Sanofi Discontinues Venglustat in Parkinson’s Disease and Multiple Mid-Stage R&D Programs

Compiled by Fan Dongdong

Biogen is not the only large biotech company to encounter obstacles in Parkinson’s disease trials. Recently, Sanofi disclosed in its year-end earnings report that it had decided to suspend its Phase II development program for neurodegenerative diseases. Two days later, Sanofi announced in its earnings release that it would terminate the Phase II trial of venglustat, its investigational Parkinson’s disease drug.

Previously, Sanofi believed that venglustat could reduce glucosylsphingolipid (GSL) levels in patients’ plasma and cerebrospinal fluid, holding greater promise as the first innovative therapy to modify the disease course in this type of Parkinson’s disease.

However, according to the latest news, Sanofi announced in late January that its Phase II clinical trial of venglustat for Parkinson’s disease, which enrolled 270 participants, had failed. Nevertheless, the company stated that it would continue to investigate the potential efficacy of venglustat, a glucosylceramide synthase (GCS) inhibitor, in a limited number of rare diseases, including polycystic kidney disease, Tay-Sachs disease, and Gaucher disease. Researchers have found that in Parkinson’s disease patients with mutations in the gene encoding glucocerebrosidase (GBA), the deficiency of GBA leads to the accumulation of glycosphingolipids (GSLs) in the brain, which in turn triggers the aggregation of α-synuclein.

Sanofi had previously anticipated that venglustat could inhibit the production of alpha-synuclein in this patient population, thereby achieving therapeutic efficacy. However, despite robust preclinical evidence, venglustat ultimately failed to meet the primary endpoint of the trial, leading to the termination of its development.

This move is also part of CEO Paul Hudson’s strategy to continue phasing out non-core product lines and drive reforms in the company’s R&D structure and strategic direction. In December 2019, Hudson announced that Sanofi would concentrate its efforts and resources on developing six key priority programs, gradually shifting its R&D focus toward oncology, immunology, and rare diseases. On this occasion, Sanofi also disclosed certain changes to its mid-term pipeline, including the discontinuation of the development of romilkimab, an anti-IL-4/IL-13 bispecific monoclonal antibody, for systemic sclerosis. Furthermore, the development of itepekimab, an anti-IL-33 therapy, for asthma will no longer proceed, and the program evaluating the combination of isatuximab and cemiplimab for the treatment of lymphoma has also been terminated.

According to Sanofi’s 2020 annual financial report, net revenue reached €36.041 billion, a year-on-year decrease of 0.2%. In 2020, revenue from the Pharmaceuticals division amounted to €25.674 billion, a year-on-year increase of 3.1%; revenue from the Vaccines division reached €5.973 billion, a year-on-year increase of 8.8%; while revenue from the Consumer Healthcare division showed no net growth, amounting to €4.394 billion, a year-on-year decrease of 1.9%.

Among Sanofi’s entire product portfolio, Dupixent is undoubtedly the most prioritized asset. In 2020, global sales of Dupixent continued to achieve robust growth, driven by clinical demand in adult and adolescent atopic dermatitis. Last May, the indications for Dupixent were further expanded with approval for use in children aged 6 to 11 years with atopic dermatitis. Coupled with its presence in the asthma and chronic rhinosinusitis with nasal polyps markets, Dupixent’s sales revenue surged by 70% in 2020. Just four years after its launch, cumulative sales reached €3.534 billion, positioning the drug to meet Sanofi’s previous forecast of peak annual sales exceeding €10 billion.

Furthermore, the approval of Dupixent for marketing in China and its successful inclusion in the National Reimbursement Drug List have created favorable conditions for striving toward this goal. In addition, Sarclisa (isatuximab), an oncology drug developed by Sanofi, received approval from the U.S. Food and Drug Administration in March 2020. As the second CD38 monoclonal antibody launched globally, it is indicated as a third-line therapy for the treatment of multiple myeloma. In 2020, Sarclisa generated sales revenue of €43 million.

Reference Source:

1.Sanofi flunks Parkinson's Phase II, axes handful of mid-stage programs in Q4 earnings

2.Sanofi Q3 2020 business EPS growth of 8.8% at CER