Levetiracetam

TUESDAY, Jan. 6, 2026 -- More than two-thirds of pregnant women with epilepsy (PWWE) receiving antiseizure medications (ASMs) have dose increases during pregnancy, according to a study published online Dec. 29 in Neurology . Page B. Pennell, M.D., from the University of Pittsburgh School of Medicine, and colleagues examined how ASMs were dosed in a large observational cohort study of PWWE, ages 14 to 45 years and at <20 weeks' gestational age, who had favorable seizure outcomes. The percentage of participants who underwent dose changes was examined in pregnancy and postpartum for each ASM. Overall, 299 participants were eligible for analysis. The researchers found that 67.8 percent of ASMs had dose increases during pregnancy, beginning at a median of 32 days post-enrolment. For 47.9 percent of ASMs, dose decreases were made within six weeks postdelivery, beginning at a median of three days postpartum. For lamotrigine, 87.7 percent of participants had doses increased, by a median of 100 mg/day, reaching a mean of 191 percent of conception dose by delivery; 70.5 percent had dose tapers by a median of 100 mg/day postpartum, reaching a mean of 116 percent of conception dose by six weeks. For levetiracetam, 56.0 percent had doses increased by a median of 500 mg/day, reaching 177 percent of the mean conception dose by delivery; 34.4 percent had dose tapers postpartum, to 136 percent of the conception dose by six weeks. "Our goal was to generate practical evidence that empowers clinicians everywhere -- from rural hospitals to urban subspecialty centers -- to provide the best possible care for women with epilepsy during pregnancy," Pennell said in a statement. Several authors disclosed ties to the biopharmaceutical industry. Abstract/Full Text (subscription or payment may be required) Editorial (subscription or payment may be required)

Post-hoc analysis of RAP-219 Phase 2a data showed early onset of action and consistency of median response over the entire treatment period, along with consistent efficacy data regardless of patients’ disease severity RAP-219 demonstrated meaningful improvements in patient-reported seizure severity among those with moderate or greater baseline impairment Dec. 05, 2025 -- Rapport Therapeutics, Inc. (Nasdaq: RAPP) (Rapport or the Company), a clinical-stage biotechnology company dedicated to the discovery and development of small molecule precision medicines for patients with neurological or psychiatric disorders, today announced new data and post hoc analysis on clinical and patient reported benefits of RAP-219 in drug-resistant focal onset seizures (FOS), alongside topline efficacy and safety data from its recently reported Phase 2a FOS trial. The results were presented at the 2025 American Epilepsy Society (AES) Annual Meeting and include RAP-219’s early treatment effects and consistent median efficacy data across the full treatment period, its performance across varying levels of baseline disease severity, and its impact on seizure severity. “These additional results build upon the robust efficacy data we observed in the Phase 2a trial and further expand the growing body of evidence supporting RAP-219’s potential as a best-in-class anti-seizure medication for patients with drug-resistant focal onset seizures,” said Jeffrey Sevigny, M.D., chief medical officer of Rapport. “Our analysis showed that RAP-219 demonstrated strong clinical response - early in treatment, consistent over time, and across the spectrum of disease severity. Additionally, RAP-219 substantially reduced the impact of seizures on patients’ daily functioning, reinforcing its potential to make a meaningful difference in the lives of patients with epilepsy. With these results, we believe we are well positioned to advance into registrational trials, as we continue the development of RAP-219 as a potential therapy for people living with epilepsy.” The Company plans to hold an end-of-Phase 2 meeting with the U.S. Food and Drug Administration this quarter and anticipates initiating two pivotal Phase 3 trials of RAP-219 using traditional clinical seizure endpoints in the third quarter of 2026. Rapport announced topline results from the Phase 2a study in September 2025. The trial enrolled 30 participants and met the primary endpoint, demonstrating a statistically significant reduction in long episodes (LEs) compared with baseline over the 8-week treatment period. Study participants achieved a 77.8% reduction in clinical seizures compared with baseline (p=0.01), with 24% achieving seizure freedom during the 8-week treatment period (p<0.0001). RAP-219 was generally well-tolerated in the trial, with the majority of treatment-emergent adverse events (TEAEs) being mild and a low (10%) discontinuation rate. RAP-219 demonstrated early treatment clinical response and consistent, clinically meaningful median reductions throughout the 8-week treatment period, as assessed by change in LE and clinical seizure frequency during treatment weeks 1-4, 5-8, and 1-8 (overall). RAP-219 provided a consistent and clinically meaningful response regardless of patients’ baseline disease severity, as assessed by ≥30% LE and ≥50% clinical seizure responder rates. In patients with a median baseline LE frequency of ≤48 and >48, 85.7% and 84.6% achieved ≥30% reduction in LE frequency, respectively In patients with a median baseline clinical seizure frequency of ≤10 and >10, 69.2% and 75% achieved ≥50% reduction in clinical seizure frequency, respectively Seizure freedom was achieved over the entire 8-week treatment period at a similar rate regardless of baseline clinical seizure frequency (23.1% in patients with ≤10 baseline clinical seizures; 25% in patients with >10 baseline clinical seizures) The primary goal of ASM treatment is to eliminate or markedly reduce seizures, but it’s also important to lessen the impact on daily activity of any seizures that persist. Treatment with RAP-219 improved overall seizure intensity as well as time to recovery, ability to concentrate, and reduced seizure interference with daily activity following a seizure, as measured by the Seizure Severity Response Questionnaire (SSRQ). Improvements in these domains suggest the