Author: Rachael Hansford

Trial failure for Jazz Pharmaceuticals’ cannabis-derived drug in MS

Jazz Pharmaceuticals nabiximols oromucosal spray did not meet the primary endpoint in a phase 3 trial, failing in its aim of improving Lower Limb Muscle Tone-6 (LLMT-6) between baseline and Day 21, as measured by the Modified Ashworth Scale (MAS).

The spray is formulated from extracts of the cannabis sativa plant and contains tetrahydrocannabinol (THC) and cannabidiol (CBD). It has been approved in 29 countries for adults with MS spasticity who have not responded adequately to other anti-spasticity treatments.

Jazz said it will continue to evaluate the spray for use in MS patients.

With 68 participants, the Release MSS1 trial was the first and smallest of three studies Jazz is conducting with the spray in MS. Release MSS3 is examining the improvement of muscle spasms in 446 MS patients over a 12-week period. Release MSS5 is investigating velocity-dependent lower-limb muscle tone over a 21-day period in 190 MS patients.

We look forward to additional data from two other ongoing trials that have the potential to support a US FDA new drug application submission

Rob Iannone, M.D., EVP, global head of research and development at Jazz Pharmaceuticals

Promising interim results for Ajovy

PEARL STUDY Interim data presented at the European Academy of Neurology 2022 shows that 54.7% of patients in the study had their monthly-migraine-days reduced by 50% or more over the six-month period from the start of treatment.

25th June 2022: Teva Pharmaceuticals Europe B.V. announced promising interim results from its Pan-European Real World study (PEARL), presented for the first time at the European Academy of Neurology (EAN) Congress in Vienna, Austria.

The two-year Pan-European Real World (PEARL) prospective, observational study of AJOVY® (fremanezumab), looks at its effectiveness in patients with chronic migraine or episodic migraine, and is an ongoing study sponsored by Teva Pharmaceuticals Europe BV.[i]  These findings further offer insight into the treatment of migraine in real-world clinical practice.

The interim findings were presented by Faisal Mohammad Amin, Associate Professor of Neurology at the University of Copenhagen, Denmark.  Out of the total planned 1100 patients in PEARL, 389 patients are included in the interim analysis presented.  These findings show that 54.7% of patients in the study had their monthly-migraine-days reduced by 50% or more, over the six-month period from the start of treatment.  Additionally improvements could be seen in migraine-related disability in the six-month period after the first dose.    

The study is particularly relevant to clinicians due its patient cohort, who come from 11 countries and approximately 100 study centres.1 This patient group illustrates both diverse populations and also a range of reimbursement settings which are important for treatment access in Europe.  

The study will continue to capture data on effectiveness, and safety of fremanezumab, as well as the reason for and the outcomes of stopping and re-starting treatments. 

Commenting on the findings, Professor Messoud Ashina, PEARL Coordinating Investigator from the Danish Headache Center and Department of Neurology in Rigshospitalet Glostrup, Denmark, said:

Patients with severe migraine could benefit from preventive therapy but usage of those treatments is far from optimal. These interim findings provide real-world evidence of how the burden of migraine can be reduced when the patient has access to monoclonal antibodies like fremanezumab – something neurologists around the world are already seeing in patients who did not respond to previous preventive treatments.

Dr. Danilo Lembo, Vice President and Head of EU Medical Affairs at Teva, said: “The PEARL study is encouraging as these findings confirm that preventive treatment of chronic and episodic migraine is appropriate with fremanezumab in a real world setting. Our commitment to real-world evidence studies helps clinicians to better understand the lived experience of people with migraine, support the evolution of best clinical practice and demonstrate the impact of migraine and what preventive treatments can achieve. ”

The real life experience of European patients being able to access preventive treatment is bleak. Beyond our own data and research, a recent study from the European Migraine and Headache Alliance showed that 40% of patients needed more than five years to access migraine treatments.[ii] We need real structural change to come from healthcare systems if we are to ultimately reduce the burden of migraine.

