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Parkinson Cell Therapy ANPD001 Generates Promising Early-Stage Phase 1/2 Data
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Key Takeaways
- ANPD001, an iPSC-derived therapy, showed safety and early efficacy in a phase 1/2 trial for Parkinson's disease over six months.
- The ASPIRO trial demonstrated significant improvements in motor function and daily living activities, with no severe complications reported.
Early findings from the ASPIRO trial showed ANPD001 was safe, well-tolerated, and led to marked improvements in motor symptoms and daily functioning.
Avram Fraint, MD, MS
New findings from 3 individuals in a first-in-human, phase 1/2 trial (NCT0634406) showed that treatment with ANPD001 (Aspen Neuroscience), an investigational autologous induced pluripotent stem cell (iPSC)-derived therapy, was safe and resulted in early signs of efficacy, including improvements in OFF and good ON time, over a 6-month treatment period.1,2
Published in Parkinsonism and Related Disorders, extended details from the study, also known as ASPIRO, will be presented at the 30th World Congress on Parkinson’s Disease and Related Disorders, held May 7-10 in New York. ASPIRO, an open-label trial, comprised patients aged 50 to 70 years old with moderate to severe Parkinson disease (PD), primarily testing the safety and tolerability of 2 doses of ANPD001, an iPSC-derived dopaminergic neuronal precursor cells (DANPCs).
Over the 6-month observed period, investigators found no cases of hemorrhages, serious intra- or post-operative complications, as well as any severe graft-induced dyskinesia for those treated with ANPD001. At follow-up, the most common adverse event (AEs) was swollen tongue, recorded in 2 patients. Other AEs included back pain, hypoesthesia, incision site pain, musculoskeletal stiffness, tongue injury, and urinary retention, which were all related to the procedure. Post-lumbar puncture headache, observed in 1 individual, was considered not related.
"Parkinson's disease is the second most common neurodegenerative disorder. By the time of diagnosis, most people with Parkinson's have lost the majority of their dopaminergic neurons, leading to progressive loss of motor and non-motor function," Avram Fraint, MD, MS, neuroscience medical director at Aspen, said in a statement.1 "To date, data from the first three patients in the ASPIRO study show that precision delivery of personalized DANPCs is safe and well-tolerated."
While the most recent data focused on 6-month outcomes, the company expects to report on primary safety and efficacy end points at 12 months, with continued follow-up and evaluation lasting for 5 years. The study, which excludes patients with cognitive impairment and other comorbidities that make them high-risk for an intra-cranial therapy, will also test the therapy’s safety over a long-term period, lasting up to 15 years. Considered the first multi-patient, multicenter trial of an autologous cell therapy for PD, patients included are under the care of a movement disorder specialist throughout.
In addition to MRI confirming precision implantation of DANPCs into the intended target, 6-month data showed an average improvement of 45% (range, 33-55%) in Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part III OFF scores compared with baseline. In addition, treated patients demonstrated a 71% (range, 41-93%) improvement in MDS-UPDRS Part II score, which tests motor experiences of daily living. Furthermore, there was an average reduction of 2 hours in adjusted OFF time and a 1.5-hour average increase in adjusted good ON time.
Aspen’s personalized 3-step manufacturing process begins with a small sample of the patient’s skin cells, which are reprogrammed into induced pluripotent stem cells and then differentiated into DANPCs. These DANPCs are surgically delivered to the patient to replace cells lost or damaged by disease. At every stage, cell quality is evaluated using Aspen’s proprietary AI-driven genomics assay.
"In this first-of-its-kind study, we are seeing clinician-reported and patient-reported improvements as well as a strong safety and tolerability profile at six months. Importantly, ANPD001 has the unique advantage of not requiring immunosuppression," Edward Wirth III, MD, PhD, chief medical officer at Aspen, said in a statement.1
Prior to ASPIRO, ANPD001 was tested in a preclinical study to see if it had the ability to manufacture patient-specific DANPCs. Presented at the 2023 World Parkinson Congress, the DANPCs were created from 6 different skin biopsies, which were donated by patients with PD. Following that, multiple iPSC clones were produced and identified from the donors individually. The autologous iPSCs were then distinguished into DANPCs, which were then assessed for efficacy in a well-known animal model of PD.3
In the animal model, researchers observed no migration or tumor formation, suggesting that the PD neurons in vitro and restore dopamine signaling deficits. For context, Safety, biodistribution, and tumorigencity of the DANPCs were characterized in intact immunodeficient Rowett nude rats under Good Laboratory Practices (GLP). In the study, 4 lines were tested for efficacy in a 6-OHDA medial forebrain bundle lesion rodent model of PD, with histological examinations to determine survival, phenotype, and innervation of the resulting grafts.