potential of RAP-219 to improve quality of life in patients with drug-resistant FOS. In this post-hoc analysis, change in seizure severity in patients treated with RAP-219 was assessed in those patients reporting moderate or greater (>4 out of 10) impairment at baseline in the domains measured by the SSRQ. At week 8, patients experienced significant median percent decreases from baseline in 3 of the 4 domains assessed: time to recovery (n=8; 100%, P=0.195), ability to think or concentrate after a seizure (n=15; 71.4%, P=0.013), interference with daily activity (n=12; 94.4%, P=0.002), and overall intensity (n=15; 75%, P=0.001). Rapport also presented data that (1) confirmed the expression and distribution of TARPγ8 in the cortex and mesial temporal lobes, the brain regions where seizures originate and propagate, and (2) demonstrated that therapeutic concentrations of RAP-219 are achieved after 2 weeks of daily dosing across a range of doses. The proof-of-concept, multi-center, open-label Phase 2a clinical trial was designed to evaluate the efficacy, safety, and tolerability of RAP-219 in adult patients with drug-resistant focal onset seizures. The trial enrolled 30 patients with focal onset seizures who had an implanted RNS® System. Patients received 0.75 mg RAP-219 oral tablet daily for 5 days followed by 1.25 mg RAP-219 oral tablet daily for the remainder of the 8-week treatment period. The primary efficacy endpoint was the change in frequency of RNS-recorded long episodes (LEs) in patients with focal onset seizures evaluated both as the proportion of responders achieving ≥30% reduction in LEs from baseline, which has been demonstrated to be associated with ≥50% reduction in clinical seizures, and median percent change from baseline in LE frequency. Secondary endpoints included clinical seizure frequency reductions (assessed as median percent change from baseline, responder proportion who achieve a ≥50% reduction in seizure frequency, and seizure freedom), safety, and tolerability. The trial enrolled 12 women and 18 men, and the mean age of patients enrolled was 40.1 years. The mean age of enrolled patients at the time of their first seizure was 16.6 years. Patients were taking a median of 3 concomitant antiseizure medications, with the highest proportion of patients taking lamotrigine (50%), levetiracetam (40%), and cenobamate (37%) medications. These demographics and baseline characteristics are consistent with that of patients expected to be enrolled in future registrational trials of RAP-219. RAP-219 is a potential first-in-class, clinical-stage TARPγ8-specific AMPA receptor (AMPAR) negative allosteric modulator (NAM). Whereas AMPARs are distributed widely in the central nervous system, the receptor associated protein (RAP) TARPγ8 is expressed only in discrete brain regions, including the hippocampus and neocortex, where focal seizures often originate. By contrast, TARPγ8 has minimal expression in the hindbrain, where drug effects are often associated with intolerable adverse events. With this precision approach, the Company believes RAP-219 has the potential to provide a differentiated profile as compared to traditional neuroscience medications. Due to the role of AMPA biology in various neurological disorders and the selective targeting of TARPγ8, the Company believes RAP-219 has pipeline-in-a-product potential and is evaluating the compound as a potential treatment for patients with focal onset seizures, bipolar disorder, and peripheral neuropathic pain. Rapport is conducting an open-label long term safety trial to allow patients enrolled in the RAP-219-FOS-201 trial to continue RAP-219. Preliminary results of the trial are expected in the second half of 2026. Additionally, Rapport continues development of a long-acting injectable (LAI) formulation of RAP-219. Up to half of patients are nonadherent to prescribed ASMs, which can present a significant issue in optimizing treatment benefit and lead to potential breakthrough seizures. The Company believes a LAI formulation has the potential to improve patient adherence and expand the potential clinical utility across all of RAP-219’s indications. Outside of epilepsy, Rapport is evaluating RAP-219 in a Phase 2 trial in bipolar mania. The trial is currently enrolling patients and is on track, with topline results expected in the first half of 2027. An update on next steps for a Phase 2 trial in diabetic peripheral neuropathic pain is expected in the first quarter of 2026. Rapport Therapeutics is a clinical-stage biotechnology company dedicated to discovering and developing small molecule precision medicines for patients with neurological or psychiatric disorders. The Company’s founders have made pioneering discoveries related to the function of receptor associated proteins (RAPs) in the brain. Their findings form the basis of Rapport’s RAP technology platform, which enables a differentiated approach to generate precision small molecule product candidates with the potential to overcome many limitations of conventional neurology drug discovery. Rapport’s precision neuroscience pipeline includes the Company’s lead investigational drug, RAP-219, designed to achieve neuroanatomical specificity through its selective targeting of a RAP expressed in only discrete regions of the brain. The Company is currently pursuing RAP-219 as a potential treatment for drug-resistant focal onset seizures, bipolar mania and diabetic peripheral neuropathic pain. Additional preclinical and late-stage discovery stage programs are also underway, including targeting chronic pain and hearing disorders. Rapport Therapeutics uses and intends to continue to use its Investor Relations website and LinkedIn (Rapport Therapeutics) as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD. Accordingly, investors should monitor the Company’s Investor Relations website and LinkedIn, in addition to following the Company’s press releases, SEC filings, public conference calls, presentations, and webcasts. The contents of the Company’s website or social media shall not be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended. The content above comes from the network. if any infringement, please contact us to modify.