Coming on the heels of the European Society of Cardiology 2023 Congress, one might have expected September 2023 to be a quieter month for the cardiology community. However, this would not be the case as September 2023 would feature a slew of significant pipeline updates, in the form of new trial data, FDA advisory committee meetings, and other regulatory decisions.
In our September 2023 cardiology month in review, the editorial team of HCPLive Cardiology highlights a trio of regulatory decision from the FDA and a group of 5 different articles spotlighting data from phase 2 or phase 3 trials.
The first portion of FDA news included in our month in review for September 2023 cardiology on the in review pertains to an FDA Cardiovascular and Renal Drugs Advisory Committee (CRDAC) meeting occurring on September 13, 2023, discussing the application for patisiran in the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM). Scheduled less than a month before the October 8, 2023 PDUFA date, the committee’s vote, which is not binding, was 9 to 3 in favor of the benefit-risk profile of patisiran within the APOLLO-B trial.
On September 22, 2023, Boehringer Ingelheim and Eli Lilly and Company announced the long-awaited FDA approval of empagliflozin (Jardiance) for the management of chronic kidney disease. Approved for reducing the risk of sustained decline in estimated glomerular filtration rate (eGFR), end-stage kidney disease, cardiovascular death, and hospitalization in adults with chronic kidney disease at risk of progression, the announcement comes just more than 18 months after the agent received a historic indication for use in treatment of heart failure regardless of ejection fraction.
The final piece of FDA news in our month in review highlights the FDA’s decision to grant priority review status to the biologics license application for sotatercept, a novel investigational activin signaling inhibitor, for the treatment of adults with pulmonary arterial hypertension. Announced by Merck on September 28, the FDA has set a PDUFA date for the agent of March 26, 2024.
Cardiometabolic Pipeline Updates
On September 7, 2023, Alnylam Pharmaceuticals announced positive topline data from the phase 2 KARDIA-1 trial of zilebesiran in the treatment of hypertension. Announced less than 3 months after phase 1 results were published in the New England Journal of Medicine, results of the phase 2 dose-finding trial suggest use of zilebesiran as a monotherapy could provide significant and meaningful reductions in systolic blood pressure for people with mild-to-moderate hypertension.
New data from the European Respiratory Society International Congress 2023 offered further insight into the potential of sotatercept as a treatment for pulmonary arterial hypertension. Among the 9 total PAH-related, Merck-sponsored abstracts from ERS Congress 2023 were an exploratory posthoc analysis of the STELLAR trial examining impact of sotatercept on cardiovascular function and an interim analysis of data from the SOTERIA open-label extension study, which is billed as the longest safety and efficacy analysis of sotatercept to date.
Results of a phase 2 trial examining use of lorundrostat, an aldosterone synthase inhibitor being developed by Mineralys Therapeutics, suggest the agent could reduce aldosterone synthesis and lower blood pressure in people with uncontrolled or resistant hypertension. A randomized, placebo-controlled, dose-ranging trial named Target-HTN, results of the study suggest treatment with lorundrostat at doses of 50mg and 100 mg once daily led to a statistically and clinically significant reduction of systolic blood pressure, with this effect most apparent in people with hypertension and concomitant obesity.
On September 18, 2023, Anthos Therapeutics announced the discontinuation of their phase 2 AZALEA-TIMI 71 trial due to an “overwhelming reduction” in the study’s composite endpoint of major and clinically relevant non-major bleeding events among patients receiving abelacimab. The decision to discontinue the trial comes after a recommendation from the trial’s Data Monitoring Committee concluding abelacimab contributed to a significant reduction in the composite endpoint, which would make abelacimab the first and only factor XI inhibitor to demonstrate a reduction in major bleeding relative to a direct oral anticoagulant.
On September 27, 2023, results of the NODE-302 study were published in the Journal of the American Heart Association. An open-label extension trial including patients from the phase 3 NODE-301 trial named the NODE-302 study, results suggest users had a 60.2% probability of conversion within 30 minutes of administration, with a median time to conversion of less than 16 minutes.