Dr. Danilo Lembo, Vice President and Head of EU Medical Affairs at Teva

Chronic migraine is defined as a headache occurring on 15 or more days per month for more than three months, which, on at least 8 days per month, has the features of migraine headache;[iii] episodic migraine is defined as having headaches on fewer than 15 days a month.[iv] The significant personal impact and burden of this severity of migraine has been shown in many studies including Teva’s own survey of 12,545 adults with migraine – ‘Beyond Migraine’, in which 45% said migraine impacts their ability to be a good partner and 42% to be a good parent, while 49% said migraine diminished their ability in the workplace. In terms of broader social impact, 46% reported hiding migraine from others.[v]

41 million people in Europe live with migraine[vi] and the disease is three times more common in women.[vii]  Migraine is the second leading cause of disability in the world and the first among young women.[viii] Migraine often begins at puberty and mostly affects people aged between 35 and 45 years.[ix] It strikes during people’s most productive years (late teens to 50s).[x]

Further reading

A publication in the journal Headache presented data that shows, for AJOVY®, there is no reduction in efficacy over a dosing period. This means that the efficacy of AJOVY® was similar at the end of the dosing period compared to the start of the same dosing period, immediately following treatment admininistration. Patients using AJOVY® therefore experience the benefits of treatment throughout the entire dosing period. See Blumenfeld AM, Stevanovic DM, Ortega M et al. No “wearing-off effect” seen in quarterly or monthly dosing of fremanezumab: Subanalysis of a randomized longterm study. Headache 2020; 60: 2431–2443.


References:

[i]Ashina, M. et al, PEARL study protocol. Pain management, 11(6), 647–654. (v0.1) – The two year Pan-European Real

World (PEARL) prospective, observational study of AJOVY® (fremanezumab)

2. KPMG, prepared for the European Migraine and Headache Alliance (EMHA). “Access to Care” project: final assessment. July 2021. [online] Available at: https://www.emhalliance.org/wp-content/uploads/ATC-EMHA-Dossier.pdf

[iii] Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. (2018). Cephalalgia, 38(1), 1–211. https://doi.org/10.1177/0333102417738202

[iv] Lipton, R. B., & Silberstein, S. D. (2015). Episodic and chronic migraine headache: breaking down barriers to optimal treatment and prevention. Headache, 55 Suppl 2, 103–126. https://doi.org/10.1111/head.12505_2

[v] Beyond Migraine – The Real You. Survey conducted 2020. Teva Pharmaceuticals. Data on file.

[vi] Stovner, L. J., Andrée, C., & Eurolight Steering Committee (2008). Impact of headache in Europe: a review for the Eurolight project. The journal of headache and pain, 9(3), 139–146. https://doi.org/10.1007/s10194-008-0038-6

[vii] Al-Hassany L, Haas J, Piccininni M, Kurth T, Maassen Van Den Brink A and Rohmann J.L. (2020) Giving Researchers a Headache – Sex and Gender Differences in Migraine. Front. Neurol. 11:549038. https://doi:10.3389/fneur.2020.549038

[viii] Steiner, T.J., Stovner, L.J., Jensen, R. et al. Migraine remains second among the world’s causes of disability, and first among young women: findings from GBD2019. J Headache Pain 21, 137 (2020). https://doi.org/10.1186/s10194-020-01208-0

[ix] Who.int. 2016. Headache disorders. [online] Available at: https://www.who.int/news-room/fact-sheets/detail/headache-disorders

[x] EMHA. 2021. Migraine in the EU – Bringing women out of the shadows. [online] Available at: https://www.emhalliance.org/wp-content/uploads/Women-M-Policy-Paper-FINAL23MARCH.pdf

About PEARL
The Pan-European Real World (PEARL) study will generate important information about real-world effectiveness of fremanezumab in adult patients with chronic migraine or episodic migraine (EM). PEARL is an ongoing, 24-month, multicentre, prospective, observational, Phase IV study.

PEARL will evaluate:

  • Effectiveness
  • Treatment adherence and persistence
  • Effectiveness in patients switching from another mAb targeting the CGRP pathway
  • Concomitant preventive and acute migraine medication use

About AJOVY (fremanezumab-vfrm) injection
AJOVY is indicated for prophylaxis of migraine in adults who have at least 4 migraine days per month. AJOVY is available as a 225 mg/1.5 mL single dose injection in a pre-filled syringe or, in some countries, in a pre-filled pen. Two dosing options are available: 225 mg once monthly administered as one subcutaneous injection (monthly dosing), or 675 mg every three months (quarterly dosing), which is administered as three subcutaneous injections.

