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Neurology News Network. for the week ending February 23, 2025. [WATCH TIME: 3 minutes]

Harmony Receives RTF Letter for Pitolisant, FDA Accepts Vatiquinone NDA, Gene Therapy SGT-003 Performs Well in Phase 1/2 Trial

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Take 5 minutes to catch up on NeurologyLive®'s highlights from the week ending February 21, 2025. 

NeurologyLive® Friday 5 — February 21, 2025

The president of the American Heart Association discussed how precision medicine, advanced imaging, and expanded treatment windows are transforming stroke care, as displayed at ISC 2025. [WATCH TIME: 5 minutes]

Innovation in Stroke Care and Expanding the Treatment Windows: Keith Churchwell, MD, FAHA, FACC, FACP

Pathogenic variants in the CACNA1A, ATP1A2, and SCN1A genes were associated with a higher risk of migraine, particularly in heterozygous carriers of loss-of-function and neutral variants.

High-Risk Genes for Familial Hemiplegic Migraine Do Not Elevate Epilepsy Risk, Study Shows

Attending Physician, Neuromuscular/General Neurology & Electromyography; Neuromuscular Education Director and Neuromuscular Section Head, Children’s Hospital of Philadelphia

The pediatric neurologist at Children’s Hospital of Philadelphia provided background on a notable track session at the upcoming MDA Clinical & Scientific Conference covering updates in gene therapy for neuromuscular conditions. [WATCH TIME: 4 minutes]

Navigating the Future of Gene Therapy in Neuromuscular Disorders: John Brandsema, MD

Marco Meglio, Assistant Managing Editor for 

, has been with the team since October 2019. Follow him on Twitter 

A pair of lead neurologists at Baptist Health South Florida provided commentary on some of the promising developments expected to emerge in neurology over the coming months.

Exciting Innovations in Neurology to Come in 2025: Insights From Baptist Health

The assistant professor in the neurology department at the University of Utah in Salt Lake City discussed the importance of addressing broader quality-of-life measures in patients with NMOSD beyond just preventing relapses. [WATCH TIME: 3 minutes]

Managing NMOSD Disease Progression Through Healthy Habits and Holistic Care: Tammy Smith, MD, PhD

NeurologyLive is your direct connection to the latest neurology news and interviews with expert neurologists in multimedia formats.

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Panelist discusses how bladder dysfunction in neurological conditions requires attention, as it significantly affects patient quality of life and can indicate disease progression or complications. Neurologists face challenges in diagnosis and treatment due to overlapping symptoms, complex neural pathways involved, and the need to differentiate between multiple potential causes.

Neurogenic Bladder: Challenges in Diagnosis

Panelist discusses how the neuroanatomy of bladder function involves a sophisticated interplay between autonomic and somatic nervous systems. The bladder is controlled by parasympathetic nerves (S2-S4) for detrusor contraction, sympathetic nerves (T11-L2) for sphincter control, and somatic nerves for voluntary control via the pudendal nerve. This complex coordination enables both automatic storage and voluntary voiding through reciprocal innervation.

Lower Urinary Tract Overview

Tamara Kaplan, MD, introduces a new video series highlighting the scope and treatment of neurogenic bladder.

Addressing Neurogenic Bladder: Understanding Prevalence, Unmet Needs, and Effective Management

According to a new announcement, the FDA has approved suzetrigine (Vertex Pharmaceuticals), an oral selective NaV1.8 pain signal inhibitor, to treat patients who experience moderate-to-severe acute pain. Marketed as Journavx, the novel, non-opioid therapy becomes the first new class of medicine to treat acute pain in over 20 years.

The new drug application (NDA) for suzetrigine, formally known as VX-548, was based on data from a phase 3 program that included 2 randomized, double-blind, placebo-controlled trials; 1 post abdominoplasty surgery and 1 post bunionectomy surgery. The program also included a single arm safety and efficacy study that included patients with a wide range of surgical and non-surgical pain conditions.

"This is the first new and nonopioid pain class we've had at our disposal in over 20 years. It provides a selective, nonaddictive alternative to opioids for treatment of moderate to severe acute pain," Jessica Oswald, MD, MPH, steering committee member at Vertex and associate professor in pain management and emergency medicine at UC San Diego, told 

in a recent interview. "This offers an effective alternative to opioids, and it expands our nonopioid armamentarium. In the emergency department, I'm frequently stuck. I have patients with acute pain, and I have opioids, and I have to get creative with some of our available options. So this really provides one additional medication that I can use in my toolbox." 

Suzetrigine, which previously received breakthrough therapy, fast track, and priority review designations by the FDA, is contraindicated for concomitant use with strong CYP3A inhibitors. Additionally, patients should avoid food or drink containing grapefruit when taking the medication. 

