Novo Nordisk Publishes Results from Embryonic Stem Cell-Derived Dopaminergic Cells for Parkinson’s Phase 1/2

Key Points

• A phase 1/2 trial of STEM-PD reported 12-month safety data in eight people with moderate Parkinson’s disease after bilateral putaminal transplantation of stem cell-derived dopaminergic progenitors.
• No serious adverse events were linked to the cell product, no tumor formation was seen on MRI, and no graft-induced dyskinesias were observed during the 12-month follow-up.
• One participant died from a pulmonary fungal infection during immunosuppression, and interim imaging showed signs consistent with graft survival in several participants.

STEM-PD, Novo Nordisk’s embryonic stem cell-derived therapy, reported 12-month primary safety results and interim efficacy findings from a phase 1/2 open-label, multicenter trial in Parkinson’s disease in Nature. The study evaluated a cryopreserved, off-the-shelf dopaminergic progenitor product derived from human pluripotent stem cells and delivered by bilateral intraputaminal transplantation.

Eight participants with moderate Parkinson’s disease were enrolled across two dose cohorts, with four patients in the low-dose group and four in the high-dose group. Seven participants completed 12-month follow-up. One participant in the high-dose cohort died 10 weeks after transplantation from a fungal pulmonary infection while receiving immunosuppression.

The study’s primary endpoint focused on adverse events and serious adverse events during the first 12 months after transplantation, along with MRI monitoring for space-occupying lesions. Ongoing follow-up will continue through 36 months to assess durability, clinical outcomes, and graft function.

Sidenote: STEM-PD was recently acquired by a company named Cellular Intelligence. We just interviewed them on the next steps for the therapy, and the AI platform they’ve developed. It looks pretty mean…. stay tuned.

Safety Findings

The trial reported three serious adverse events in three participants during the 12-month follow-up period:

• One low-dose participant required prolonged hospitalization after temporary worsening of parkinsonian symptoms and anxiety following surgery and medication interruption. Symptoms resolved after regular dopaminergic therapy was restarted.
• One high-dose participant experienced visual hallucinations five months after transplant following a medication change and a urinary tract infection. The episode resolved with medical management.
• One high-dose participant developed disseminated pulmonary aspergillosis with central nervous system involvement during active immunosuppression and died despite antifungal treatment and withdrawal of immunosuppression.

Investigators reported that none of the serious adverse events were attributed to the cell product or the surgical device. What really caught my attention, as this is on everybody’s mind… serial MRI scans showed no evidence of tumor formation or abnormal tissue growth during the 12-month follow-up.

A total of 373 non-serious adverse events were reported. Many were laboratory abnormalities linked to immunosuppression. The paper states that these events were generally manageable and consistent with the known safety profile of immunosuppressive therapy. No graft-induced dyskinesias were observed in the OFF state. One minor asymptomatic hemorrhage occurred during surgery in a single needle tract and resolved without sequelae.

Interim Imaging and Clinical Outcomes

Postoperative MRI confirmed accurate placement of all five injection tracts per hemisphere in each participant. Two participants showed MRI hyperintensities outside the graft site at 1 and 6 months that were interpreted as gliosis along the needle tract.

Interim PET imaging at 6 and 12 months showed focal increases in uptake in grafted regions in several participants, which investigators interpreted as evidence of cell survival. In the low-dose group, the putamen-to-caudate uptake ratio increased at 12 months by:

• 3.2% on the left side
• 5.7% on the right side

In the high-dose group, the ratio increased by:

• 14.9% on the left side
• 11.5% on the right side

The study reported a statistically significant difference in the right putamen-to-caudate ratio for the combined dataset, but not on the left side. Dopamine transporter PET imaging did not show significant differences at 12 months.

Preliminary motor findings were mixed. MDS-UPDRS part III OFF scores improved in three of four participants in the low-dose group and in one of three participants in the high-dose group between baseline and 12 months. Given the small sample size and early stage of the study, these results remain that way, preliminary.

Next steps coming soon from Cellular Intelligence…

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