AJOVY can be administered either by a healthcare professional or at home by a patient or caregiver. No starting dose is required to begin treatment.

Information for Europe about AJOVY can be found here.

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse events.  Information can be found at https://www.hpra.ie.

About Teva

Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) has been developing and producing medicines to improve people’s lives for more than a century. We are a global leader in generic, biosimilar and specialty medicines with a portfolio consisting of over 3,500 products in nearly every therapeutic area. Around 200 million people around the world take a Teva medicine every day and are served by one of the largest and most complex supply chains in the pharmaceutical industry. Along with our established presence in generics, we have significant innovative research and operations supporting our growing portfolio of specialty and biopharmaceutical products. Learn more at http://www.tevapharm.com

Breakthrough device for glioblastoma

Carthera receives FDA breakthrough device designation for SonoCloud-9 system, allowing for enhanced interaction with FDA and recognising SonoCloud system as innovative and promising approach for treatment of recurrent glioblastoma

Carthera, a French company that designs and develops SonoCloud, an ultrasound-based medical device to treat a wide range of brain diseases, announced on June 22 2022 that its SonoCloud-9® system has been listed as a Breakthrough Device by the Center for Devices and Radiological Health (CDRH) at the US Food and Drug Administration (FDA).


 The SonoCloud device uses low intensity pulsed ultrasound to temporarily disrupt the Blood-Brain Barrier (BBB), to allow higher brain exposure to therapeutic compounds. By using SonoCloud, the therapeutic efficacy of new and existing therapies can be unlocked and harnessed to improve the treatment of a wide range of brain diseases, such as glioblastoma.
 
“There is a significant unmet need for new treatments for glioblastoma patients, who have very few available therapeutic options,” said Michael Canney, chief scientific officer at Carthera. “We’re excited that the FDA has acknowledged the innovative potential of the SonoCloud approach through the granting of this Breakthrough Designation.”
 
The Breakthrough Devices Designation, intended to expedite the development and review of the medical device, was based on preliminary phase 1/2a clinical data that indicates substantial improvement over available second-line therapy (publication under preparation).
 
“The FDA Breakthrough Device Designation will help Carthera to efficiently advance to a pivotal trial and Premarket Approval (PMA),” said Sandra Thiollière, head of quality and regulatory affairs at Carthera. “We look forward to working closely with the FDA through this accelerated process to bring SonoCloud to patients with recurrent glioblastoma.”
 
This designation will give Carthera access to priority review, more intensive FDA interaction to build an efficient device development programme and commitment from experts and senior managers from the FDA, who will assist the company in addressing any potential challenges during the premarket review phase.

“Following the recent successful completion of our phase 1/2 trial in recurrent glioblastoma, this Breakthrough Device Designation is another important milestone supporting the potential of SonoCloud.”

Frédéric Sottilini, CEO of Carthera.

About SonoCloud-9
The SonoCloud-9 device is implanted in a skull window, below the skin; once in place it is invisible. When activated for few minutes using a transdermal needle connection to an external control unit, the BBB is disrupted for several hours; a window during which drug therapies can be administered. By administering therapies when the BBB is disrupted, drugs can reach the brain in higher and more effective concentrations. This treatment can be repeated at each cycle of drug therapy.
 
About the FDA Breakthrough Device Programme
The goal of the Breakthrough Devices Program is to provide patients and health care providers with timely access to certain medical devices by speeding up their development, assessment and review, while preserving the statutory standards for Premarket Approval, 510(k) clearance and De Novo marketing authorization, consistent with the Agency’s mission to protect and promote public health.

Study: Improvements in TBI Patients with Persistent Brain Fog

A new study has shown that plasticity-based brain training can drive improvements in patients with persistent symptoms of Traumatic Brain Injury (TBI). Gains were observed in standard measures of cognition, standard measures of self-reported symptoms, and the connectivity between brain regions. The intervention used in the study was brain exercises from BrainHQ, made by Posit Science.

