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~30% relative risk reduction seen in symptomatic ischemic strokes in three milvexian arms compared to placebo; dose response not observed for primary study objective
No fatal bleeding and no increase in symptomatic intracranial hemorrhage observed in patients treated with milvexian, even with all patients receiving 21 days of background dual antiplatelet therapy followed by single antiplatelet therapy
Data from Phase 2 AXIOMATIC-TKR and -SSP studies collectively demonstrate potential of milvexian in thromboembolic diseases and warrant further investigation in Phase 3 studies
PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE:BMY) in collaboration with Janssen Pharmaceuticals, Inc., one of the Janssen Pharmaceutical Companies of Johnson & Johnson (Janssen), today announced results from the Phase 2 AXIOMATIC-SSP dose-ranging study of the investigational oral factor XIa (FXIa) inhibitor, milvexian, which showed an approximate 30% relative risk reduction in recurrent symptomatic ischemic strokes and favorable safety profile in three arms compared to placebo when used in combination with background antiplatelet therapy in patients with an acute non-cardioembolic ischemic stroke or transient ischemic attack.
The primary objective of this study was to detect a dose response for the composite endpoint of symptomatic ischemic stroke + MRI detected covert brain infarction across a 16-fold dose range; a dose response was not observed. A relative risk reduction of approximately 30% in symptomatic ischemic stroke with milvexian was observed in patients receiving either 25, 50 or 100 mg twice daily compared to placebo.
These data were presented today in a Hot Line session at the European Society of Cardiology (ESC) Congress 2022.
“Early stroke recurrence after ischemic stroke or transient ischemic attack (TIA) remains a significant risk despite advances in secondary prevention. Due to bleeding concerns, there are currently no anticoagulants used when a patient suffers an acute non-cardioembolic ischemic stroke; however, these data suggest that milvexian has potential to improve outcomes for stroke patients in clinical practice,” said Mukul Sharma, M.D. MSc, FRCPC, Director of the Stroke Program at McMaster University, Population Health Research Institute and Hamilton Health Sciences.i “The most important factor for stroke clinicians is the ability to reduce the risk of symptomatic ischemic stroke, and the AXIOMATIC-SSP study demonstrates this potential benefit with milvexian without increase of symptomatic intracranial hemorrhage or fatal bleeding.”
There was no increase in severe bleeding (e.g., symptomatic intracranial hemorrhage) versus placebo, and there was no fatal bleeding in any arm of the study, even with all patients on background dual antiplatelet therapy for 21 days followed by single antiplatelet therapy for the duration of the trial. The rate of major bleeding for milvexian 25 mg once daily and twice daily doses was similar to placebo, while a numerical increase was observed in milvexian dose arms of 50 mg twice daily and above, with no dose-response.
| Placebo | Milvexian | ||||
QD Regimen | BID Regimen | |||||
25 mg
| 25 mg
| 50 mg
| 100 mg
| 200 mg**
| ||
EFFICACY | ||||||
Evaluable Population | n = 625 | n = 308 | n = 287 | n = 306 | n = 277 | n = 317 |
Patients with composite event, % | 16.6 | 16.2 | 18.5 | 14.1 | 14.8 | 16.4 |
Symptomatic ischemic stroke | 6.1 | 4.9 | 4.2 | 4.2 | 4.0 | 8.5 |
Covert brain infarcts | 10.6 | 11.4 | 14.3 | 9.8 | 10.8 | 7.9 |
Relative Risk (RR) § |
| 0.99 | 0.99 | 0.93 | 0.92 | 0.91 |
95% CI for RR |
| (0.87, 1.10) | (0.84, 1.16) | (0.76, 1.17) | (0.73, 1.19) | (0.70, 1.32) |
ITT Population | n = 691 | n = 328 | n = 318 | n = 328 | n = 310 | n = 351 |
Symptomatic ischemic stroke incidence rate* | 5.5% | 4.6% | 3.8% | 4.0% | 3.5% | 7.7% |
Relative Risk (RR) |
| 0.83 | 0.69 | 0.72 | 0.65 | 1.40 |
95% CI for RR |
| (0.46, 1.49) | (0.36, 1.30) | (0.39, 1.33) | (0.33, 1.25) | (0.87, 2.25) |
SAFETY | ||||||
Treated Population | n = 682 | n = 325 | n = 313 | n = 325 | n = 306 | n = 344 |
Major (BARC Type 3 and 5) Bleeding |
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Composite event rate, n (%) [95% CI] | 4 (0.6) [0.2, 1.5] | 2 (0.6) [0.1, 2.2] | 2 (0.6) [0.1, 2.3] | 5 (1.5) [0.5, 3.6] | 5 (1.6) [0.5, 3.8] | 5 (1.5) [0.5, 3.4] |
Type 3, n (%) | 4 (0.6) | 2 (0.6) | 2 (0.6) | 5 (1.5) | 5 (1.6) | 5 (1.5) |
Type 5, n (%) | 0 | 0 | 0 | 0 | 0 | 0 |
*No hemorrhagic strokes occurred. **The 200 mg dose arm was not initiated at the beginning of the study; randomization to 200 mg occurred only after IDMC review of data concluded it was safe to add a higher dose. BARC = Bleeding Academic Research Consortium | ||||||
BARC Type 3 includes three subtypes: | ||||||
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