After a prior phase 2 failure in CHANGE-MS showed signs of promise for progressive disease, the final patient visit has been completed in a trial of temelimab in relapsing disease, with results expected before the end of March 2022.
GeNuero announced that it has completed the phase 2a ProTEct-MS clinical trial (NCT04480307) of temelimab in patients with relapsing forms of multiple sclerosis (MS) who’ve been previously treated with rituximab. The final patient visit of the 1-year trial was completed on January 25, 2022.1
Topline results of the trial are expected to be reported out by the end of March 2022, according to GeNeuro.1 The double-blind, randomized controlled ProTEct-MS trial featured 40 participants at Karolinska Institeut we experienced disability progression without relapse, and randomized them to 3 different dose levels (18 mg/kg, 36 mg/kg, or 54 mg/kg) of temelimab or placebo to evaluate the safety, tolerability, and pharmacodynamic and pharmacokinetic (PD/PK) effects of the IgG4 antihuman endogenous retrovirus (HERV) monoclonal antibody, formally known as GNbAC1.
Previously, in the phase 2b CHANGE-MS trial (NCT02782858) and its long-term extension, ANGEL-MS (NCT03239860), temelimab did not meet the primary end point of reduction of the cumulative number of gadolinium-enhancing T1 lesions at 24 weeks, which the authors wrote “failed to show an effect on features of acute inflammation.” The results of the extension trial were presented at the 2019 European Committee for Treatment and Research in MS annual meeting by Hans-Peter Hartung, MD, PhD.2
ANGEL-MS featured 219 patients (94.8%) who had completed the first 48 weeks of CHANGE-MS. 75 patients, 68 patients and 77 patients enrolled to receive temelimab 6 mg/kg, 12 mg/kg and 18 mg/kg monthly IV infusions, respectively. All told, in the combined study periods, 18-mg/kg temelimab was associated with a 42% (P = .058) reduction in the atrophy rate of the cerebral cortex for those treated compared to the control group. Similarly, the reduction in the rate of atrophy of the thalamus was 43% (P = .038).In the 25-foot walk test, only 2.4% of patients the 18-mg/kg arm worsened 20% or more from baseline (P = .03), compared with 10.2% in the control group. Meanwhile, 23.1% and 13.3% of the 12-mg/kg and 6-mg/kg groups, respectively, worsened by 20% or more in the 25-foot walk test.2
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Although it failed to meet its primary outcome in phase 2b, Hartung et al added that “the results provide preliminary MRI evidence that temelimab could exert an antineurodegenerative effect based on measures of brain atrophy, myelin integrity, and number of chronic T1 hypointense lesions,” setting the stage for its development in progressive MS.3
“With the completion of patient visits in the ProTEct-MS trial, we now look forward to reporting out the efficacy and safety results by the end of March,” David Leppert, MD, chief medical officer, GeNeuro, said in a statement.1 “We would like to thank all the trial participants for their time and commitment to this important research effort, especially in the difficult circumstances of the past two years. We are also very grateful for the Karolinska/ASC team’s dedication and commitment as we now work towards the disclosure of the results.”
The therapy is also being developed against long-COVID, as data produced in 2021 suggested that SARS-CoV-2 derepresses the expression of the pathogenic protein HERV-W ENV in susceptible individuals,4 temelimab's main target in MS, which GeNeuro noted in its announcement “has well documented proinflammatory and pathogenic properties to nervous system cells. Its detection in COVID-19 patients provides a biological rationale for the use of GeNeuro’s temelimab as a novel therapeutic option against the long-term neuropsychiatric syndromes experienced by COVID-19 patients months after their infection.” The company noted that it plans to execute a phase 2 clinical trial, which is anticipated to start in the first half of 2022.
“Despite the continuing challenges posed by the COVID-19 pandemic, 2021 has been a key year for GeNeuro and the development of our HERV platform,” Jesús Martin-Garcia, CEO, of GeNeuro, said in a statement.1 “Having completed the last-patient’s last-visit yesterday for our ProTEct-MS trial at the Karolinska Institutet and the Academic Specialist Center (ASC) in Stockholm, Sweden, we confirm that results will be available by the end of March of this year. This will of course be a key milestone for the company and for MS patients.”