The Axon – Issue #5, August 2024
Welcome to The Axon! If this is your first time here, thanks for joining us! If you're a repeat reader of NeurologyLive? or this newsletter, welcome back!
If you're part of the latter group, go ahead and scroll down a bit to get right into the updates. But for those of the former group, we're a team of editors for a clinical news publication that provides the latest coverage of neurology-related FDA news and the therapeutic pipeline, expert opinions and insights, in-clinic care and advocacy, and major medical meetings throughout the year. Our mission is to deliver?quality and relevant information to?health care professionals treating neurological diseases to help them achieve the best patient care possible. This newsletter is The Axon, your new go-to place to get that insight, right here on LinkedIn.
On the first of each month, we'll bring you a new edition to highlight the trending topics and important updates our editorial staff reports on. We'll point you to the news that matters and the specialist insight that can help your clinical practice.
Without further ado, let's get into what happened this past month!
FDA Actions
We were busy following the US regulator's actions this past month, which included the clearance of an investigational new drug application for Indapta Therapeutics’ g-natural killer cell therapy IDP-023 to be assessed in a phase 1 clinical trial of patients with progressive multiple sclerosis, an area of clear therapeutic need in MS (and one that has emerged as a candidate for cell-based therapies). Mark Frohlich, MD, the CEO of Indapta, told us that the company is "very encouraged" by the acceptance, adding that "there is a high unmet need for these patients, with ocrelizumab (Ocrevus; Roche) being the only FDA-approved therapy for patients with primary progressive MS," and adding that “G-NK cells in combination with ocrelizumab have the potential to eliminate the autoreactive T and B cells that are responsible for the disease."
Additionally, the FDA gave the long-awaited go-ahead to Amneal Pharmaceuticals’ agent IPX203 (now marketed as Crexont), an oral formulation of carbidopa/levodopa extended-release capsules, as a treatment for patients with Parkinson disease (PD). The treatment had a somewhat bumpy ride to get to this point, with its new drug application (first submitted to the agency back in November 2022) receiving a complete response letter in July 2023. But after it was resubmitted earlier this year after additional information from a healthy volunteer study, the agency's concerns seem to have been addressed. In the days following the approval, we brought together PD experts Robert Hauser, MD, of the University of South Florida, and Hubert Fernandez, MD, of Cleveland Clinic, to discuss the approval and its implications in depth in our Special Reports series.
You can check out that whole 5-part series here: Special Report: IPX203 as New Treatment for Parkinson Disease; but you can also catch a peek of Episode 1 below:
Outside of the FDA, we did see some movement across the pond in the European Union, where the European Medicines Agency (EMA) announced in early August that it had adopted a negative opinion for the approval of lecanemab (Leqembi) as a treatment for patients with early-stage Alzheimer disease (AD). Eisai Co., Ltd. announced in response that it plans to re-examine the CHMP opinion and work swiftly with the parties involved to ensure the treatment becomes available. Later in the month, the United Kingdom’s Medicines and Healthcare products Regulatory Agency (MHRA) approved the treatment, but the NICE - National Institute for Health and Care Excellence denied access to the treatment through the National Health Service (NHS), which many advocacy groups, such as the Alzheimer's Association?, noted could negatively impact global health inequity. This marks just another complicated step in the already very bumpy road that has become the progression of these AD monoclonal antibodies from clinical development to clinical care.
Hot Topics in Multiple Sclerosis
A major theme that emerged from our coverage in August was the ongoing conversations in multiple sclerosis (MS) that are top of mind for clinicians. As is the rest of the field, we're eagerly awaiting the presentation of the new 2023 updates to the McDonald criteria at the upcoming ECTRIMS 2024 Congress (which we'll be attending in Copenhagen!), but in the meantime, we've had some pretty intriguing conversations with experts in clinical care.