"I think it will reduce a reliance on opioids, particularly in the perioperative and acute pain setting. I think NaV receptors are here to stay. I think suzetrigine, having its availability, will accelerate research into NaV inhibitors, and I think we're going to potentially see expanded applications for even potentially chronic pain," Oswald said. "Suzetrigine really highlights the importance of targeting peripheral receptors and potentially shifting future drug development strategies from more central acting drugs to the peripheral medications."

In the pivotal studies, suzetrigine met its primary end point of the time-weighted sum of the pain intensity difference from 0 to 48 hours, and demonstrated a clinically meaningful reduction in pain from baseline at 48 hours on the Numeric Pain Rating Scale (NPRS) after both abdominoplasty and bunionectomy surgeries. Compared with placebo, the mean difference in pain intensity from 0 to 48 hours for abdominoplasty was 48.4, and 29.3 for bunionectomy, showcasing a statistically significant improvement.

Among the patients in the single arm safety and efficacy study, 83.2% rated suzetrigine as good, very good, or excellent in treating pain based on the Patient Global Assessment (PGA) scale.

"I think the biggest studies are going to be your phase 3, NAVIGATE 1 and NAVIGATE 2 trials, which studied post-op abdominoplasty and bunionectomy. The NAVIGATE 1 and NAVIGATE 2 trials found that suzetrigine was superior to placebo for pain relief over 48 hours. It had comparable efficacy to opioids but not superior in all measures," Oswald said. "It had faster pain relief than placebo, with a median time being 2 hours, at a lower incidence of nausea, constipation and dizziness compared with opioids, and it was generally well tolerated, with no reports of respiratory depression or sedation. There was a real world study evaluating surgical and nonsurgical acute pain conditions and 83% of patients rated pain relief as 'good', 'very good' or 'excellent'."

All 3 studies revealed that suzetrigine was safe and well tolerated by participants, with majority of adverse events (AEs) being reported as mild-to-moderate. Findings from the 2 randomized controlled trials demonstrated that following abdominoplasty, 50% of patients who received suzetrigine experienced AEs, compared with 56.3% in the placebo group. After bunionectomy, 31% of patients who received the therapy reported adverse events, compared with 35.2% in the placebo group. Overall, the most common AEs observed in study participants on suzetrigine were itching, muscle spasms, increased blood level of creatine phosphokinase, and rash. 

"The common adverse events noted were headache, nausea and constipation. The company deemed these adverse events as generally mild to moderate in nature. There are no opioid related concerns. Notably, there is no respirator depression or sedation reported," Oswald added. "For monitoring considerations, I think hepatic or renal impairment patients may need additional consideration, though there was no major safety signals identified in the studies. I can see this being used as monotherapy or part of an opioid sparing strategy. I can see Suzette regime being ideal for opioid naive patients or those at risk for opioid related [adverse] effects."

An poster presented at ANESTHESIOLOGY 2024, the annual meeting of the American Society of Anesthesiologists, held October 18-22 in Philadelphia, Pennsylvania, demonstrated suzetrigine's positive effect across phase 3 clinical trial abdominoplasty and bunionectomy trials, underscoring the drug’s efficacy and safety across various pain conditions and settings. In these trials, 1118 participants underwent abdominoplasty, and 1073 participants underwent bunionectomy. All participants were aged between 18 and 80 years.

Participants who rated 4 or higher on the NPRS following surgery were randomized in a 2:2:1 ratio to receive either suzetrigine, hydrocodone bitartrate/acetaminophen (HB/APAP), or a placebo. The primary end point was the time-weighted sum of the pain intensity difference (SPID48) calculated from NPRS scores over 48 hours. A higher SPID48 value indicated a greater reduction in pain compared with baseline. Key secondary end points included the SPID48 for suzetrigine compared with HB/APAP, and the time required for suzetrigine to achieve a 2-point or greater reduction in NPRS compared to placebo. Safety was also assessed as a secondary end point.

Results showed that suzetrigine treatment significantly reduced pain compared with placebo. In the abdominoplasty trial, the least squares (LS) mean difference in SPID48 between suzetrigine and placebo was 48.4% (95% CI: 33.6, 63.1; 

 < .001). In the bunionectomy trial, the LS mean difference was 29.3% (95% CI: 14.0, 44.6; 

Neither trial demonstrated that suzetrigine was superior to HB/APAP in terms of SPID48. However, suzetrigine did exhibit a more rapid onset of meaningful pain relief than placebo in both trials. Additional findings demonstrated that the median time to achieve a 2-point or greater reduction in NPRS from baseline was significantly shorter with suzetrigine (119 minutes in the abdominoplasty trial and 240 minutes in the bunionectomy trial) compared with placebo (480 minutes in both trials; 

Suzetrigine was generally safe and well-tolerated in both trials, with AEs consistent with the post-surgical settings. The overall incidence of AEs was lower with suzetrigine compared with placebo or HB/APAP. Following abdominoplasty, the incidence of participants with any AEs was 50.0% with suzetrigine, 56.3% with placebo, and 60.7% with HB/APAP. Following bunionectomy, the rates were 31.0%, 35.2%, and 41.8%, respectively. No serious adverse events were related to suzetrigine.

