Two Failures, One Success: Sanofi Announces Phase III Results of BTK Inhibitor Tolebrutinib in Multiple Sclerosis

▎Armstrong

On September 2, 2024, Sanofi announced the latest Phase III clinical advancements for the BTK inhibitor Tolebrutinib in treating multiple sclerosis. GEMINI 1 and GEMINI 2, for relapsing multiple sclerosis (RMS), did not meet the primary endpoint of Annualized Relapse Rate (ARR). HERCULES, for non-relapsing secondary progressive multiple sclerosis (nrSPMS), met its primary endpoint, becoming the first and only drug capable of delaying disability accumulation in nrSPMS patients.

Inflammation and immunology are Sanofi's most important business segments, while neuroimmunology is one of its key exploration areas, with a pipeline featuring multiple innovative drugs such as the BTK inhibitor Tolebrutinib, the CD40L antibody Frexalimab, and the RIPK1 inhibitor SAR443820.

Tolebrutinib has launched four Phase III clinical trials for multiple sclerosis, including GEMINI 1 and GEMINI 2 for the largest subtype RMS, HERCULES for nrSPMS, and PRESEUS for PPMS.

The patient population covered by RMS is 910,000 cases, the patient population covered by nrSPMS is 170,000 cases, and the patient population covered by PPMS is 120,000 cases.

Summary

Although the measure RMS is the broadest patient population, the Phase III clinical trial of Tolebrutinib for nrSPMS reaching its primary endpoint remains an important breakthrough. Last year, Novartis' BTK inhibitor opened the curtain for BTK to enter the autoimmune track with the CSU indication. In China, BeiGene's Zanubrutinib entered the autoimmune field starting with membranous nephropathy, while InnoCare Pharma's Orelabrutinib entered through indications such as lupus. Hansoh Pharma acquired the Chinese rights for non-oncology indications of LP-168, a BTK inhibitor from Lupeng Pharma, for 729 million yuan.