The Janssen Pharmaceutical Companies of Johnson & Johnson and Bristol Myers Squibb (BMS ) has reported that their experimental oral drug milvexian decreased the risk of postoperative venous thromboembolism (VTE) in the Phase II AXIOMATIC-TKR clinical trial in people undergoing total knee replacement (TKR) surgery.
An inhibitor of oral factor XIa, milvexian is being jointly developed by the companies.
The randomised, parallel-group, open-label, dose-ranging, multicentre trial analysed the efficacy and safety of milvexian as against subcutaneous dose of enoxaparin in subjects undergoing TKR surgical procedure.
It enrolled 1,242 subjects, who were categorised to receive one of seven regimens of oral doses of milvexian administered twice or once-daily or a 40mg subcutaneous dose of enoxaparin once every day.
The occurrence of total VTE up to 14 days was the trial’s primary efficacy outcome.
Any bleeding, which has been described as the combination of major, clinically significant nonmajor and minimal bleeding, was the key safety outcome.
Findings showed that the trial met both the pre-specified proof-of-principle criteria of the trial.
The dose-response for efficacy with a twice-daily dose of milvexian was significant. It was also found that the 12% VTE rate with combined twice-daily doses of milvexian was substantially lower compared with the 30% rate of the prespecified benchmark.
Milvexian provided a considerably reduced risk of VTE at daily dosages of a minimum of 100mg versus enoxaparin.
Furthermore, the milvexian treatment caused no major bleeds while one case was reported in the enoxaparin arm.
Milvexian and enoxaparin respectively led to 0.8% and 1.4% rates of major plus clinically relevant nonmajor bleeds.
Bristol Myers Squibb global drug development senior vice-president and cardiovascular development head Roland Chen said: “The clear dose efficacy response without increased bleeding provides additional evidence to support our belief in the promise of milvexian.
“We look forward to results from our second Phase II trial of milvexian for secondary stroke prevention, which will add to our body of evidence for milvexian and help inform our Phase III development program.”
Another Phase II trial of milvexian for secondary stroke prevention is underway with data anticipated in the first half of next year.