The first of those topics was around MS and domestic violence and abuse, which was a topic of the 2023 Herndon Award-winning article that detailed a tool to ascertain abuse and neglect in adults with MS, called STRESS-MS, that was found reasonably reliable and valid for detecting caregiver mistreatment. Our colleagues at the International Journal of MS Care (IJMSC) brought together a couple of experts to discuss the topic: Suzanne Britt, MSc, BMedSci, BA, RM; and Elizabeth Morrison-Banks, MD, MSEd (one of the authors of the aforementioned paper). The conversation is compelling and full of depth and nuance—they cover everything from having hard conversations about it, managing caregiver and patient stress, and which stakeholders to involve in these situations. I highly suggest checking out both parts:
The team also put together a second Special Reports series this month, this time focusing on the sphingosine 1-phosphate (S1P) receptor modulator class—a newish drug class in MS that has emerged as a disease-modifying option with a unique mechanism of action compared with other therapies. To date, 4 S1P receptor modulators: fingolimod (Gilenya; Novartis ), ozanimod (Zeposia; Bristol Myers Squibb), ponesimod (Ponvory; Janssen Inc.), and Siponimod (Mayzent; Novartis), are approved by the FDA and the European Medicines Agency for the treatment of MS. In our 6-part series, experts Patricia Coyle, MD, FAAN, of Stony Brook University, and Adnan Subei, DO, FAAN, of Neurology Consultants of Dallas, covered the long-term impacts of S1P-modulating treatments for MS, the differences in each treatment, and how the class has evolved since the first therapeutic over 10 years ago.
You can check out that whole series, which features some great insight into how these therapies fit into the paradigm and the future of the class's use in the clinic, here: Multimodal Actions of S1P Receptor Modulators in Multiple Sclerosis.
The final conversation we had this month in MS was about a novel tool called the DAAE score, a tool that was recently assessed in work published in Multiple Sclerosis and Related Disorders by Tom Fuchs, MD, PhD, of Amsterdam UMC, and colleagues. The score estimated patient risk to transition to secondary progressive MS consistently across international datasets over a 5-year period, with results suggesting that the DAAE score is an easy-to-use tool; however, it may need additional validation in larger cohorts to be used for clinical risk estimation in MS. We spoke directly with Fuchs about how it was developed:
Fuchs also provided an excellent explanation of the tool's purpose—in his own words, it was built to support personalized multiple sclerosis care and address the question, “How likely is it that my patient’s disease will worsen in the years ahead?” This sort of predictive tool opens conversations between patients and their doctors about goals of care, wishes for the future, and the desired path forward in balance with known risks.
Read Fuch's explanation of the tool here: Personalized Medicine: Predicting the Transition to Secondary Progressive Multiple Sclerosis
Applying New Tools and Technologies
In that same vein, we're constantly having conversations about new technologies that are being tested and applied in clinics around the world. Similar to the newly developed DAAE score, we spoke with @Linda Papa, MD, MSc, CCFP, FRCP(C), FACEP, of Orlando Health, about the i-STAT traumatic brain injury (TBI) cartridge test, which was approved in April of this year for the assessment of patients with suspected mild TBIs, known as concussions, at their bedside. Orlando Health was the first hospital system in the world to utilize the test, so we connected with Papa—who also helped assist in pioneering it—to find out just how helpful it could be.
She told us that it seems to be as effective as hoped, providing results to clinicians in approximately 15 minutes. Papa said, "when we first started doing this research about 25 years ago, our vision was to have a tool, like a glucometer when people measure their blood glucose, to be able to tell us what was going on in the brain, give us an idea." However, the test is not perfect, and Papa also detailed the challenges involved in adapting it for use in pediatric and older patients.
领英推荐
Technology advances like that have shown great promise and put some serious creative thinking on display in the past several years. One such example of the rapid use of new tech has been the application of virtual reality (VR) in neurological care. This month, Abraham Homer, MS, of Children's Hospital Colorado, highlighted the use of VR in smoothing out the blood draw process for patients with spinal muscular atrophy. As Homer points out, blood draws are more than just a minor inconvenience to these children—SMA weakens the muscles, making it difficult to find veins, and the fear of pain or discomfort can heighten anxiety, making the procedure even more challenging. Additionally, repeated draws can become psychologically distressing. The need to help was apparent, and it seems that VR might offer some relief to make this process less stressful for patients.
