Sanofi Innovative Parkinson's Disease Drug Fails in Phase 2 Clinical Trials

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Sanofi Innovative Parkinson’s Disease Drug Fails in Phase 2 Clinical Trials

Parkinson’s Disease (PD), a complex neurodegenerative disorder, ranks as the second most common neurodegenerative disease worldwide, following Alzheimer’s Disease (AD).

It affects approximately 1%-2% of individuals aged 65 and above. With the global aging population, the prevalence of Parkinson’s Disease is expected to significantly increase.

Sanofi Innovative Parkinson's Disease Drug Fails in Phase 2 Clinical Trials

Currently, over 6 million people worldwide suffer from Parkinson’s Disease, with approximately 60,000 new diagnoses each year. PD results from the loss of dopamine-producing neurons in the brain, impacting both movement and cognition and causing symptoms such as tremors, muscle stiffness, confusion, and dementia.

About 10% of Parkinson’s Disease cases are linked to mutations in the GBA1 gene, although the precise cause of Parkinson’s Disease in individuals with this mutation remains unclear. Those with GBA1 gene mutations may experience a more aggressive disease course.

GBA1 is known to regulate the production of glucocerebrosidase, a crucial enzyme for lysosomal function. Its deficiency leads to the accumulation of glucosylceramide, one of its substrates, causing lysosomal dysfunction. Preclinical data have suggested that reducing glucosylceramide levels could have a positive impact on Parkinson’s Disease.

Previously, Sanofi developed an oral glucosylceramide synthase (GCS) inhibitor called venglustat, which has the potential to traverse the blood-brain barrier and treat Parkinson’s Disease.

Recently, researchers at Sanofi published a study in The Lancet Neurology titled “Safety and efficacy of venglustat in GBA1-associated Parkinson’s disease: an international, multicentre, double-blind, randomised, placebo-controlled, phase 2 trial.”

Parkinson’s Disease is not a monogenic disorder, but several distinct genetic variations are associated with an increased risk of the disease, with GBA1 gene mutations being highly correlated.

This study represents the first truly personalized therapy for Parkinson’s Disease, and in this international, multicenter, double-blind, randomized, placebo-controlled Phase 2 clinical trial, venglustat failed to demonstrate therapeutic efficacy in patients with GBA1 gene mutations associated with Parkinson’s Disease.

In this Phase 2 clinical trial, 221 Parkinson’s Disease patients with GBA1 gene mutations from 52 different medical centers worldwide received either venglustat or a placebo once a week for one year. The results indicated that venglustat was safe, with only mild side effects, but it did not show therapeutic benefits for Parkinson’s Disease patients.

The research team noted that the drug did indeed lower glucosylceramide synthase (GCS) levels, but the ultimate therapeutic effect remained elusive.

This well-designed and executed clinical study suggests that inhibiting glucosylceramide synthase (GCS) might not be the way to treat Parkinson’s Disease in patients with GBA1 gene mutations.

However, it does not discount the association between GBA1 gene mutations and Parkinson’s Disease. Future efforts may explore alternative approaches to target GBA1 in treating this condition.

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