Traumatic Brain Injury affects millions of Americans every year, with an estimated 2.5 million treated in emergency rooms. Most recover fully, but for some, the symptoms persist for years and disrupt earning a livelihood and personal relations. An estimated two percent of Americans live with these long-term effects.

Researchers at New York University enrolled 21 patients with chronic TBI that had persisted, on average, for more than seven years. Patients were diagnosed with mild, moderate, or severe TBI, and assigned to either an intervention group or a control group. The intervention group was asked to complete a total of 40 hours of training over 13 weeks (or about 3 hours per week). Before and after the 13-week period, cognitive function was measured with standardised neurocognitive tests, and brain connectivity was measured with fMRI brain imaging.

The researchers found that the brain training group showed significant improvements in standard cognitive tests of attention, memory, and executive function, as well as in standard measures of self-reported symptoms, as compared to the control group. Imaging revealed significant improvement in the functional connectivity across a key network of brain regions – known as the Default Mode Network (DMN). Lower connectivity is associated with cognitive dysfunction and deficits.

“This new study confirms and extends what has been seen in seven prior studies of chronic TBI and BrainHQ, which have shown study participants improved measures of cognitive abilities and symptoms, with imaging showing functional re-organization of the brain” observed Dr. Henry Mahncke, CEO of Posit Science.

These type of persistent symptoms — following not just Traumatic Brain Injuries, but other types of injuries such as “chemobrain,” “cardiobrain,” and “long COVID” — are increasingly known as “brain fog.” Researchers increasingly believe that common brain mechanisms underly the brain fog seen across these disparate conditions – which may explain the similar pattern of results seen in three studies of BrainHQ in cancer patients and seven studies in heart failure patients showing similar types of improvement.

More than 100 published studies of the exercises in BrainHQ have shown benefits, including gains in standard measures of cognition (attention, speed, memory, executive function, social cognition), in standard measures of quality of life (mood, confidence and control, managing stress, health-related quality of life) and in real world activities (gait, balance, driving, everyday cognition, maintaining independence). BrainHQ is now offered, without charge, as a benefit by leading national and 5-star Medicare Advantage plans and by hundreds of clinics, libraries, and communities. Consumers can also try BrainHQ for free at http://www.brainhq.com.

In Vitro diagnostic test for assessment of Alzheimer’s disease

The U.S. Food and Drug Administration (FDA) has granted De Novo marketing authorisation for Fujirebio Diagnostics’ Lumipulse® G β-Amyloid Ratio (1-42/1-40) in vitro diagnostic (IVD) test for the assessment of β-Amyloid pathology in patients being evaluated for Alzheimer’s disease (AD) and other causes of cognitive decline. The test, which was granted Breakthrough Device Designation by the FDA, is the first FDA-authorised in vitro diagnostic test in the U.S. to aid in the assessment of Alzheimer’s disease and other causes of cognitive decline.

Alzheimer’s disease is a leading cause of disability and death internationally, but current diagnostic methods are limited. AD develops over many years, long before symptoms are evident, but the lack of accessible diagnostics results in many patients remaining undiagnosed until the disease is well advanced, when few effective interventions remain.

A key feature of AD is the presence of β-Amyloid plaques in the brain. β-Amyloid plaques are believed to contribute to the loss of cognitive function that characterises AD, but accurately evaluating amyloid pathology has been difficult. Clinicians have relied primarily on cognitive assessments, including standardised cognitive screening tests. However, in early stages of the disease, a diagnosis of Alzheimer’s disease relying primarily on cognitive tests has been shown to be incorrect in approximately 50-60% of patients1. The Lumipulse G β-Amyloid Ratio (1-42/1-40) offers an alternative to the current standard for determining amyloid-pathology, amyloid positron emission tomography (PET) brain imaging which is expensive, subjective, time consuming, inaccessible to many Americans, and often not covered by health insurance.

The Lumipulse G β-Amyloid Ratio (1-42/1-40) test is an accurate, minimally invasive, accessible measure of β-Amyloid that can detect the formation of amyloid plaques early in the disease. It is intended for use in adult patients aged 55 years and older presenting with cognitive impairment who are being evaluated for Alzheimer’s disease and other causes of cognitive decline. The β-Amyloid Ratio test measures the concentrations of β-Amyloid 1-42 and β-Amyloid 1-40 in the CSF to calculate a numerical ratio as a proxy for the presence of β-Amyloid plaque in the brain.