In another poster presented at ANESTHESIOLOGY 2024, investigators conducted a phase 3, single-arm study to assess the safety and efficacy of suzetrigine for moderate-to-severe acute pain in a broader patient population.

 This patient population included both postoperative surgical patients and non-surgical patients with painful medical conditions. The study enrolled adults aged 18 to 80 with pain rated 4 or higher on the NPRS following surgery or presenting to a medical facility with newly developed moderate-to-severe acute pain within the past 48 hours. Participants received suzetrigine for 14 days or until pain resolved.

The primary objective was to assess safety and the secondary objective was to investigate the efficacy of suzetrigine in treating acute pain at the end of treatment as assessed by a patient global assessment. A total of 256 participants (222 surgical, 34 non-surgical) received suzetrigine. The most common surgical procedures were orthopedic, plastic and otorhinolaryngologic. The most common non-surgical conditions were sprains and strains of the upper and lower extremities.

Overall, in this second presented poster, suzetrigine was generally safe and well-tolerated in both surgical and non-surgical patients. Most AEs were reported as mild or moderate in severity, with headache being reported as the most common, occurring in 7% of participants. No serious AEs were related to suzetrigine, as noted by researchers. Majority of participants (83.2%) rated the efficacy of suzetrigine for treating pain as good, very good, or excellent at the end of the treatment period.

, researchers observed that suzetrigine reduced acute pain over a 48-hour period after abdominoplasty or bunionectomy with mild-to-moderate AEs at the highest dose. This previous trial was performed as 2 phase 2, randomized, double-blind, placebo-controlled studies. Participants included were aged between 18 years and 75 years with a pain score of at least 4 on the NPRS. Pain was also rated as moderate or severe on the Verbal Categorical Rating Scale in 4 hours after completion of the surgery and general anesthesia for those who underwent abdominoplasty and in 9 hours after removal of popliteal sciatic nerve block on postoperative day 1 in the bunionectomy trial.

For the abdominoplasty trial, 303 patients were included, with 81.5% who completed the treatment period. In the bunionectomy trial, 274 patients were included and 90.1% completed the treatment. The least-squares mean difference for the high-dose group and placebo group was 37.8 for participants in the abdominoplasty trial and 36.8 in the bunionectomy trial. For both studies, patients who received the lower doses displayed similar results as the placebo. Overall, investigators reported that headache and constipation were the most common adverse events reported with suzetrigine in this study.

"I think suzetrigine is a game changer in acute pain management. It's the first NaV 1.8 inhibitor we have available. It's the first NaV inhibitor we have available. It redefines a standard of care about providing nonopioid pain relief with fewer [adverse] effects. There are potential future applications in chronic pain, although more research is needed. It encourages a shift toward targeted, precision based pain treatment strategies, and its adoption in the clinical practice will be key to maximizing impact and reducing opioid prescribing," Oswald concluded in the interview. 

REFERENCES
1. FDA Approves Novel Non-Opioid Treatment for Moderate to Severe Acute Pain. FDA. Published January 30, 2025. Accessed January 30 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-novel-non-opioid-treatment-moderate-severe-acute-pain
2. Vertex Announces FDA Acceptance of New Drug Application for Suzetrigine for the Treatment of Moderate-to-Severe Acute Pain. News Release. Vertex. July 30, 2024. Accessed January 30 2025. https://news.vrtx.com/news-releases/news-release-details/vertex-announces-fda-acceptance-new-drug-application-suzetrigine
3. Vertex Announces Positive Results From the VX-548 Phase 3 Program for the Treatment of Moderate-to-Severe Acute Pain. News Release. Vertex. January 30, 2024. Accessed January 30 2025. https://news.vrtx.com/news-releases/news-release-details/vertex-announces-positive-results-vx-548-phase-3-program
4. Bertoch T, D’Aunno D, McCoun J, et al. Randomized, placebo-controlled, phase 3 trials of suzetrigine, a non-opioid, pain signal inhibitor for treatment of acute pain after abdominoplasty or bunionectomy. Presented at American Society of Anesthesiologists 2024 Annual Meeting; October 18-22, 2024; Philadelphia, PA. Poster A1187.
5. McCoun J, Winkle P, Solanki D, et al. A phase 3, single-arm study of suzetrigine, a non-opioid, pain signal inhibitor for treatment of acute non-surgical conditions. Presented at American Society of Anesthesiologists 2024 Annual Meeting; October 18-22, 2024; Philadelphia, PA. Poster A2074.
6.Jones J, Correll DJ, Lechner SM, et al. Selective Inhibition of Na

