Enrollment start H2 2021. Could be July, could be December. Pending COVID-19 issues. Most likely late 2021 to start enrollment. They want to complete 3600 patient enrollment within 4 months. This seems ambitious based on how long it took them to get 2400 for BETonMACE. However, they are relaxing the recent ACS timeline to allow for ACS event within 7 to 180 days (potentially longer if FDA opinion allows) instead of within 7 to 90 days before. So this may help speed enrollment. Hopefully they can do it. If enrollment starts late 2021 then enrollment could theoretically be complete by Q1 2022.

Patients. The proposed 3600 patients in BETonMACE 2 is ~1.5 times the size of BETonMACE patient population (2425 pateints). Only ~290 of the patients were CKD (eGFR betwen 30 and 60) in BETonMACE. All patients in BETonMACE2 will be T2D and CKD with baseline eGFR between 20 and 60, and low HDL. Additionally, it is estimated that 70% in BETonMACE2 will be on an SGLT2i; only ~12.5% were on SGLT2i in BETonMACE. However, I wasn't able to tease out how many CKD patients in BETonMACE were on SGLT2i. Not clear if only using one SGLT2i or allowing different SGLT2i. SGLT2i won't be required for all BETonMACE2 patients, but will be mandated if clinically indicated. 

Primary Endpoints look good. Keeping cardiovascular death and non-fatal myocardial infarction as in BETonMACE , but dropping non-fatal stroke. Adding in hospitalization for congestive heart failure. This is well informed by BETonMACE data. Looking for 600-650 total events as opposed to the 250 of BETonMACE. No info on secondary endpoints or pre-specified subgroups yet. Interim analysis at 300 events. 90% power for a hazard ratio of 0.78 (22% relative risk reduction). Keep in mind that the SGLT2i and CKD sub-groups had RRRs in the 50-70% range. However, these sub-group post-hocs were based on small patient populations.

Timeline to reach endpoints. Based on the high event rate in the CKD population, they estimate that they will reach 300 events (50% of total target events) within 4 months of completing enrollment. At this point, they plan an interim analysis. Pending interim analysis success, FDA approval is possible due to the Breakthrough Therapy Designation. So if enrollment starts late 2021, and if enrollment completes in Q1 2022, then it is possible to be at this point by mid 2022. Note: possibility and probability are two different animals. Lots of moving parts. Of course, if the interim analysis fails and they continue the trial then timelines will be extended to reach the original number of planned events.

For reference, here is the detailed Nov 2019 BETonMACE presentation. 

https://www.resverlogix.com/upload/media_element/202/0fe84959b9a4/betonmace-post-aha-presentation-final.pdf

The plan to reformulate apabetalone into tablet form, as well as in a time release format to allow once a day administration sounds promising too. However, these chemistry upgrades will be done in parallel and do not need to be complete before start of BETonMACE2 trial. 

Not sure how long this link will last, but for now here is direct link to yesterdays's slides.

http://118009.choruscall.com/resverlogix/resverlogix20210204.pdf

BDAZ