“FDA authorisation of the Lumipulse G β-Amyloid Ratio (1-42/1-40) test and the upcoming U.S. launch are important milestones in the campaign to transform AD into a manageable disease,” says Monte Wiltse, President and CEO at Fujirebio Diagnostics, Inc. “Patients, physicians and families now have a valuable new tool to help identify those individuals whose early symptoms may be indicative of AD, providing the opportunity to adopt life style changes and potentially to access new therapies aimed at slowing or stopping disease progression. FDA authorisation of this first IVD biomarker test reflects our ongoing commitment to working with the healthcare community and AD advocates to achieve significant progress against this devastating disease.”

William Hu, MD, PhD is Chief, Division of Cognitive Neurology at Robert Wood Johnson Medical School and Principal Investigator of the Hu Lab, which focuses on researching fluid biomarkers for AD and other neurodegenerative disorders. Dr. Hu says, “The development of accurate tests for AD using biomarkers found in the CSF or other bodily fluids is a requirement if we are to make real progress against this dreaded disease. The importance of early diagnosis in AD is widely acknowledged, but until now, there has been no approved biomarker test available to clinicians and patients. FDA authorisation of the Fujirebio β-Amyloid Ratio test is a significant advance that marks the advent of a new era, facilitating more efficient clinical trials for new AD therapies and enabling patients and their doctors to make more informed decisions and take action much earlier in the disease process.”

The Lumipulse G β-Amyloid Ratio (1-42/1-40) test is not intended as a screening or standalone assay to diagnose AD. Results must be interpreted in conjunction with other patient clinical information. The assay is analysed on Fujirebio’s fully automated Lumipulse G1200 instrument system.

www.fujirebio.com.

References

1. Schneider, Julie A. Arvanitakis, Z. Leurgans, S.E. Bennet DA. The Neuropathology of Probable Alzheimer’s Disease and Mild Cognitive Impairment. Ann Neurol. 2009;66(2):200-208. doi:10.1002/ana.21706.

2. Gobom J, Parnetti L, Rosa-Neto P, et al. Validation of the LUMIPULSE automated immunoassay for the measurement of core AD biomarkers in cerebrospinal fluid. Clin Chem Lab Med. 2022;60(2):207-219. doi:10.1515/cclm-2021-0651.

Brain-computer interface helps paralysed patient drive again

Almost ten years ago, Aldana Zuniga was paralysed from the waist down in a car accident. Now, a microchip implanted in his brain has helped him get behind the wheel of a car again.

Using only his thoughts to control the speed, Zuniga drove laps in a NASCAR Cup racecar on a track in the US, despite the 2013 car crash leaving him with no mobility below the waist and limited use of his hands and arms.

The brain-computer interface he used was developed by a team of physicians, researchers and engineers. The team was led by neurosurgeon Scott Falci, M.D., from the Falci Institute for Spinal Cord Injuries at Colorado’s Swedish Medical Center, who also founded Falci Adaptive Motorsports in 2012 to help people with mobility impairments drive again.

The team spent over a year adapting the brain-computer interface to read Zuniga’s thoughts. A microchip electrode placed on his brain communicates with a computer in the car to control the engine.

“The electrical changes get picked up on the electrode, travel down a cable underneath his skin to a computer processor,” Falci told CBS Denver. “When the computer recognises that particular fingerprint, it knows to send the signal to the computer in our racecar, and that computer knows to send it to the throttle and to actuate the throttle.”

A specialised helmet picks up Zuniga’s head movements to steer the car, and he can exhale into or inhale from an attached tube to help control the accelerator and brakes.

The initiative was developed largely to demonstrate the ultimate potential of brain-computer interfaces.

We can use this potentially for driving an electric wheelchair, a golf cart, [to] control a robotic arm, control an exoskeleton device, control an implanted medical device,” he explained. “Once we develop that science, that science can be used for all types of systems.

Falci’s system joins others that have found success in translating thoughts into actions in the last couple of years, from an FDA-approved wireless brace that improves hand function in stroke patients to a bionic arm that restores function and feeling in amputees.

