Research Facility, along with other researchers across Europe.

The article reports findings from the international AMADEUS (Acute Migraine Attacks: Different Effects of individUal drugS) study, which was funded by the National Institute for Health and Care Research (NIHR) Oxford Health Biomedical Research Centre and the Lundbeck Foundation.

Professor Andrea Cipriani said:

The best performing triptans should be considered as the preferred treatment of choice for migraine episodes owing to their ability to induce rapid and freedom from pain. Our findings pave the way to a precision medicine approach in clinical practice and should be used to help inform future guidelines about treatments for acute migraines to ensure that patients receive the best possible care.”

Triptans are a group of drugs that are often given as an alternative to painkillers if painkillers do not work. Triptans have a different mechanism of action and work by imitating the action of a brain chemical called 5- hydroxytryptamine, also known as serotonin.

Triptans, specifically eletriptan, rizatriptan, sumatriptan and zolmitriptan demonstrated the highest efficacy for pain relief at two hours and sustained pain relief over 24 hours.

Newer drugs, such as lasmiditan, rimegepant and ubrogepant were compared in the study and were found to be comparable to non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol but were not as effective as triptans.

Ibuprofen also emerged as a strong option for sustained pain freedom up to 24 hours post-dose.

Professor Cipriani added: “Triptans are currently widely underused. Their superior performance of triptans over newer, more expensive, drugs presents a path forward for cost-effective and accessible migraine treatment worldwide.”

Robert Music, chief executive of the Migraine Trust, said: “While triptans can be highly effective for some people with migraine, there are many who do not respond to them. Others experience intolerable side effects or are unable to take them including those with cardiovascular disease. Frequent use of triptans can also lead to medication overuse headache, which exacerbates the problem.

Finding a migraine treatment that works can be incredibly difficult and can take many years of painful trial and error, the consequences of which can lead to loss of employment, impact on finances and significantly reduced mental health.

Our focus should not be deprioritising newer treatments, instead making them more available when people require their use, so that individuals have greater options and choice.”

Phase 1 study of UB-312 shows promise in Parkinson’s disease

Posted on September 20, 2024 by - Parkinson’s Disease

In a study published in Nature Medicine on 18th September 2024, Parkinson’s patients reported improved daily movement with Vaxxinity’s Parkinson’s drug UB-312. The small trial, which included work from researchers at the University of Texas, the Mayo Clinic, and the Michael J. Fox Foundation for Parkinson’s Research, included only 20 people with Parkinson’s.

However, it describes what could potentially be two firsts for Parkinson’s disease: a diagnostic test and a potential immune-based treatment that works in a similar way to a vaccine. 

The target of the test and treatment is alpha synuclein, which aggregates abnormally in PD brains and destroys nerve cells.

Researchers have been investigating ways to measure and target these proteins. The company Vaxxinity developed an ‘active immune medicine’, to train the immune system to attack only abnormal versions of alpha synuclein —which are improperly folded.

“The idea is that patients should recognise their own misfolded proteins, and it is personalised because their own immune systems are doing the work,” says Dr Mark Frasier, chief scientific officer at the Michael J. Fox Foundation for Parkinson’s Research, which funded the testing part of the study.

Overall, people receiving the vaccine generated more antibodies against the abnormal alpha synuclein protein than those vaccinated with placebo, as measured by the Parkinson’s test. The test uses samples of cerebrospinal fluid to measure a person’s levels of abnormal alpha synuclein.

“What is unique about our technology is that it can stimulate the immune system to produce very, very specific antibodies against toxic forms of alpha synuclein, and do it in a safe way, which is reassuring,” says Jean-Cosme Dodart, senior vice president of research at Vaxxinity and senior author of the paper.

About half of the patients in the trial showed high levels of antibodies against the misfolded alpha synuclein, and most of these patients received the highest dose of the vaccine. They also scored the highest on motor and cognitive tests. There were too few patients to adequately assess any changes of Parkinson’s symptoms, but the researchers believe that longer follow-up with those tests, and potentially more frequent or higher doses of the vaccine, could lead to improvements in scores.

Overall, people receiving the vaccine generated more antibodies against the abnormal alpha synuclein protein than those vaccinated with placebo

FDA clearance for amyloid imaging software in Alzheimer’s disease

Posted on September 19, 2024 by - Alzheimer's Disease

GE HealthCare’s MIM Software division has received FDA clearance for software to image amyloid plaque in the brains of people with Alzheimer’s disease.

The automated MIMneuro programme analyses PET images from any scanner using injectable tracer agents with the aim of providing a standardised metric for one of the main aspects of Alzheimer’s pathology.

It aims to offer consistent measurements of brain tissue across various scanners and ranges from a score of 0 among people highly likely to have no amyloid buildups, to a high of 100 that represents the typical patient with Alzheimer’s.

With advances in pharmaceutical therapies over the past 18 months—including the FDA’s approvals of Eisai and Biogen’s Leqembi and Eli Lilly’s Kisunla — GE HealthCare has been positioning itself to provide the diagnostic support required before treatment.

PET imaging can help clinicians more confidently determine a patient’s amyloid status

Anja Mett, GE HealthCare’s global product leader for MI neurology