June 4, 2023

Watch on Radcliffe Cardiology:

Hi my name is manash patel i’m the chief of cardiology and co-direct the heart center at duke university and i’m an investigator at the duke clinical research institute you know we have patients with atrial fibrillation and we’ve had advances in the anticoagulation of our patients we’ve gone from warfarin to doax or direct acting oral anticoagulants such as

Apixaban or rivaroxaban but we still have patients with unacceptable bleeding and a lot of patients who don’t get therapy so the background to the study is are there new therapies that we could use in patients like that and asyndexion is a new small molecule that inhibits factor 11 and it was studied in pacific af pacific af is a phase 2 study and it’s looking

At understanding the dosing of asyndexion a small molecule that inhibits factor 11 and is minimally renally cleared we used 20 milligrams and 50 milligrams once daily vasandexian and compared it to a pixivan with standard dosing in 750 patients with atrial fibrillation we followed them for about three months to see what the rates of bleeding were the reason we’re

Looking at bleeding is to understand the dosing relationship with asyndexion and apixaban for bleeding as we get ready to do a large phase three outcome study it’s important to recognize a lot of ways can be evaluated to see how patients bleed and this was done during the covet time the patients were patients with atrial fibrillation and a chad’s too vast score of

About four many of them had some renal dysfunction many co-morbidities heart failure diabetes there were 48 total bleeding events and even though isth major and non-clinically non-major clinically relevant bleeding was the primary safety evaluation and what we found is both doses of asyndexion had less bleeding than a pixaban about 50 less small numbers but at least

Encouraging to show us that there is seems to be a safety profile for the therapy currently i don’t think these findings can affect clinical practice because the therapy’s still being evaluated pacific af is one of three studies there’s an ami study and a stroke study and through that we’ll learn about the dosing of the drug as we get ready for large phase three

Studies together so these phase two studies will help us what’s important though is that we want to engage patients so we are doing something called pearl af people can go to afib opportunities.com and later this spring participate and tell us what matters for them if they have atrial fibrillation are they interested in being in the study we hope that these types

Of trials and agents will tell us in the future how to get to a better place for our patients with atrial fibrillation yeah the critical next step is to actually design phase three or outcome studies that engage more people more women more underrepresented patients more patients from around the world that previously have not been in trials and hopefully develop

Ways in which these therapies work across those broad populations to increase the adoption of new therapies i think we all know that many patients with atrial fibrillation have a risk of stroke and systemic embolism currently clinically we don’t treat them because of a bleeding risk the take-home message of this is factor 11 assay has shown us that asyndexion

Inhibits 90 of factor 11 activity and at that rate we have looks like 40 to 50 percent of the bleeding of a pixel band so encouraging for the phase 3 data you

Transcribed from video
ACC 22: Results from the PACIFIC AF Trial | Dr Manesh Patel By Radcliffe