Heart failure drugs in the pipeline now number more than 100 and include familiar names plus dozens of new ones. Get a top-line look at 6 of the most promising.
Heart failure drugs in the pipeline now number more than 100 and reflect research ongoing at more than 100 pharmaceutical companies.
Spanning developmental stages, they include familiar agents such as omecamtiv mecarbil and investigational molecules, including a β3-adrenergic receptor antagonist and cardiac myotrope.
A report from market research company DelveInsitght, Heart Failure—Pipeline Insight, 2021, provides a comprehensive view of all the investigational agents. The full report must be purchased but we offer concise summaries of 6 novel therapeutic strategies that deserve attention.
HF on the rise. More than 6.5 million Americans age ≥20 years have HF and the prevalence is rising with aging of the population, according to the American Heart Association. The prevalence is higher in women than in men ≥ 80 years, and the overall prevalence is especially high in Black women and men. About half of incident hospitalized HF events are characterized by heart failure with reduced ejection fraction (HFrEF) and half by heart failure with preserved ejection fraction (HFpEF). Circulation.
Leading cause of death. HF accounts for close to 400,000 deaths each year, making HF the leading cause of death in the United States. More than half of patients with HF die within 5 years from the time of diagnosis, pointing to a worse prognosis than a cancer diagnosis. The economic cost of HF in the United States is estimated at >$30 billion.
A drug on the fast track. In January 2020, the FDA granted Fast Track designation for APD418 (Arena Pharmaceuticals), a β3-adrenergic receptor antagonist and cardiac myotrope currently in the Phase II stage of development for decompensated heart failure. APD418 is designed to improve cardiac contractility with minimal effect on heart rate and blood pressure. Arena Pharmaceuticals.
More facilitated development. Omecamtiv mecarbil (Cytokinetics), a novel selective cardiac myosin activator (the first of this class) in development for HFrEF, received the FDA’s Fast Track designation in May 2020. In the Phase III GALACTIC-HF trial, the incidence of a composite of an HF event or death from cardiovascular (CV) causes was lower in patients with HFrEF who received omecamtiv mecarbil than in those who received placebo. New England Journal of Medicine.
Finerenone gains approval. Kerendia (finerenone) (Bayer HealthCare Pharmaceuticals) is a nonsteroidal, selective mineralocorticoid receptor antagonist. In July 2021, based on Phase III FIDELIO-DKD trial results, the FDA approved finerenone to reduce the risk of sustained estimated glomerular filtration rate (eGFR) decline, kidney failure, CV death, non-fatal myocardial infarction, and hospitalization for HF in adult patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D). FDA Approval.
Professional Prescribing Information.
Finerenone investigated for nondiabetic CKD. Following studies that showed the CV benefits of finerenone for patients with CKD and T2D, Bayer is now investigating its efficacy for delaying CKD progression in patients who do not have T2D. In FIND-CKD, a multicenter, randomized, double-blind, placebo-controlled Phase III study, researchers are evaluating the mean rate of change in eGFR slope from baseline to 32 months. Bayer
IONIS-AGT-LRx for HFrEF. IONIS-AGT-LRx (Ionis Pharmaceuticals) is a ligand-conjugated investigational antisense medicine designed to reduce the production of angiotensinogen to decrease blood pressure in patients with treatment resistant hypertension (TRH). The odds of having fatal and nonfatal CV events are increased 3-fold in patients with TRH compared with those with controlled hypertension. IONIS-AGT-LRx is in the Phase II stage of development to treat HFrEF. Ionis Pharmaceuticals.
AZD4831 for HFpEF. AZD4831 (AstraZeneca) is a novel oral myeloperoxidase (MPO) inhibitor for patients with HFpEF currently in the Phase II/III stage of development. MPO-derived oxidants have been shown to contribute to tissue damage, inflammation, and fibrosis. The Phase IIa SATELLITE trial is assessing the target engagement, safety, and tolerability of AZD4831 in patients with HFpEF. The AZD4831 group showed a 69% reduction in MPO activity. AstraZeneca.
JK07 for patients with HFrEF. JK07 (SalubrisBio) is a neuregulin-1 fusion antibody drug that has shown regenerative potential in large and small animal models of HF, including HFrEF and HFpEF. SalubrisBio is currently studying JK07 in a Phase 1 trial (NCT04210375) to evaluate its safety, pharmacokinetics, and activity in patients with HFrEF. SalubrisBio.