The results of the longest follow-up of any inhibitor drug.
Multiple Sclerosis (MS): Microglia cells (orange) damage the myelin sheath of neuronal axons, leading to a loss of nerve function. Photo: Shutterstock.
Evobrutiniba tyrosine kinase inhibitor (BTK) of Bruton in research for multiple sclerosis recurring (EMR), is relatively safe and effective in the long term, new research suggests.
Results from the longest follow-up of any BTK inhibitor drug for MS to date show efficacy of more than two and a half years in slowing the neurodegeneration of the disease.
The findings are presented here at the Annual meeting 2022 of the Consortium of Multiple Sclerosis Centers (CMSC).
Initially developed for cancer, BTK inhibitors are highly anticipated drugs in MS due to their ability to provide a more specific approach in inhibiting hyperreactive B cell responses that cause inflammation without directly affecting T cells or healthy B cells, which can occur with other anti- Medicines CD20.
“Los evobrutinib mechanisms of action and others BTK inhibitors are attractive because they affect both B cells and microglial cells, in ways that might suggest they might be similar to or perhaps better than anti-CD20 monoclonal antibodies,” said Wolinsky.
Previous data from the ongoing phase 2 trial of evobrutinib have been promising. As reported by Medscape Medical Newsthe data published in the New England Journal of Medicine in 2019 showed that the oral drug was well tolerated and associated with reductions in acute inflammation and chronic and a reduction in T1 gadolinium-enhancing lesions in RMS versus placebo at week 24.
The ongoing study, which is said to be the largest phase 2 study of any BTK inhibitor in MS and the longest study at 2.5 years, included 267 patients with RMS or multiple sclerosis Multiple secondary progressive.
The study began with a 48-week double-blind period in which patients were randomly assigned to receive evobrutinib as an oral tablet 25 mg or 75 mg once a day; 75 mg twice daily, or open-label dimethyl fumarate (DMF; 240 mg twice a day); or placebo. At week 24, he was switched to evobrutinib 25 mg once daily.
no red flags
In the latest update of the open-label period up to 2.5 years, the investigators report that the 75 mg twice daily dose (n = 42) was associated with annualized relapse rate (ARR) more low. The ARR was 0.12 for patients who had originally received 75 mg once daily. day in double period blinded versus an ARR of 0.3 in the placebo group.
Disability, assessed with the Scale of extended disability status, was stable through week 144 in the open-label extension in patients treated with evobrutinib.
Importantly, the treatment continued to show relative safety, with treatment-emergent adverse events (TEAEs) reported among 77.5% of patients. Evobrutinib-related TEAEs occurred in 27.7%.
There were also six serious TEAEs that were determined to be related to treatment. Nine patients (4.2%) reported grade 3 or higher serious/opportunistic infections, three of which were fatal. However, these were not considered related to therapy.
There were also two cases of COVID-19 pneumonia and one case of E coli sepsis, both of which were considered unrelated to treatment.
TEAEs were generally described as mild or moderate in the open-label extension period, with no dose-dependent increase in TEAEs among patients who switched to evobrutinib 75 mg twice daily.
At week 120 of the open-label period, most participants had normal Ig levels, including IgG (91%), IgA (88%), and IgM (82%).
At the start of the open-label period, 13% of patients had low B-cell counts. At week 96, 52% had low B-cell counts and the remaining 48% had normal counts.
ALT/AST liver enzyme elevations were seen only among those who had received DMF or evobrutinib 25 mg and occurred within 12 weeks of the open-label extension.
Amylase increases, related to pancreatic damage, occurred in six (2.8%) patients and lipase increases in 24 (11.3%) patients, but without clinical signs or symptoms.
Wolinsky noted that while it’s “too early to be sure, there are no unusual safety concerns so far” with the drug.
“As MS specialists, we are always interested in novel approaches to managing the disease process that might have the potential for better efficacy, safety or compliance than existing drugs or [para] possibly help fill in the gaps for hard-to-control specific treatments,” cases.
Of course, “one must first rigorously show what the currently attractive possibilities are,” Wolinsky said.
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