. 2023;389(5):393-405. doi:10.1056/NEJMoa2209870

The FDA has approved suzetrigine, an oral selective NaV1.8 pain signal inhibitor, for moderate-to-severe acute pain, marking the first new class of non-opioid analgesics in over two decades. Clinical trials demonstrated its efficacy and safety, with significant pain reduction compared to placebo in abdominoplasty and bunionectomy surgeries. Suzetrigine showed a rapid onset of pain relief and was well-tolerated, with mild-to-moderate adverse events. It offers a promising alternative to opioids, addressing public health concerns related to opioid use in pain management.

Suzetrigine, a selective inhibitor of the NaV1.8 sodium channel, offers an alternative opioid treatment option for patients to treat moderate to severe pain without risk of addiction.

Clinical

FDA Approves Vertex Pharmaceuticals' Suzetrigine for Acute Pain Management

 identified specific cerebrospinal fluid (CSF) lipids that distinguished multiple sclerosis (MS) from neuromyelitis optica spectrum disorder (NMOSD) and other neurological diseases with high accuracy, offering potential new biomarkers for diagnosis and disease monitoring. The research also reported correlations between CSF lipid levels and measures of disease activity, including Expanded Disability Status Scale (EDSS) scores and inflammatory cytokines.

In the study, researchers screened 353 lipid species in pooled CSF samples, quantifying 161 lipids across patients diagnosed with MS and NMOSD by clinical criteria as well as other inflammatory neurological diseases (OIND), and non-inflammatory neurological diseases (NIND). Significant differences emerged in the results, particularly in NMOSD, where 29 lipids—including sphingolipids and polyunsaturated lysophosphatidylcholines (LPCs)—were significantly elevated compared with MS.

"My understanding, from speaking to neuroimmunology specialists, is that diagnosis of AQP4 antibody-positive NMOSD is relatively clear-cut. The benefit of an alternative diagnosis will be distinguishing NMOSD from MS for AQP4 antibody-negative NMOSD, which I believe is somewhere in the range of 20-40% of NMOSD cases," senior author Anthony Don, PhD, a professor of medical biochemistry at the University of Sydney School of Medical Sciences, told 

in a recent interview. "We achieved very good differentiation of NMOSD from MS based on levels of just 3 lipids, and these lipids are easy to quantify with mass spectrometry systems that are used in clinical diagnostic labs. So an assay based on CSF or serum lipids would be quite easy to adapt for clinical practice, and low cost."

Further analysis showed that NMOSD cases exhibited higher levels of specific lipid classes, such as dihexosylceramides (Hex2Cer) and sphingomyelins (SM), compared with MS and NIND. A subset of OIND cases, including conditions like neurosarcoidosis and CNS lymphoma, also had elevated lipid levels similar with NMOSD. A machine-learning approach using partial least squares discriminant analysis and random forest analysis revealed that a combination of 3 lipids—GM3(d42:2), Hex2Cer(d18:1/22:0), and GM3(d38:1)—achieved 91% sensitivity and 91% specificity in differentiating NMOSD from MS. Notably, Hex2Cer(d18:1/22:0) alone distinguished NMOSD from MS with 73% sensitivity and 100% specificity at a threshold of 1.1 nmol/L CSF.

Dubai Study Highlights Disease Characteristics and Treatment Outcomes in NMOSD and MOGAD

Beyond diagnostic potential, the study examined how CSF lipids correlated with inflammatory cytokines and measures of disease activity. Several sphingolipids and LPC species were positively associated with inflammatory markers, including macrophage migration inhibitory factor (MIF), interleukin-6, and CXCL13, a chemokine involved in B-cell recruitment. Notably, 94 lipids were significantly correlated with MIF levels, with the strongest associations observed in SMs, Hex2Cers, and LPCs. Although MIF was elevated in NMOSD, it was also higher in patients with MS experiencing relapse compared with those in remission.

"Prior studies have not really looked at associations of lipid levels with inflammatory cytokines. We did this to determine if the increased levels of lipids in the CSF of [patients] with NMOSD reflect some kind of inflammatory signature and I was surprised by how strongly levels of many lipids in the CSF were correlated with the cytokine MIF. MIF is higher in [pateints] with NMOSD compared [with] MS or control [participants], so the correlation makes sense," Don explained. 

"Sphingolipid levels were higher in the CSF of [patients] with NMOSD but not MS (in fact they were higher in NMOSD compared [with] MS), so I’m not sure that CSF sphingolipids would be useful biomarkers for MS," Don added. "I think the finding of high levels of sphingolipids in the CSF of [patients] with NMOSD is clinically-relevant and should be explored as a biomarker of treatment response for that disease. Sphingolipids in the serum may be more poignant for MS and that will be discussed in a forthcoming paper."

