New trials in neurology: What to watch in 2024
Key Takeaways
Three new and notable neurology trials include those aimed at improving diagnosis and treatment of excessive daytime sleepiness (EDS), Friedreich’s ataxia (FA), and Huntington’s disease (HD).
New gene therapies, especially, are showing promise in treating neurological conditions.
Current trials include the use of pitolisant in the treatment of EDS, LX2006 for cardiomyopathy in FA patients, and AMT-130 for early manifest HD.
The field of neurology is advancing at a rapid clip, with no sign of slowing any time soon. Experts believe that breakthroughs in basic, translational, and clinical neuroscience are driving enhancements in human health, the economy, and society overall.
Authors publishing in Journal of Neuroscience note that neurology is “at the nexus of many societal topics beyond medicine, including education, consumerism, and the justice system.”[]
On that note, here are three neurology trials to watch in 2024.
Excessive daytime sleepiness
In this phase 2 trial (Safety and Efficacy of Pitolisant on Excessive Daytime Sleepiness [EDS] and Other Non-Muscular Symptoms in Patients With Myotonic Dystrophy Type 1), researchers sought to assess the safety and efficacy of pitolisant vs placebo in the treatment of EDS in 30 patients with myotonic dystrophy type 1 aged 18 to 65 years.[]
As a secondary endpoint, researchers assessed the effects of pitolisant on fatigue, cognitive dysfunction, and burden of disease, as well as long-term safety and efficacy.
The study consisted of a 3-week titration period; an 8-week stable dose period; and an optional open-label extension phase. Patients were randomly titrated 1:1:1 to lower dose (17.8 mg); higher dose (35.6 mg); or placebo.
According to topline results of the trial published in December 2023, there was a clinically meaningful change in the first endpoint, or EDS as measured by the Daytime Sleepiness Scale (DSS).[] There was also a clinically meaningful change in the secondary efficacy endpoint measured by the Fatigue Severity Scale (FSS). Both EDS and fatigue occur in up to 90% of patients with myotonic dystrophy type 1 and compromise daily functioning to the same extent as muscular symptoms, including myotonia and muscle weakness.
"These strong topline results add to the body of evidence supporting the effectiveness of pitolisant for improving EDS," stated Jeffrey M. Dayno, MD, CEO of Harmony Biosciences in the press release. "In addition, a positive signal for pitolisant has been demonstrated for fatigue, suggesting it could be a potential new treatment option for this symptom as well."
The mechanism of pitolisant remains to elucidated but could function as an antagonist/inverse agonist against H3 receptors.[]
Friedreich's ataxia (FA) with evidence of cardiomyopathy
SUNRISE-FA is a multicenter, 52-week, dose-ascending, open-label trial assessing the safety and tolerability, along with preliminary efficacy, of LX2006 in patients diagnosed with Friedreich's ataxia (FA) with evidence of cardiomyopathy.[]
This trial (Phase 1/2 Study of the Safety and Efficacy of LX2006 Gene Therapy in Participants With Cardiomyopathy Associated With Friedreich's Ataxia) evaluates three doses of a single administration of LX2006, an adeno-associated virus (AAV) gene therapy developed to deliver the human frataxin (hFXN) gene to cardiac cells during a 52-week period. The study will take 5 years, with an additional 4 years dedicated to the assessment of long-term safety and efficacy of the intravenous treatment.
Currently no treatment exists to change the progression of cardiomyopathy in FA. Such cardiomyopathy leads to 59% of deaths secondary to FA.
In preclinical studies, LX2006 reversed cardiac abnormalities in FA disease models and demonstrated improvement of heart function and survival, while remaining safe.[] The FDA has granted Rare Pediatric Disease designation and Orphan Drug designation to LX2006 for the treatment of FA.
LX2006 was well tolerated with no new safety signals in the first-dose cohort. Consequently, investigators are now dosing a second cohort.
In the press release, R. Nolan Townsend, CEO of LEXEO Therapeutics, remarked, “The advancement of SUNRISE-FA helps pave the way for a potential life-altering treatment for patients with FA cardiomyopathy. Because no approved therapy has been shown to treat the cardiac manifestations of FA, a significant unmet need persists for these patients. We look forward to continuing to progress this program with data readouts expected in the first half of 2024.”
Huntington's disease
In a phase 1/2 randomized, multicenter, multiple dose, double-blind, imitation surgery, first-in-human trial, researchers assessed AMT-130 in patients with early manifest Huntington’s disease (Safety and Proof-of-Concept [POC] Study With AMT-130 in Adults With Early Manifest Huntington's Disease [HD]).[]
AMT-130 is an investigational, single administration gene therapy that is meant to modify the disease trajectory in patients with HD. In preclinical studies, AMT-130 decreases the levels of huntingtin protein and is related to the decreased progression of HD signs in animal models.
Cohort 1 and 2 involve a blinded 12-month core study period to assess the safety and potential impact of AMT-130 on disease progression, along with an unblinded 4-year long-term period with follow-up visits to evaluate the safety of AMT-130 and disease progression.
Cohort 2 sham participants who do not cross over to receive AMT-130 treatment can later partake of the optional extended follow-up period, with 2 more years of follow-up.
Cohort 3 patients will be administered AMT-130 either at the high or the low dose. At 12 months, these participants will be unblinded to their treatment arm. Cohort 3 will additionally assess the safety and exploratory efficacy data of low- or high-dose AMT-130, along with peri- and post-operative glucocorticoids.
“The clinical assessment trends in the ongoing studies of AMT-130 look very promising and continue to show disease stability in Huntington’s disease patients treated with this one-time administered gene therapy, several of whom have now been followed more than two years,” said Walid Abi-Saab, MD, chief medical officer of uniQure, in a press release.[] “We are observing favorable trends in evaluation of motor skills, functional independence, and composite rating scores as compared to a non-concurrent criteria-matched natural history cohort.”
He continued: “We also are pleased to observe further declines in levels of NfL, a measurement of neuronal degradation and disease progression, with low-dose patients below baseline at 30 months of follow-up and high-dose patients near baseline at 18 months."
Dr. Abi-Saab also notes that AMT-130 continues to be well-tolerated and safe at both low and high doses, and that oversight of trial participants will continue. "[We] look forward to initiating regulatory interactions next year,” he concluded.
What this mean for you
Clinical trials making headway in 2024 will contribute to treatment developments of several conditions, including HD, FA, and EDS. In particular, gene therapies are a hot topic in neurology research. Advances in neurology treatments warrant interest from both neurologists and primary care physicians.