Read Homer's piece on how it has worked for his group: Virtual Reality is a Game-Changer During Blood Draws for Pediatric Patients With Spinal Muscular Atrophy
And, once again, our recurring column from Neal K. Shah, highlighted another cool way tech, specifically AI, is being implemented in the realm of chronic pain. As he points out, music therapy has proven to be a fairly versatile intervention in addressing the factors that exacerbate chronic pain. It can be used in part to reduce pain intensity, divert attention from pain, alleviate stress and anxiety, and enhance mood. The effectiveness of music therapy stems from its engagement of the brain's reward system—functional MRI studies have shown that preferred music listening activates the nucleus accumbens, which was associated with a 21% reduction in reported pain intensity in some patients with chronic pain conditions. As for applicability, as Shah puts it: "music therapy is often employed in diverse contexts, from procedural pain relief to end-of-life care."
Read Shah's latest: Exploring AI-Powered Music Therapy as a Solution to Chronic Pain Management and the Opioid Crisis
Mind Moments
Worth highlighting this month were the 2 episodes of our podcast, Mind Moments, that went live this month (you can catch new shows every other Friday on your favorite podcast service). Both featured some interesting conversations on therapeutics in development and were definitely timely!
The first featured Phil Jochelson, MD, of Jazz Pharmaceuticals, who discussed the phase 4 XYLO study evaluating the effects of switching from high-sodium to low-sodium oxybate on blood pressure in patients with narcolepsy. He gave some insight regarding the conduct of the trial, including end points, objectives, and patient demographics, as well as some of the benefits to studying blood pressure and cardiovascular risks. In addition, he discussed enhancements to narcolepsy care through low-sodium oxybate, the importance of unique studies like XYLO, and the need to educate clinicians on sodium load and its risks.
You can check out that episode here:
The second of those episodes featured Sharon Cohen, MD, of the University of Toronto, who spoke with us about the recent positive data from an ongoing phase 1 study of mivelsiran (Alnylam Pharmaceuticals), the first investigational RNA interference therapeutic targeting amyloid precursor protein for AD. Cohen also touched on how RNA therapeutics could be used in combination with previously approved novel treatments and the benefits mivelsiran brings with no observed amyloid-related imaging abnormalities. Furthermore, the discussion covered some of the potential of this investigational agent, what to expect in the multi-dose part B of the study, and an additional phase 2 study in cerebral amyloid angiopathy.
You can check out that episode here:
Newborn Screening
Although Newborn Screening Awareness Month isn't celebrated until now (September), August was SMA Awareness Month, and those 2 topics are extremely intertwined. Toward the end of the month, we caught up with Crystal Proud, MD, of the Children's Hospital of The King's Daughters, to discuss aspects of awareness for SMA that have improved over the years—particularly in newborn screening. This conversation was coincidentally very timely, as it came within a few days of Massachusetts becoming thee most recent state to add SMA to its newborn screening panel. The identification of SMA is critical in terms of improving patient outcomes and prognosis. As Proud put it, "the goal [is] to treat as soon as possible...every day that a child with SMA goes untreated is a day where we could potentially be losing very valuable motor neurons."
In addition to summarizing the progress made, she stressed the continued efforts needed to enhance the screening process, and pivotal research initiatives going forward. speaking on some of the inconsistencies with the post-screening process and the ways to efficiently ensure access to novel, disease-modifying treatments.
Alzheimer's Association International Conference
Finally, the annual Alzheimer's Association? International Conference, which was held in Philadelphia, Pennsylvania, technically ended in early August, and our team was on the ground talking with presenting authors and thought leaders that whole week. Our coverage has continued into this month, with some really good conversations showing up on our website.
You can check out all of our coverage here: AAIC 2024, but I've also highlighted and linked to some of the excellent dialogue we shared with experts from the meeting below:
That wraps up this month's issue of The Axon—thanks for reading! Remember to subscribe to get alerts each time a new issue goes live!
Do you have a lead on a story you want to share? Let us know—email Matt Hoffman, our editorial director, at [email protected].
We'll see you here next month!