In MS, gadolinium-enhancing (Gd+) lesions indicated active inflammation and blood-brain barrier disruption. In the study, 39 lipids, primarily phosphatidylcholine, triglycerides, and cholesterol esters (CEs), were significantly reduced in the CSF of patients with MS who had Gd+ lesions compared with those without. Notably, EDSS scores were inversely correlated with certain cholesterol esters, particularly CE(16:0), CE(22:5), and CE(22:6). Despite this correlation, the overall mean levels of these lipids did not significantly differ between disease groups.

"There is no obvious explanation for the inverse correlation between EDSS and CE(16:0), however we saw the association in 2 independent sample sets. Myelin is a vast reservoir of cholesterol, which cannot be broken down by the macrophages and microglia that degrade myelin in MS. Instead, they store the excess cholesterol that is released from the degraded myelin in the form of cholesterol esters," Don said. "Lower cholesterol ester levels in association with higher EDSS could reflect reduced cholesterol efflux from myelin plaques into the CSF as the disease progresses and plaques become chronic, or perhaps increased efflux across a leaky CSF-blood barrier. To determine if this correlation is relevant for monitoring treatment response, we would need to determine how CSF cholesterol ester levels vary over time and as a function of therapeutic response." 

Despite the study providing compelling set evidence that CSF lipids could serve as biomarkers for NMOSD and MS, authors acknowledged that several limitations exist. Researchers noted that the NMOSD sample size was relatively small, which prevented further stratification based on AQP4 antibody status. Additionally, the study did not include progressive MS cases, leaving questions about whether lipid differences extend beyond relapsing-remitting MS. Investigators also highlighted that the lack of healthy controls also meant that normal CSF lipid ranges could not be established.

All told, the current study underscored the potential of CSF lipids as biomarkers for differentiating NMOSD from MS and tracking disease activity. By identifying lipid profiles associated with inflammation and disability, these findings could pave the way for improved diagnostic and monitoring tools in neuroinflammatory diseases. Authors recommended that future research should validate these findings in larger cohorts and investigate whether lipid changes correlate with MRI measures of demyelination and therapeutic response.

"I think it is too early to talk about translation of CE(16:0) as a biomarker for MS. As mentioned [earlier], these lipids are not that challenging to measure with modern clinical mass spectrometers, but a plasma or serum biomarker would be better for MS and it is probably only a matter of time until we find a good one. I am not a clinical practitioner and they may have a different perspective," Don said.

REFERENCES
1. Shi L, Ghezzi L, Fenoglio C, et al. CSF sphingolipids are correlated with neuroinflammatory cytokines and differentiate neuromyelitis optica spectrum disorder from multiple sclerosis. J Neurol Neurosurg Psychiatry. 2024;96(1):54-67. Published 2024 Dec 16. doi:10.1136/jnnp-2024-333774
2. Thompson AJ, Banwell BL, Barkhof F, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018;17(2):162-173. doi:10.1016/S1474-4422(17)30470-2
3. Wingerchuk DM, Banwell B, Bennett JL, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 2015;85(2):177-189. doi:10.1212/WNL.0000000000001729

A study identified specific cerebrospinal fluid (CSF) lipids that differentiate multiple sclerosis (MS) from neuromyelitis optica spectrum disorder (NMOSD) and other neurological diseases, suggesting potential biomarkers for diagnosis and monitoring. Researchers screened 353 lipid species, finding significant differences, particularly in NMOSD. A machine-learning approach identified three lipids achieving high sensitivity and specificity in differentiating NMOSD from MS. CSF lipids correlated with inflammatory cytokines and disease activity measures. Despite promising results, limitations include small sample size and lack of healthy controls, necessitating further research for validation.

Cerebrospinal fluid lipid profiling revealed potential biomarkers for distinguishing NMOSD from MS and tracking disease activity, offering new insights into neuroinflammatory disease monitoring. 

Cerebrospinal Fluid Lipids Shows Promise as Biomarkers for Differentiating NMOSD and MS

Nearly 4 and a half years since its original submission, the FDA has approved Supernus Pharmaceuticals’ investigational agent SPN-830 (Onapgo) as the first and only subcutaneous apomorphine infusion device for the treatment of motor fluctuations in adults with advanced Parkinson disease (PD). The company also noted that it will make SPN-830 available in the second quarter of 2025 with a support team of experts, including a robust nurse education program, and access support at launch.

