Roche Reveals Striking Data: 96% of Patients Did Not Relapse Within a Year, but Safety is in Doubt

Roche announced on September 4 the latest results from the Phase II FENopta Open Label Extension (OLE) study of the BTK inhibitor fenebrutinib. The results of the study showed that patients with relapsing multiple sclerosis (RMS) who received fenebrutinib for up to one year maintained extremely low levels of disease activity and did not experience disability progression. Roche plans to present the latest data from the FENopta-OLE study at the 40th session of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

Fenebrutinib is an oral, reversible, non-covalently bound BTK inhibitor that can effectively block the function of BTK. Preclinical studies have shown that fenebrutinib has significant activity and is highly selective, being 130 times more selective to BTK than other kinases. Currently, fenebrutinib is the only reversible BTK inhibitor in Phase III trials for the treatment of multiple sclerosis.

The FENopta study is a 12-week global, randomized, double-blind, placebo-controlled Phase II clinical trial designed to evaluate the efficacy, safety, and pharmacokinetics of fenebrutinib in 109 RMS patients aged 18 to 55 years. The primary endpoint was the number of new T1 lesions (T1-GD +) detected by brain magnetic resonance imaging (MRI) at weeks 4, 8, and 12, while secondary endpoints included the number of new/expanded T2 lesions detected by brain MRI at weeks 4, 8, and 12. And the proportion of patients with new T1-Gd+ lesions and new/enlarged T2 lesions at week 4, 8 and 12. T1 lesions are markers of active inflammation, while T2 lesions represent disease burden or lesion load.

Data from the 12-week study showed that fenebrutinib significantly reduced the number of new T1 lesions and new/enlarged T2 lesions compared to the placebo group. Of the patients who completed the FENopta study, 99 chose to continue participating in the Open Label Extension (OLE) study to receive fenebrutinib for up to 192 weeks.

During OLE, 96% of patients treated with fenebrutinib were disease free at one year, with an annualized recurrence rate (ARR) of 0.04, and disability remained stable at 48 weeks. MRI scans showed that fenebrutinib treatment effectively suppressed disease activity in the brain. At 48 weeks, 99% of patients had no T1-Gd+ lesions. Within 48 weeks of continued treatment with fenebrutinib, T2 lesion volume decreased by a factor of 3 compared to the end of the double-blind period (-0.33 cm3 vs -0.11 cm3).

The safety profile of Fenebrutinib in OLE is consistent with previously reported data. The most common adverse events (aes) in more than 5% of patients included urinary tract infections (8%), COVID-19 (7%), and pharyngitis (5%). One patient (1%) had a serious adverse event. Another patient (1%) had an asymptomatic elevation of alanine aminotransferase (ALT), which returned to normal after discontinuation.

There are currently three ongoing Phase III clinical trials of fenebrutinib, including the FENhance 1 and FENhance 2 studies in patients with RMS, and the FENtrepid study in patients with primary progressive multiple sclerosis (PPMS). Data from these studies are expected to be available by the end of 2025.

Levi Garraway, MD, Roche's chief medical officer and head of global product development, said: "After one year of treatment, our BTK inhibitor fenebrutinib was able to effectively inhibit virtually all disease activity and disability progression in patients with multiple sclerosis. If these results are confirmed in the ongoing Phase III study, fenebrutinib is expected to further improve the treatment landscape for patients with multiple sclerosis."

According to the information of the Medical Rubik's Cube database, a total of 4 BTK inhibitors are currently undergoing phase III clinical studies for multiple sclerosis in the world, and fenebrutinib is the only third-generation BTK inhibitor. The other three are evobrutinib (Merck), remibrutinib (Novartis) and tolebrutinib (Sanofi). In addition, there are three BTK inhibitors in Phase II clinical studies in multiple sclerosis, including obutinib (Norzenogenat), pitobutinib (Eli Lilly), and BIIB091 (Bogen).