In the field of neurology, drug development has experienced significant growth over the years, driven by unprecedented funding and the introduction of the first disease-modifying therapies. Hundreds of ongoing clinical trials and various stages of development are actively evaluating potential drugs for patients to address neurological conditions. With this prolific activity, keeping abreast of the latest discoveries can be a challenge. NeurologyLive® will therefore closely monitor the expected data readout from his five clinical trials scheduled for 2024.
Myotonic Dystrophy Type 1: Pitolisant Phase 2 Signal Detection Study (NCT04886518) (Harmony Biosciences)
Myotonic dystrophy type 1 (DM1) is associated with the most prominent sleep disturbances, including excessive daytime sleepiness (EDS), sleep apnea, periodic leg movements during sleep, and REM sleep dysregulation. It is a chronic neuromuscular disease. Sleep disturbances associated with DM1 may resemble those observed in narcolepsy, which is associated with decreased orexin levels in the cerebrospinal fluid.
Harmony Biosciences will share the complete dataset of its pivotal Phase 2 signal biomarker detection study (NCT04886518) evaluating pitolisant (Wakix) in myotonic dystrophy type 1 patients with EDS in early 2024 It is expected to be. The study will involve 30 DM1 patients aged 18 to 65 years who will be followed through a 3-week titration phase, an 8-week stable dose period, and an optional open-label extension period. In this trial, patients are randomly assigned in a 1:1:1 ratio to either high or low doses of Pitolisan or a placebo.1
In December 2023, the company announced topline data from the study, which showed pitolisant improved both EDS and fatigue over an 11-week treatment period. Overall, patients receiving high and low doses of pitolisant had mean changes in the primary efficacy endpoint, the Daytime Sleepiness Scale (DSS), of -2.5 and -1.0 compared with those receiving placebo. A change of -0.2 was reported in patients with For the Epworth Sleepiness Scale (ESS), researchers reported a mean change of -4.88 for the high-dose pitolisant group and -0.10 for the placebo.
Dravet Syndrome: SWALLOWTAIL Extension Study of STK-001 (Stoke Therapeutics) (NCT04740476)
In June 2023, Stoke Therapeutics announced two ongoing Phase 1/2a trials evaluating the investigational antisense oligonucleotide STK-001 in children and adults with Dravet syndrome (DS). announced new positive findings. STK-001 utilizes the non-mutated (wild-type) copy of the gene to upregulate NaV1.1 protein expression and restore physiological NaV1.1 levels, thereby reducing seizure occurrence and severe It is designed to reduce both seizure comorbidities.
The Phase 1/2a trials, called MONACH (NCT04740476) and ADMIRAL (NCT04442295), are expected to be completed by the end of 2023, and the open-label extension, SWALLOWTAIL, is expected to have data readout in the first quarter of 2024.2 SWALLOWTAIL will include only patients who received a cumulative total dose of 30 mg or more of STK-001 in MONARCH and continued treatment at doses of 30 mg or 45 mg every 4 months.
Combining available data from 45 patients treated with multiple doses (30 mg, 45 mg, and 70 mg) of either MONARCH or ADMIRAL, the greatest reduction in seizure frequency was found in 2 Patients (n = 11) treated with ADMIRAL or ADMIRAL. In the ADMIRAL study, 70 mg was administered three times. Overall, researchers found that in the multiple ascending dose (MAD) 70 mg cohort of ADMIRAL, a median of 80% (n = 6) and 89% (n = 3) at 3 and 6 months post-dose, respectively. We observed a decrease in value.
Preliminary data from SWALLOWTAIL, which included 26 people with DS, showed that after 12 months, seizure frequency decreased and expressive and receptive communication improved significantly, as measured by the Vineland Adaptive Behavior Scale III. Shown. Patients treated with STK-001 also had improved scores on global impression of change, as reported by caregivers and clinicians.
Friedreich Ataxic Cardiomyopathy: SUNRISE-FA Study of Gene Therapy LX2006 (NCT05445323)
SUNRISE-FA is an ongoing, dose-escalation, open-label trial in which approximately nine patients with Friedreich’s ataxia (FA)-related cardiomyopathy are being followed for 52 weeks. The study, with data readout expected in early 2024, will evaluate the efficacy and safety of LEXEO’s gene therapy LX2006.