"People living with Parkinson's and their families are hungry for new treatment options, and the PMD Alliance community was thrilled to learn about SPN-830's approval. Every newly approved Parkinson's therapy is a win for our community," 

 in a recent interview. "The introduction of this therapy brings with it an increased need for education, and underscores the importance of clinician-patient communication. PMD Alliance produces resources and education to help patients understand their symptoms, for personal empowerment, but also to streamline clinic visits. Our annual healthcare provider conference, 

Advanced Therapeutics in Movement and Related Disorders (ATMRD)

, equips clinicians with the information to integrate new therapies into practice."

The therapy’s approval was based on data from the TOLEDO study (NCT02006121), a randomized, double-blind study in which treatment with the device was associated with a difference of –1.89 hours per day of OFF time for patients with PD in comparison with placebo. Published in the 

in 2018, the study randomly assigned 106 patients living with the disease to either 3-mg/hour to 8-mg/hour dose of apomorphine (n = 53) or placebo saline infusion (n = 53) during their wake hours for a 12-week period.

"Hope is strong after this approval, the third in less than a year. Combined with momentum from the 

 being signed into law, 2025 has the potential to be a banner year for people living with Parkinson's and the healthcare providers caring for them," Merriam said. 

In TOLEDO, the intervention group, with a mean final drug dose of 4.68 mg/hour, showed significant improvements, including a reduction in OFF time of –2.47 hours/day compared with –0.58 hours/day for placebo (

 = .0025), and an increase in ON time without troublesome dyskinesia of 2.77 hours/day versus 0.80 hours/day for placebo (

 = .0008). Additionally, 62% of the apomorphine group were responders compared with 29% in the placebo group (P = .0008).

"The approval of ONAPGO (SPN-830) is a significant milestone in Parkinson’s disease management. As advanced practice providers, we play a critical role in optimizing treatment plans and ensuring patients have access to the best available therapies," 

Association of Movement Disorder Advanced Practice Providers (AMDAPP)

 in an interview. "The long-awaited approval of ONAPGO opens another valuable tool in our clinical toolbox, giving us a new option to address motor fluctuations and improve “on” time for our patients. This therapy has the potential to be a game-changer, helping us provide more individualized and effective care to those living with Parkinson’s. Additionally, as more therapies like this are approved, it reinforces the need for continued innovation in drug development, particularly in delivering more consistent symptom control without relying solely on oral medications."

The timeline for SPN-830 dates back to September 2020, when Supernus sent its original new drug application (NDA) to the FDA.

 Shortly after, the FDA issued a refusal to file letter indicating that the NDA was not sufficiently complete to permit a substantive review. Nearly a year later, in December 2021, the company resubmitted its NDA; however, it was once again met with resistance, as the FDA 

In the CRL, the agency noted that it required additional information and analyses related to the device, including labeling, product quality and manufacturing, device performance, and risk analysis. At the time, no additional efficacy or safety clinical studies were required. Notably, the FDA mentioned in the letter that the application's approval would require inspections that could not be completed in a timely manner, primarily because of travel restrictions amid the COVID-19 pandemic.

 for SPN-830 in October 2023 which was subsequently accepted by the FDA less than a month later.

 In April 2024, the FDA issued another CRL for the device, citing 2 areas that required additional review or more information.

 The first was related to product quality while the second related to the master file for the infusion device, which is proprietary to the device manufacturer. Supernus went back to make adjustments and thus, towards the latter half of 2024, the company announced that the FDA accepted its resubmission of the NDA for SPN-830, giving it a PDUFA date of February 1, 2025.

"The approval of SPN-830 is incredibly exciting! Extensive data supports its effectiveness, as it has been used in other regions for decades—dating back 29 years in Europe. As more treatment options become available for people living with Parkinson’s disease, we, as clinicians, can better tailor treatment plans to each individual’s unique needs and best interests," Erin Zinn, MSN, APRN-CNP, ANP-BC, CMRD, director of Operations & Strategy at AMDAPP, told 

. "SPN-830 represents yet another groundbreaking option for managing PD. This is an exciting time in the movement disorders community, with new advancements offering hope for improved quality of life for those with Parkinson’s."

Updates in Therapeutic Development: Clinical Trial Readouts to Watch in the First Half of 2025

At the end of the treatment period in TOLEO, patients on SPN-830 experienced a mean reduction in OFF time of –2.47 hours per day (SD, 3.70) compared with –0.58 hours per day (SD, 2.80) for those on placebo (

 = .0025). Investigators suggested that this therapy could potentially reduce the need for higher doses of concomitant oral antiparkinsonian medications.

