Further, at daily doses of at least 100 mg, the rates of VTE with milvexian were significantly lower than with enoxaparin, according to the study authors.
Results from the phase 2 AXIOMATIC-TKR study showed the investigational oral drug milvexian reduced the risk of postoperative venous thromboembolism (VTE) in a dose-dependent manner without increasing the risk of bleeding compared with enoxaparin in patients undergoing total knee replacement surgery (TKR), according to a Johnson & Johnson press release.
“This study establishes proof-of-principle for milvexian as a differentiated antithrombotic agent,” said Jeffrey Weitz, MD, professor of Medicine & Biochemistry and Biomedical Sciences at McMaster University, in the press release. “Furthermore, the consistently low rates of bleeding across a 16-fold range of milvexian doses suggest that it has a wide therapeutic window, which opens the opportunity to explore milvexian across a broad range of patients including those for whom factor Xa inhibitors are underutilized or not indicated.”
The trial met both of its requirements, with the dose response for efficacy with twice-daily milvexian found to be significant and the 12% rate of VTE with combined twice-daily doses of milvexian being significantly lower than the prespecified benchmark rate of 30%. Further, at daily doses of at least 100 mg, the rates of VTE with milvexian were significantly lower than with enoxaparin, according to the study authors.
The study also found no major bleeds with milvexian and 1 with enoxaparin. The rates of major plus clinically relevant nonmajor bleeds with milvexian and enoxaparin were 0.8% and 1.4%, respectively. Additionally, across a 16-fold range of doses, milvexian demonstrated a low risk of major plus CRNM bleeding with no major bleeds and no dose-response on this composite outcome.
“These promising phase 2 data support a profile that is consistent with better efficacy and safety than enoxaparin and reinforce our confidence in milvexian,” said James List, MD, PhD, Global Therapeutic Area Head, Cardiovascular, Metabolism, & Retina, Janssen Research & Development, LLC, in the press release. “We’re optimistic about the milvexian program and its potential impact for patients.”
This study is the first of 2 from the phase 2 milvexian program, with results from the ongoing phase 2 study of milvexian for secondary stroke prevention expected in the beginning of 2022.
Late-Breaking Phase 2 Data for Investigational Oral Factor XIa Inhibitor Milvexian Suggest Favorable Antithrombotic Profile Across a Wide Range of Doses. Johnson and Johnson. November 15, 2021. Accessed November 16, 2021. https://www.jnj.com/late-breaking-phase-2-data-for-investigational-oral-factor-xia-inhibitor-milvexian-suggest-favorable-antithrombotic-profile-across-a-wide-range-of-doses