FA is a rare autosomal recessive disease caused by mutations in the autosomal frataxin (FXN) gene. Currently, there are no approved treatments that alter the progression of cardiomyopathy in FA, which is responsible for 59% of FA-related deaths. LX2006, administered as a one-time infusion, appears to target the cardiac symptoms of FA by delivering a functional FXN gene that promotes frataxin protein expression and restores mitochondrial function in cardiomyocytes. Designed.
The study’s three cohorts tested low-, mild-, and high-dose LX2006 with primary endpoints of safety demonstrated through treatment-emergent adverse events (TEAEs) and treatment-emergent serious events. Evaluate. Patients participating in this study will be between 18 and 40 years of age, have a confirmed genetic diagnosis of FA, and meet the protocol-defined range of antibodies and FA cardiomyopathy controls. Patients with uncontrolled diabetes, abnormal liver function, or active infection for which cardiac MRI was contraindicated were excluded from the study.
The cardiac involvement seen in FA is the result of mitochondrial proliferation, loss of contractile proteins, and subsequent development of myocardial fibrosis. The left ventricular wall thickens, with various phenotypic manifestations including concentric or asymmetric hypertrophy and dilated cardiomyopathy. Dilated cardiomyopathy and arrhythmia are associated with mortality in FA patients, whereas hypertrophic cardiomyopathy is not.Four
Trigeminal Neuralgia: NOE-101 Phase 2b LibraTN Study (Noema Pharma)
Trigeminal neuralgia is a chronic pain condition that affects the trigeminal nerve, which transmits sensation from the face to the brain, and is thought to affect 4 to 5 out of 100,000 people in the United States each year. This condition associated with nerve damage or lesions is a type of neuropathic pain. NOE-101, developed by Noema Pharma, is a highly selective, potent, and cell-permeable negative allosteric modulator of mGlu5 receptors that has been shown to be effective in controlling pain in animal models of neuropathic pain. Shown.
The Phase 2b trial evaluating NOE-101 (called LibraTN) is expected to read out data in the first half of 2024.Five Dosing in this 24-week, prospective, double-blind, randomized withdrawal, placebo-controlled study began in February 2022, weeks before the FDA approved Noema’s investigational new drug application (IND).
“NOE-101’s antinociceptive effects are explained by its unique chemical and physical properties and its ability to block nuclear membrane mGlu5 receptors, a receptor overexpressed in chronic pain,” Garibaldi said. said in a statement after the IND approval. “Its efficacy is similar to the gold standard achieved by morphine and the non-opiate duloxetine, but with significant potential advantages in terms of side effects and tolerance. The LibraTN study shows that NOE-101’s efficacy It will help you understand further.”Patients with TN-related pain. ”
Huntington’s disease: Phase 1/2 study of AMT-130 (uniQure)
In December 2023, uniQure announced: New 30 month interim data Results from an ongoing Phase 1/2 trial evaluating AMT-130, an investigational gene therapy for Huntington’s disease (HD). The results showed that treatment with the lower dose resulted in a 0.39 point difference in the Unified Huntington’s Disease Rating Scale (cUHDRS) at 30 months, and treatment with the higher dose resulted in a 1.24 point difference at 18 months, so the potential showed evidence of dose-dependent clinical benefit. .6
uniQure said it plans to begin dialogue with regulatory authorities in the first quarter of 2024 to discuss data from both trials and potential strategies for continued AMT-130 development. . New data from his ongoing Phase 1/2 trial of AMT-130, including additional follow-up data from treated patients, is then expected to be published in mid-2024. In the latest data readout, results were from the September 30, 2023 cutoff date and did not include efficacy and biomarker data from control patients who changed treatment.
Additional results from the readout showed that the therapy resulted in a 0.95 point difference in total functional capacity (TFC) at 30 months in the low-dose group and a 0.49 point difference in the high-dose group at 18 months. It was shown that there was a difference (baseline value, low dose group). dose, 11.9; high dose, 12.2). Additionally, patients receiving active treatment showed a 2.80-point difference in total motor score (TMS) at 30 months in the low-dose group and a 1.70-point difference at 18 months in the high-dose group (baseline values, the difference was 13.3 points for low dose; high dose, 12.1).
“These Phase 1/2 study results, along with further reductions in NfL, demonstrate a positive trend and potentially dose-dependent signal across multiple key clinical and functional measures. FRCP’s Dr. Edward Wilde continues to be very encouraged. Professor of Neurology at University College London’s Queen Square Institute of Neurology, consultant neurologist at the National Hospital for Neurology and Neurosurgery, and deputy director of the UCL Huntington Disease Center, said in a statement.
