New drug for multiple sclerosis (MS)! CNS osmotic covalent BTK inhibitor evobrutinib: 3.5 years of treatment, showing long-lasting clinical benefits!

BIOON, Oct.
31, 2022 /BioValley/ -- Merck KGaA recently announced the results of a clinical study at the 38th European Congress on Multiple Sclerosis Treatment and Research (ECTRIMS 2022).
The data showed that the annual recurrence rate (ARR) remained low and the Extended Disability Status Scale (EDSS) score remained stable
in patients with recurrent multiple sclerosis (RMS) treated with evobrutinib, a highly selective oral central nervous system (CNS) permeable covalent BTK inhibitor evobrutinib for more than 3.
5 years.
In addition, the number of T1 gadolinium-enhanced (Gd+) foci and T2 lesion volume remained low
during the open-label expansion (OLE) of Phase 2 clinical trials.
These data demonstrate the long-term positive benefits
of evobrutinib as a potential best-in-class therapy for RMS patients.

Multiple sclerosis (MS) is a chronic inflammatory central nervous system disease that is the most common non-traumatic, disabling neurological disease
in young people.
It is estimated that approximately 2.
8 million people worldwide have MS
.
While symptoms can vary, the most common symptoms of MS include blurred vision, numbness or tingling in the limbs, and problems with
strength and coordination.
The type of recurrence of multiple sclerosis is the most common
.

evobrutinib is an oral, highly selective, central nervous system (CNS) osmotic immunomodulator that has the potential to be a safe and highly effective RMS treatment option by inhibiting Bruton's tyrosine kinase (BTK) signaling in B cells and microglia and addressing peripheral and central drivers of inflammation
.
Evobrutinib's two-sided approach can better control the silent progression of the disease between disease onset in RMS patients, while also effectively controlling recurrence
.

Evobrutinib chemical structure (Image source: bjbalb.
com)

The open-label extension (OLE) section of the Phase II clinical trial evaluated the long-term therapeutic effect of evobrutinib on ARR, EDSS scores and several magnetic resonance imaging (MRI) results in RMS patients: throughout the course of OLE, the ARR remained low at
0.
13 in patients who initially took 75 mg orally twice daily.
In addition, in patients who changed from 75 mg once daily to 75 mg twice daily in OLE, the ARR decreased from 0.
19 to 0.
09
.

Overall, mean EDSS scores and MRI injury activity remained low and stable
throughout the study.
These data points further strengthen the previous observation that the maximum BTK share achieved over the entire dosing interval achieved by 2 dosing per day is associated
with a higher ARR reduction in evobrutinib.

New long-term data from the OLE portion of the Phase II clinical trial found reduced levels of blood neurofilament light chains (NfL), a key biomarker that predicts future brain volume loss and disease progression
.
Compared to the double-blind phase (DBP) and OLE baseline, blood NfL levels continued to decrease
.
The 75 mg dose twice daily significantly reduced NfL levels
compared to placebo/evobrutinib 25 mg once daily from week 12 (DBP).
Reduced NfL levels provide evidence that evobrutinib can reduce neuronal damage
in RMS patients.

The latest data from post-hoc analysis of patients (n=24) vaccinated against COVID-19 during phase 2 OLE were also presented at the meeting, showing that 96% of RMS patients treated with evobrutinib (75 mg twice daily) were able to develop an antibody response after receiving 2 doses of mRNA new coronavirus vaccine, similar
to untreated RMS patients and healthy subjects.
Increased antibody responses in seronegative and seropositive patients indicate that the response to neoantigens and memory antigens remains unchanged
.
This is the first time this has been shown in a BTK inhibitor in RMS, and the findings are consistent with the regulation of B cell function, providing a potential alternative treatment
for the B cell depletion approach.

Jan Klatt, senior vice president, head of neurological and immunology development at Merck, said: "This is the first time that BTK inhibitors have been used in RMS to show efficacy
lasting three and a half years.
Combined with our previously published data on a decrease in volume of slowly dilated lesions (SEL), effects on microglia, and reductions in neurofilament levels (markers of nerve damage), we believe evobrutinib has the potential to deliver best-in-class efficacy
to RMS patients.
" (Bio Valley Bioon.
com)

Merck Highlights New Data for Evobrutinib, First BTKi to Demonstrate Sustained Clinical Benefit for People with RMS through Three and a Half Years of Treatment