On day four of ADA 2021, eight cardiometabolic-related news items were observed from Bigfoot, AZ, Mannkind, Medtronic, Senseonics, BI/Lilly, Sanofi, and REMD Biotherapeutics. Below, FENIX provides context and analysis for the announcements, including thoughts on how the ALT increases observed in REMD’s Ph2 volagidemab trial could spell disaster in Ph3.
The CHMP agenda for this month (May 17-20) has been released, and it includes three notable items, EMPEROR-Reduced, DAPA-CKD, and vericiguat, as well as several other cardiometabolic-related entries. Below, FENIX provides highlights and insights from the respective news items.
A series of cardiometabolic-related news items have been observed: the CHMP agenda for this month’s meeting (February 22-25, 2021) has been released, and it includes one notable item: DAPA-CKD appears for the first time; and Gan & Lee announced a new partnership with IDF. Below, FENIX provides highlights and insights from the respective news items.
AstraZeneca announced FDA granted Priority Review to Farxiga for the treatment of chronic kidney disease in patients with and without T2DM based on results from the DAPA-CKD study. Recall, FDA previously granted Breakthrough Therapy designation to Farxiga for CKD in October 2020 following positive results from the DAPA-CKD trial which were first presented at ESC 2020. Of note, AZ stated the PDUFA date will occur in Q2 ’21. Below, FENIX provides a projected approval timeline for the impending DAPA-CKD regulatory review as well as readthrough to the SGLT2i class.
AstraZeneca (press release; slides), Provention Bio (press release), Teva (press release; slides), and Becton Dickinson (press release) hosted their respective Q3 ’20 earnings calls. Below, FENIX provides diabetes-related highlights and insights from the calls, including insight into AZ’s curious move to advance the development of its PCSK9i mAb.
Following the DAPA-CKD results, which were presented at ESC 2020 on August 30 (previous FENIX insight), AZ hosted a call with investors (view slides here). Beyond reviewing the DAPA-CKD results, AZ senior management and DAPA-CKD investigators provided commentary on the trial results and the new Farxiga market potential. Below, FENIX provides highlights from the investor call as well as additional perspective on the impact of DAPA-CKD.
Full results from the DAPA-CKD renal outcomes trial were presented at the 2020 virtual ESC conference (view AstraZeneca press release), but it does not appear the results have been published. Results demonstrated a highly impressive 39% RRR in the primary composite endpoint (sustained ≥50% decline in eGFR, ESKD, renal death, or CV death). Curiously, the CV death component of the primary endpoint failed to demonstrate a statistically significant benefit (HR=0.81; p=0.20); however, there was a statistically significant 31% RRR in all-cause mortality. Below, FENIX provides thoughts on the DAPA-CKD results in the context of the Invokana CREDENCE study (DKD), the ongoing EMPA-KIDNEY trial from BI/Lilly, and Lexicon’s SOLOIST and SCORED CVOTs.
AstraZeneca announced positive topline results from the Ph3 DAPA-CKD trial evaluating the effect of dapagliflozin on renal and CV outcomes in CKD patients with and without T2DM (view CT.gov record). According to the press release, Farxiga met all primary and secondary endpoints including all-cause mortality; however, no specific data was provided. Recall, DAPA-CKD was stopped at the end of March ~8 months early due to overwhelming efficacy (previous FENIX insight). Below, FENIX provides thoughts on the topline results ahead of the July 30 earnings call and in the context of the Invokana CREDENCE renal protection indication, the impending results from BI/Lilly’s EMPA-KIDNEY study, and Bayer’s FIDELIO-DKD outcomes trial for finerenone.
AstraZeneca hosted its Q1 ’20 earnings call and briefly discussed its diabetes business including the recent topline data readout from DAPA-CKD, which stopped early for overwhelming efficacy. Interestingly, AZ said it does not project DAPA-CKD filing acceptance until 2021. Below, FENIX provides highlights and insights from the call, including thoughts on why the DAPA-CKD submission is later than expected.
AstraZeneca announced that an independent data monitoring committee (DMC) has recommended stopping the DAPA-CKD study early due to overwhelming efficacy. According to CT.gov, the early trial closeout is ~8 months ahead of the full trial completion date (initially scheduled to complete in November 2020). Below, FENIX provides thoughts on DAPA-CKD in the context of Janssen’s CREDENCE, which was also stopped early, as well as potential read through to BI/Lilly and Lexicon.