Additional data from the study showed that 62% of patients on SPN-830 achieved at least a 2-hour reduction in OFF time compared with 29% of those on placebo. Overall, 71% of the SPN-830 group reported improvements in their general health compared with 18% in the placebo group. Patients on the active treatment also experienced a 2.77-hour/day increase in ON time without troublesome dyskinesia and significantly improved Patient Global Impression of Change scores (

 < .001). While reductions in oral levodopa dose were not significant (

 = .0615), SPN-830 led to a significantly greater reduction in levodopa-equivalent dose than placebo (

"This therapy is particularly beneficial for patients with moderate to advanced Parkinson’s disease who struggle with unpredictable OFF periods despite optimized oral treatment, as demonstrated in the TOLEDO study. By bypassing the gastrointestinal system, ONAPGO ensures more reliable medication absorption, which is critical for those with delayed gastric emptying or erratic response to oral levodopa," Zinn explained. "As with any infusion therapy, proper patient selection, dose titration, and monitoring are essential to maximize benefits while minimizing side effects such as nausea, hypotension, and skin reactions at the infusion site. All of which we can prepare for and manage well with proper education."

Apomorphine was first approved in 2004 under the brand name Apokyn for the acute, intermittent treatment of OFF episodes in PD. Apokyn is different from SPN-830, as it is administered by subcutaneous injection with a multiple-dose pen injector that can be used up to 5 times a day, with doses no less than 2 hours apart. Apomorphine works as a dopamine agonist that binds with high affinity to the dopamine D4 receptor, and moderate affinity for the dopamine D2, D3, and D5, and adrenergic α1D, α2B, α2C receptors.

"As APPs, we play a pivotal role in educating patients, initiating therapy, titrating doses, and troubleshooting infusion management to ensure the best possible outcomes. Hands-on training and education will be key to equipping providers with the skills needed to implement this therapy effectively," Papesh said. "At AMDAPP, we are committed to supporting APPs with the education and resources needed to integrate ONAPGO into clinical practice. We will do all we can to bring hands-on training and education to the community to ensure providers feel confident using this new treatment option."

In TOLEDO, SPN-830 was generally well tolerated, with no unexpected safety concerns. Most adverse events (AEs) were mild or moderate, and no deaths occurred. TEAEs were reported in 93% of patients on SPN-830 compared with 57% on placebo, with common AEs including skin reactions, nausea, and somnolence. A higher proportion of patients in the apomorphine group experienced AEs requiring dose modification.

“The approval of a new device that delivers a drug for folks with Parkinson’s disease, using an under the skin technology, and not requiring a wire in the brain or a tube in the stomach, is a huge advantage for many folks looking to improve their Parkinson’s disease symptoms," 

 and director of the Norman Fixel Institute for Neurological Diseases, told 

 in a recent interview. “This therapy has been under development for many years and finally got over the hurdle for FDA approval. We know from studies that have been published in journals like the 

 that the number of hours of ‘good quality on medication time’ for folks with Parkinson will potentially increase about two hours. This is a meaningful change.”

Six patients in the SPN-830 group withdrew from the study due to AEs. Three of these withdrawals were due to serious events: severe hypotension, myocardial infarction, and abnormal hematology results indicating mild leucopenia and moderate anemia (non-hemolytic). The remaining three withdrawals were attributed to visual hallucinations, moderate gait disturbance, and mild infusion-site erythema. Except for myocardial infarction, all AEs leading to withdrawal were considered treatment-related and resolved after discontinuation of SPN-830.

“The pump seems to be very well tolerated, however it will likely translate in the real world to requiring some maintenance, and we therefore believe that having really great care partners, which is something important in Parkinson’s disease outcomes, will be critical for folks interested in this pump technology," Okun said in the interview with 

. “This is the second subcutaneous pump recently approved by the FDA for treatment Parkinson’s disease and is great news for many of the folks who are suffering what we refer to as motor fluctuations; where their symptoms are bouncing up and down from feeling completely off medication to experiencing, in some cases dance like movements called dyskinesia.”

 “Though we are excited to see another pump therapy, and especially one that is under the skin and less invasive than other technologies, we will crucially need to learn how to apply this pump in clinical practice. We will need to understand what persons with [Parkinson] disease will benefit the most from this therapy, and also when to pull the trigger for more aggressive therapy like deep brain stimulation or focus ultrasound," Okun explained. 

