October 13, 2023
Roche Reveals Promising Data on Fenebrutinib in Relapsing Multiple Sclerosis
Roche presented the Phase II FENopta study, shedding light on the potential of the investigational BTK inhibitor, fenebrutinib, in treating relapsing multiple sclerosis (RMS). The data showed that fenebrutinib not only penetrates the blood-brain barrier but also significantly reduces brain lesions in RMS patients, all while maintaining a consistent safety profile observed in previous fenebrutinib trials involving over 2,500 participants.
The ability of fenebrutinib to cross the blood-brain barrier is a significant finding, suggesting its potential to directly address the chronic inflammation associated with multiple sclerosis (MS). In a subgroup of 11 RMS patients, cerebrospinal fluid (CSF) analysis revealed a mean fenebrutinib concentration of 43.1 ng/mL after 12 weeks of continuous treatment.
Moreover, fenebrutinib demonstrated remarkable efficacy in reducing brain lesions associated with RMS.
This reduction was notably rapid, with a 92% reduction in new T1 gadolinium-enhancing (T1 Gd+) lesions and a 90% reduction in new or enlarging T2-weighted (T2) lesions observed after eight weeks of treatment. The benefits extended further, with relative reductions of 90% in T1 Gd+ lesions and 95% in T2 lesions noted at 12 weeks.
Notably, the safety profile of fenebrutinib remained consistent with previous clinical trials. Adverse event rates were 38% for the fenebrutinib group and 33% for the placebo group.
Fenebrutinib, the non-covalent and reversible BTK inhibitor in Phase III trials for MS, was meticulously designed for high selectivity.
This selectivity may contribute to the drug's efficacy while minimizing off-target effects, potentially resulting in improved long-term safety outcomes.
Currently, an open-label extension of the FENopta study is underway. Phase III studies are actively enrolling participants, including FENhance 1 and 2 for RMS patients and FENtrepid for primary progressive MS (PPMS) patients.
October 11, 2023
Roche presented non-inferior data of Ocrevus SC versus Ocrevus IV; Roche aims to bring twice-yearly SC formulation to patients.
Roche has unveiled groundbreaking findings from the Phase III OCARINA II study, introducing Ocrevus (ocrelizumab), a novel subcutaneous injection with the potential to revolutionize the treatment of multiple sclerosis (MS) by offering a swift and convenient option for patients. The study assessed the impact of this new 10-minute subcutaneous injection, administered twice a year, on pharmacokinetic, biomarker, and MRI measures among individuals with relapsing or primary progressive MS (RMS or PPMS).
The study's key revelation was that Ocrevus subcutaneous injection proved non-inferior to the existing intravenous (IV) infusion method regarding Ocrevus levels in the patient's blood over the initial 12 weeks.
The subcutaneous injection of Ocrevus resulted in rapid, sustained, and near-complete depletion of B cells, mirroring the outcomes of Ocrevus IV infusion. At the 14-day mark, 97% of subcutaneous injection patients and 98% of IV infusion patients had B cell levels of 5 cells/µL or less, a trend that persisted over 24 weeks.
Both delivery methods also exhibited a remarkable capacity for suppressing MRI lesion activity. By the 24-week mark, nearly all patients in both groups displayed no T1 gadolinium-enhancing (T1-Gd+) lesions, indicative of active inflammation, and no new/enlarging T2 lesions, representing the disease burden or lesion load.
24 week adjusted lesion rate
New/enlarging T2 lesions; 24-week adjusted lesion rate
The OCARINA II study results will be submitted to health authorities worldwide in the coming months.
October 11, 2023
BMS presented long-term data on Zeposia; 47% of patients showed improvement in cognitive functioning after one year of treatment.
Bristol Myers Squibb has released new data on the long-term disease progression and cognitive function in Zeposia treated patients with relapsing forms of multiple sclerosis. These insights are derived from the DAYBREAK and RADIANCE trials, which exhibit consistently low progression-independent relapse activity (PIRA) rates and relapse-associated worsening (RAW) after eight years of Zeposia treatment.
Furthermore, an interim analysis of the Phase 3b ENLIGHTEN trial, focusing on patients with early RMS, reveals significant findings.
Almost half of these patients (47.4%) showed clinically meaningful improvements in cognitive functioning after one year of Zeposia treatment, defined as an increase of at least four points or 10% from baseline according to the symbol digital modalities test (SDMT). Notably, most patients (91.9%) displayed minimal clinical or radiologic evidence of RMS disease activity during this timeframe.
Additionally, the study evaluated treatment-emergent adverse events (TEAEs), identifying COVID-19 as the most frequent TEAE, with other common TEAEs consistent with those reported in the broader Zeposia clinical development program.
These results provide valuable insights into the sustained efficacy of Zeposia in treating relapsing multiple sclerosis and its potential to enhance cognitive functioning in RMS patients. These findings were presented at the 9th Joint ECTRIMS-ACTRIMS meeting in Milan, Italy.
Other trials that BMS highlighted were:
DAYBREAK: Phase 3 study that involves a prolonged open-label extension, focusing on evaluating the safety and effectiveness of Zeposia (ozanimod) when administered orally to individuals dealing with relapsing forms of multiple sclerosis.
RADIANCE: A pivotal Phase 3, multicenter, double-blind, double-dummy, active-controlled trial that compared the efficacy, safety, and tolerability of oral Zeposia to intramuscular Avonex in RMS patients.
SUNBEAM: Another pivotal Phase 3, multicenter, double-blind, double-dummy, active-controlled trial, which evaluated the efficacy, safety, and tolerability of two doses of oral Zeposia against intramuscular Avonex in RMS patients.
ENLIGHTEN: A Phase 3b, open-label study that measures changes in cognitive processing speed using the symbol digital modalities test in RMS patients treated with oral Zeposia.