#AAN2022 – Long-term Evobrutinib Safe, Effective in Relapsing MS

Long-term treatment with evobrutinib safely and effectively reduces the rate of relapses in adults with relapsing forms of multiple sclerosis (MS), according to 2.5 years of data from a Phase 2 extension study.

These findings — supporting evobrutinib’s therapeutic potential in relapsing MS — were shared in an oral presentation at the 2022 American Academy of Neurology (AAN) Annual Meeting, being held in person April 2–7 in Seattle, and virtually April 24–26.

“We are working tirelessly on the future of MS treatments with evobrutinib, which targets both acute and potentially also chronic inflammation to prevent disease progression and achieve better outcomes for patients,” said Jan Klatt, MD, senior vice president and head of development unit neurology and immunology at Merck KGaA, the therapy’s developer (known as EMD Serono in North America).

“With new evobrutinib data at AAN, we now have two and a half years of efficacy and safety data in patients with relapsing MS from the largest Phase 2 BTK inhibitor clinical trial,” Klatt added.

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Evobrutinib works by blocking the activity of Bruton’s tyrosine kinase (BTK), a protein involved in the activation of certain types of immune cells in the body. These cells, particularly B-cells, drive inflammation and the abnormal immune attacks that damage the nervous system in MS.

The therapy, given as an oral tablet, is expected to slow or halt further neurodegeneration in people with MS.

An earlier Phase 2 clinical trial (NCT02975349) had evaluated evobrutinib’s safety and effectiveness in 267 adults with relapsing MS, including relapsing-remitting MS and active secondary progressive MS.

Participants were randomly assigned to receive either evobrutinib — in one of three regimens, specifically 25 mg once daily, 75 mg once daily, or 75 mg twice daily — a placebo, or Biogen’s approved MS therapy Tecfidera (dimethyl fumarate).

All regimens were given for 48 weeks (nearly one year), except for the placebo, which was administered for 24 weeks and followed by evobrutinib (25 mg once daily) for the remaining 24 weeks.

Top-line results showed that the experimental therapy was generally safe at all three doses and that its highest dose (75 mg twice daily) worked better than a placebo at reducing both inflammatory brain lesions and annualized relapse rates. The results specifically showed 0.11 relapses per year for the high dose after 48 weeks versus 0.37 for the placebo group after 24 weeks (about six months).

Also, 79% of patients in this highest dose group remained relapse-free after nearly one year of treatment.

A total of 213 patients (80%) who completed the trial chose to enroll in its open-label extension (OLE) study, in which all are receiving evobrutinib at 75 mg once daily for 48 weeks followed by 75 mg twice daily.

Previous data from the Phase 2 trial and its OLE study showed that the therapy’s benefits were sustained for two years.

The newly announced data concerned the 164 patients (61%) who completed at least 132 weeks (about 2.5 years) of treatment in the OLE study. For those initially assigned to evobrutinib, the total treatment time was 180 weeks or nearly 3.5 years.

Results of the OLE study were shared in an oral presentation, titled “Safety and Efficacy of Evobrutinib, a Bruton’s Tyrosine Kinase Inhibitor in Relapsing Multiple Sclerosis Over 2.5 Years of The Open-Label Extension to a Phase II Trial.”

Overall, the annualized relapse rate remained low (0.12 relapses per year) during the 2.5 years in the OLE for patients assigned to the highest dose of evobrutinib in the Phase 2 study.

Also, the therapy continued to be generally safe and well-tolerated, with no new safety concerns identified. Adverse events were reported in 77.5% of patients, and considered related to evobrutinib in 27.7% of patients. Six serious adverse events were treatment-related. Severe infections were reported in nine (4.2%) patients; three of them were fatal, but deemed unrelated to the therapy.

More than two years into the OLE study, more than 81% of patients had normal levels of antibodies, which are produced by B-cells. That proportion was found despite B-cell counts being maintained at low levels for at least up to 96 weeks (nearly two years).

Increases in the levels of liver enzymes, suggestive of liver damage, were reported in the first three months of OLE, but only in patients given 25 mg of evobrutinib or Tecfidera in the main trial.

Higher-than-normal levels of enzymes, indicative of pancreatic inflammation, were detected in a low proportion of patients, but were not associated with clinical signs or symptoms.

“Evobrutinib safety and efficacy data over 2.5 years [in the OLE study] continue to show acceptable tolerability, with no new safety signals, and maintained efficacy,” in people with relapsing MS, the researchers wrote.

The therapy is now being tested in more than 1,800 adults with relapsing forms of MS in two identically designed Phase 3 trials — EVOLUTION RMS 1 and 2 (NCT04338022 and NCT04338061) — whose top-line data are expected in late 2023.

Note: The Multiple Sclerosis News Today team is providing coverage of the American Academy of Neurology (AAN) 2022 Annual Meeting. Go here to see the latest stories from the conference.