The year 2024 saw significant progress in the development and approval of novel therapies for neuromuscular and movement disorders, marking advancements in treatment options and disease management strategies. Several key developments have shaped the landscape, offering hope for improved patient outcomes.
Parkinson's Disease: New Treatments and Biomarkers
AbbVie's foscarbidopa/foslevodopa (Vyallev) received FDA approval as the first and only subcutaneous 24-hour infusion of levodopa-based therapy for advanced Parkinson's disease, addressing motor fluctuations. This approval provides a new avenue for managing symptoms in patients with advanced disease. According to AbbVie, Medicare patients can expect coverage in the second half of 2025.
In addition, topline results from AbbVie’s phase 3 TEMPO-2 trial showed that tavapadon met its primary and secondary endpoints among patients with early Parkinson disease (PD). The company plans to submit a new drug application to the FDA in 2025.
Amneal Pharmaceuticals' IPX203, an oral extended-release carbidopa/levodopa formulation (Crexont), was also approved for Parkinson's disease, offering another option for managing symptoms through a combination of immediate-release and extended-release mechanisms.
Data from a phase 3 study showed that treatment with investigational buntanetap was safe and well tolerated, with noted improvements in motor and nonmotor activities, as well as cognitive function.
The FDA issued a letter of support for using the α-synuclein seed amplification assay (αSyn-SAA) biomarker in clinical trials for Parkinson's disease and related disorders. This decision, facilitated by collaboration between The Michael J. Fox Foundation and the Critical Path Institute, aims to accelerate therapeutic development by improving diagnostic precision.
Gene Therapy Advancements and Challenges
Intellia Therapeutics' CRISPR editing therapy NTLA-2001 demonstrated the ability to be safely redosed, according to data from a phase 1 trial in patients with transthyretin (ATTR) amyloidosis. "Today’s data showcase an exciting new platform advancement for Intellia and the field of gene editing," said John Leonard, MD, of Intellia. "For the first time ever, we demonstrated that redosing with CRISPR, utilizing our proprietary, nonviral LNP-based delivery platform, enabled an additive pharmacodynamic effect on the target protein."
Solid Biosciences presented long-term follow-up data from the phase 1/2 IGNITE-DMD study of SGT-001, a microdystrophin gene therapy for Duchenne muscular dystrophy (DMD), showing preservation of cardiac function in treated patients as they aged. Stephanie Salabarria, BHSc, and colleagues noted, "This is the first study that describes longitudinal cMRI findings in DMD subjects that have received microdystrophin gene therapy... Further studies are needed to better understand the effects of the DMD gene therapy in the heart and carefully quantify the extent of cardiac gene transfer."
However, the field also faced setbacks. Pfizer paused dosing in the crossover portion of the phase 3 CIFFREO trial of fordadistrogene movaparvovec for DMD after a patient death in the phase 2 DAYLIGHT study. The development of fordadistrogene movaparvovec has since been discontinued.
Neurogene’s NGN-401, a gene therapy for Rett syndrome, led to a life-threatening immune response in a patient, highlighting the risks associated with AAV vector-based gene therapies. The patient developed a systemic hyperinflammatory syndrome and was in critical condition.
Other Notable Developments
Sardocor’s SRD-001, a gene therapy for heart failure with preserved ejection fraction (HFpEF), received FDA fast track designation, and the first patients were dosed in the phase 1/2a MUSIC-HFpEF clinical trial. Roger Hajjar, MD, stated, "The enrollment of the first patients in this gene therapy trial will serve to validate the large body of work that has implicated deficiency of calcium cycling in HFpEF."
Alterity Therapeutics reported positive interim phase 2 data for ATH434 in multiple system atrophy (MSA), showing improvements in disability and biomarker assessments after 6 months. Final 12-month data from the trial are expected in the first half of 2025.
PTC Therapeutics' eladocagene exuparvovec (Kebilidi/Upstaza), a gene therapy for aromatic L-amino acid decarboxylase (AADC) deficiency, was approved by the FDA, marking the first gene therapy for direct administration to the brain approved in the United States.
These developments collectively underscore the rapid evolution of treatment strategies for neurological and cardiac disorders, with gene therapies and novel pharmacological agents leading the way toward improved patient care and disease management.