REFERENCES
1. Supernus Announces FDA Approval of ONAPGO™ (apomorphine hydrochloride) for Parkinson’s Disease. News Release. Supernus. Published February 4, 2025. Accessed February 4, 2025. https://ir.supernus.com/news-releases/news-release-details/supernus-announces-fda-approval-onapgotm-apomorphine
2. Katzenschlager R, Poewe W, Rascol O, et al. Apomorphine subcutaneous infusion in patients with Parkinson's disease with persistent motor fluctuations (TOLEDO): a multicentre, double-blind, randomized, placebo-controlled trial. Lancet Neurol. 2018;17(9):749-759. doi:10.1016/S1474-4422(18)30239-4
3. Supernus Submits NDA for SPN-830 for Continuous Treatment of ON-OFF Episodes in Adults with Parkinson’s Disease Who Have Failed Two Treatments. News release. Supernus Pharmaceuticals. September 14, 2020. Accessed February 1, 2025. https://ir.supernus.com/news-releases/news-release-details/supernus-submits-nda-spn-830-continuous-treatment-episodes
4. Supernus Resubmits NDA for SPN-830 Apomorphine Infusion Device. News release. December 8, 2021. Accessed February 1, 2025. https://ir.supernus.com/news-releases/news-release-details/supernus-resubmits-nda-spn-830-apomorphine-infusion-device
5. Supernus Provides Regulatory Update on SPN-830. News release. Supernus Pharmaceuticals. October 2022. Accessed February 1, 2025. https://ir.supernus.com/news-releases/news-release-details/supernus-provides-regulatory-update-spn-830
6. Supernus resubmits NDA for SPN-830 apomorphine infusion device. News release. Supernus Pharmaceuticals. October 9, 2023. Accessed February 1, 2025. https://ir.supernus.com/news-releases/news-release-details/supernus-resubmits-nda-spn-830-apomorphine-infusion-device-0
7. Supernus Provides Regulatory Update for SPN-830. News Release. Supernus Pharmaceuticals. Published April 8, 2024. Accessed February 1, 2025. https://ir.supernus.com/news-releases/news-release-details/supernus-provides-regulatory-update-spn-830-0
8. Supernus Announces SPN-830 Apomorphine Infusion Device NDA Accepted for Review by FDA. News release. Supernus Pharmaceuticals. August 19, 2024. Accessed February 1, 2025. https://ir.supernus.com/news-releases/news-release-details/supernus-announces-spn-830-apomorphine-infusion-device-nda-0

Supernus Pharmaceuticals' SPN-830 (Onapgo) has been approved by the FDA as the first subcutaneous apomorphine infusion device for advanced Parkinson's disease, reducing motor fluctuations. The approval was based on the TOLEDO study, which demonstrated significant reductions in OFF time and increases in ON time without dyskinesia. Despite initial regulatory challenges, the device will be available in 2025. SPN-830 offers a non-invasive alternative to manage motor symptoms, bypassing gastrointestinal issues associated with oral medications, and providing more predictable symptom control.

SPN-830 is a wearable subcutaneous infusion device designed to deliver continuous treatment throughout the waking day, ensuring more consistent control of OFF time.

FDA Approves Apomorphine Infusion Device SPN-830 as New Parkinson Treatment

’ resubmission of its new drug application (NDA) in September 2024, the agency has approved AXS-07, an oral, rapidly absorbed, multi-mechanistic agent, as a new acute treatment of migraine with or without aura in adults. Marketed as Symbravo, the company noted that it anticipates AXS-07 to be commercially available in the United States in approximately 4 months.

AXS-07, a novel agent, is thought to act by inhibiting calcitonin gene-related peptide (CGRP) release, reversing CGRP-mediated vasodilation, and inhibiting neuroinflammation, pain signal transmission, and central sensitization. The agent, which consists of meloxicam and rizatriptan, is enabled by Axsome’s MoSEIC (Molecular Solubility Enhanced Inclusion Complex) technology, which results in faster absorption and longer plasma half-life.

"In terms of use in clinical practice, we want to treat our patients with the simplest, most effective acute treatments that we're able to offer them. So, you would not use a combination triptan and non-steroidal product in a patient whose treatment needs were fully met, either by a triptan alone or by a non-steroidal anti-inflammatory alone," 

, professor of neurology and director of the Montefiore Headache Center at 

 in a recent interview. "In fact, the design for individuals with unmet needs on single, monotherapy acute treatments was specifically a reflection of the fact that those are the patients who need combination therapy. I think that's something most prescribers would do and should do."

 for its NDA submission of AXS-07, citing issues related to the chemistry, manufacturing, and controls considerations. At the time, the agency did not request any new clinical trials to be conducted.

The FDA has approved AXS-07 (Symbravo), a novel oral treatment for acute migraine in adults, developed by Axsome Therapeutics. AXS-07 combines meloxicam and rizatriptan, utilizing MoSEIC technology for rapid absorption and extended plasma half-life. Clinical trials, including MOMENTUM and INTERCEPT, demonstrated significant efficacy in achieving pain freedom and reducing migraine symptoms compared to placebo. The approval addresses unmet needs in migraine treatment, offering a new option for patients with inadequate response to existing therapies. AXS-07 is expected to be available in the U.S. within four months.

Findings from previous phase 3 trial showed that treatment with AXS-07 resulted in significant reductions in headache pain freedom, migraine symptoms, and rescue medication use.

Tamara Kaplan, MD

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