Recently, Synchron unveiled study results showing that its stent-like Stentrode system remained safely in place and functional one year after the minimally invasive implant procedure. The device has so far been implanted in a handful of patients who are paralysed due to amyotrophic lateral sclerosis, and who can use the system to send text messages and emails, shop and bank online and even send tweets, all using only their thoughts—plus an eye-tracking device to move the cursor.

Management of urinary incontinence in adults with MS or SCI

Ipsen receives positive opinion in Europe for Dysport® in the management of urinary incontinence in adults with neurogenic detrusor overactivity due to Multiple Sclerosis or Spinal Cord Injury

  • Submission based on data from the pivotal international Phase III CONTENT clinical programme, also recently published in European Urology1
  • CONTENT showed that Dysport® decreased incontinence episodes, detrusor pressure and increased bladder capacity versus placebo, and improved quality of life1

Ipsen announced on June 9th that Dysport® (abobotulinumtoxinA) has received positive opinion in Europe for the management of urinary incontinence (UI) in adults with neurogenic detrusor overactivity (NDO) due to spinal cord injury (SCI) (traumatic or non-traumatic) or multiple sclerosis (MS), who are regularly performing clean intermittent catheterisation (CIC).

This positive opinion for Dysport® now permits individual European country Health Authorities to grant national approvals, according to their country regulations. In addition, Ipsen is also currently in the process of obtaining approvals in other countries outside the European Union.

Dysport® is an injectable form of a botulinum neurotoxin type A (BoNT-A) product, which has previously shown clinically meaningful benefit in the symptomatic treatment of focal spasticity and cervical dystonia.

References

1. Kennelly M et al., Efficacy and Safety of AbobotulinumtoxinA in Patients with Neurogenic Detrusor Overactivity Incontinence Performing Regular Clean Intermittent Catheterization: Pooled Results from Two Phase 3 Randomized Studies (CONTENT1 and CONTENT2). European Urology. 2022; S0302-2838(22)01680–3
2. Mehnert U, et al., The Management of Urine Storage Dysfunction in the Neurological Patient. SN Comprehensive Clinical Medicine. 2019; 1:160–182
3. Alsulihem A and Corcos J. Evaluation, treatment, and surveillance of neurogenic detrusor overactivity in spinal cord injury patients. Neuroimmunol Neuroinflammation. 2019; 6:13
4. Ginsberg, D. The Epidemiology and Pathophysiology of Neurogenic Bladder. Am J Manag Care. 2013; 19(10)191–6

Chronic pain: discovery in the brains of army veterans could pave way for personalised treatments

Study is first to investigate the neural hallmarks of co-occurring chronic pain and trauma in veterans, finding high, medium, and low symptom groups       

Chronic pain and trauma often co-occur. However, most previous research investigated them in isolation and using subjective measures such as surveys, leading to an incomplete picture. A new study in Frontiers in Pain Research found three unique brain connectivity signatures that appear to indicate veteran susceptibility or resilience to pain and trauma, regardless of their diagnostic or combat history. The study could pave the way for more objective measurements of pain and trauma, leading to targeted and personalised treatments.

Chronic pain and trauma are linked but not studied together

“Chronic pain is a major public health concern, especially among veterans,” said first author Prof Irina Strigo of the San Francisco Veterans Affairs Health Care Center, US. “Moreover, chronic pain sufferers almost never present with a single disorder but often with multiple co-morbidities, such as trauma, posttraumatic stress, and depression.”

Researchers already understand that both pain and trauma can affect connections in our brains, but no-one had studied this in the context of co-occurring trauma and pain. Much pain and trauma research also relies on subjective measurements, such as questionnaires, rather than objective measurements, such as brain scans.

Identifying brain connectivity signatures of pain and trauma

Taking a different approach, the researchers behind this new research studied a group of 57 veterans with both chronic back pain and trauma. The group had quite varied symptoms in terms of pain and trauma severity. By scanning the veterans’ brains using functional magnetic resonance imaging, the researchers identified the strength of connections between brain regions involved in pain and trauma. They then used a statistical technique to automatically group the veterans based on their brain connection signatures, regardless of their self-reported pain and trauma levels.

Based on the veterans’ brain activity, the computer automatically divided them into three groups. Strikingly, these divisions were comparable to the severity of the veterans’ symptoms, and they fell into a low, medium, or high symptom group.

The researchers hypothesised that the pattern of brain connections found in the low symptom group allowed veterans to avoid some of the emotional fallout from pain and trauma, and also included natural pain reduction capabilities. Conversely, the high symptom group demonstrated brain connection patterns that may have increased their chances of anxiety and catastrophising when experiencing pain.

Interestingly, based on self-reported pain and trauma symptoms, the medium symptom group was largely similar to the low symptom group. However, the medium symptom group showed differences in their brain connectivity signature, which suggested that they were better at focusing on other things when experiencing pain, reducing its impact.  

Putting the findings into future practice

“Despite the fact that the majority of subjects within each subgroup had a co-morbid diagnosis of pain and trauma, their brain connections differed,” said Strigo.

“In other words, despite demographic and diagnostic similarities, we found neurobiologically distinct groups with different mechanisms for managing pain and trauma. Neurobiological-based subgroups can provide insights into how these individuals will respond to brain stimulation and psychopharmacological treatments.”

So far, the researchers don’t know whether the neural hallmarks they found represent a vulnerability to trauma and pain or a consequence of these conditions. However, the technique is interesting, as it provides an objective and unbiased hallmark of pain and trauma susceptibility or resilience. It does not rely on subjective measures such as the surveys. In fact, subjective measurements of pain in this study would not differentiate between the low and medium groups.

Techniques that use objective measures, such as brain connectivity, appear more sensitive and could provide a clearer overall picture of someone’s resilience or susceptibility to pain and trauma, thereby guiding personalised treatment and paving the way for new treatments.

Despite demographic and diagnostic similarities, we found neurobiologically distinct groups with different mechanisms for managing pain and trauma. Neurobiological-based subgroups can provide insights into how these individuals will respond to brain stimulation and psychopharmacological treatments.

Prof Irina Strigo, San Francisco Veterans Affairs Health Care Center, US

NICE Assessment for SPRAVATO®▼

Janssen was disappointed with the recent decision (27/5/22) by the National Institute for Health and Care Excellence (NICE) on their Final Appraisal Determination, in which SPRAVATO®(esketamine) nasal spray has not been recommended for use within its marketing authorisation, in combination with a selective serotonin reuptake inhibitor (SSRI) or serotonin and norepinephrine reuptake inhibitor (SNRI), for adults living with treatment-resistant major depressive disorder (TRD), who have not responded to at least two different treatments with antidepressants in the current moderate to severe depressive episode.

  • Esketamine nasal spray is the first antidepressant with a new mechanism of action in more than 30 years
  • Esketamine nasal spray was authorised for the treatment of adults with treatment-resistant major depressive disorder in Europe in December 2019
  • Its novel mechanism of action means it works differently than currently available therapies for major depressive disorder. Esketamine nasal spray is derived from part of the ketamine molecule but is appraised by health authorities as a distinct medication, due to differences in the efficacy and safety profile. As such, it is important these terms are not used interchangeably

We have worked hard with NICE and other stakeholders throughout the appraisal process to provide the clinical evidence and data to demonstrate esketamine nasal spray is a cost-effective treatment for use on the NHS. Therefore, we are deeply disappointed with the decision published by NICE,” commented Amanda Cunnington, Senior Director of Patient Access, Janssen-Cilag Limited. “In treatment-resistant major depressive disorder, there continues to be systemic issues in introducing innovative treatment options on the NHS, which we have tried to overcome. We remain steadfast in collaborating with stakeholders and are considering all options including an appeal, to enable access to this important treatment for people living with the condition.”

For the last thirty years we have been waiting for innovations in the field for the most serious and debilitating mental illnesses such as treatment-resistant major depressive disorder,” commented Marjorie Wallace, Chief Executive, SANE. “It is, therefore, a huge disappointment that NICE’s decision will prevent the most desperate patients from accessing esketamine nasal spray.

We have little in our armoury to combat treatment-resistant major depressive disorder and the real shame is that NICE are rejecting one of the very few innovations in treating this condition.

Marjorie Wallace, Chief Executive, SANE