APD418 / Pfizer - LARVOL DELTA

Pfizer Cuts Mid-Stage Candidates Amid Declining Revenues (BioSpace) - "Fresh off its $43 billion acquisition of Seagen, Pfizer is making deep cuts to its Phase II pipeline in cardiology and inflammatory diseases, the company revealed Tuesday during its first-quarter financial report. On Pfizer’s chopping block is temanogrel, an inverse agonist of the serotonin 2A receptor being trialed for microvascular obstruction and Raynaud’s phenomenon related to systemic sclerosis. Pfizer is also dumping its cardio candidate APD418, an antagonist of the beta-3 adrenergic receptor in Phase II studies for acute heart failure...Pfizer’s pipeline clean-out also included the biologic blocker of the TNFSF15 protein for ulcerative colitis and the CXCR2 antagonist RIST4721, which was in Phase II studies for hidradenitis suppurativa and palmoplantar pustulosis."

Pipeline update • Cardiovascular • Heart Failure • Hidradenitis Suppurativa • Immunology • Myocardial Ischemia

A Study to Assess the Hemodynamic Effects, Safety, Tolerability, and Pharmacokinetics of Intravenous APD418 in Adult Participants With Heart Failure With Reduced Ejection Fraction (clinicaltrials.gov) - P2 | N=22 | Terminated | Sponsor: Arena Pharmaceuticals | N=80 ➔ 22 | Trial completion date: Mar 2023 ➔ Sep 2022 | Recruiting ➔ Terminated | Trial primary completion date: Mar 2023 ➔ Sep 2022; Business decision

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Cardiovascular • Congestive Heart Failure • Heart Failure

Intravenous infusion of the beta-3 adrenergic receptor antagonist APD418 improves left ventricular function in dogs with systolic heart failure despite long-term therapy with beta-blockers (HEART FAILURE 2022) - "The current study tested the hypothesis that improvement of LV function with i.v. APD418 is maintained in dogs with systolic HF despite long-term chronic background therapy with the β-blockers carvedilol (CARV) and metoprolol (MET). Acute i.v. infusions of APD418 in systolic HF dogs elicit positive inotropic and lusitropic effects despite long-term background therapy with β-blockers. The findings further support the development of APD418 for the in-hospital treatment of patients with exacerbation of chronic HF."

Cardiovascular • Congestive Heart Failure • Heart Failure

A Study to Assess the Hemodynamic Effects, Safety, Tolerability, and Pharmacokinetics of Intravenous APD418 in Adult Participants With Heart Failure With Reduced Ejection Fraction (clinicaltrials.gov) - P2 | N=80 | Recruiting | Sponsor: Arena Pharmaceuticals | Not yet recruiting ➔ Recruiting | Trial completion date: Dec 2022 ➔ Mar 2023 | Trial primary completion date: Dec 2022 ➔ Mar 2023

Enrollment open • Trial completion date • Trial primary completion date • Cardiovascular • Congestive Heart Failure • Heart Failure

A Study to Assess the Hemodynamic Effects, Safety, Tolerability, and Pharmacokinetics of Intravenous APD418 in Adult Participants With Heart Failure With Reduced Ejection Fraction (clinicaltrials.gov) - P2; N=80; Not yet recruiting; Sponsor: Arena Pharmaceuticals

Clinical • New P2 trial • Cardiovascular • Congestive Heart Failure • Heart Failure

Intravenous Infusion of the β-Adrenergic Receptor Antagonist APD418 Improves Left Ventricular Systolic Function in Dogs with Systolic Heart Failure: β-Adrenergic Receptor Antagonist in Heart Failure. (PubMed, J Card Fail) - "Intravenous infusions of APD418 in dogs with systolic HF elicit significant positive inotropic and lusitropic effects. The findings support the development of APD418 for the in-hospital treatment of patients with acute exacerbation of chronic HF."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure

[VIRTUAL] Selective beta-3 adrenergic receptor blockade increases contractility of human ventricular trabeculae from HFrEF donors (ESC 2020) - "This is, to our knowledge, the first evidence showing that selective blockade of β3-AdrR increases contractility of human ventricular trabeculae from HFrEF donors and suggests that further studies evaluating the therapeutic benefit of APD418 in patients with HFrEF are warranted."

Cardiovascular • Congestive Heart Failure • Heart Failure

"There is one in the works, APD-418." (@SharonAConklin)

"$ARNA is the one that gets me. APD-418, olorinab, etrasimod and ralinepag. 2.4B market cap is ridiculously cheap." (@SharonAConklin)

Intravenous Infusion of the beta-3 Adrenergic Receptor Antagonist APD418 Improves Left Ventricular Systolic and Diastolic Function in Dogs with Heart Failure: A Single Dose, 6 Hours Study (HFSA 2019) - "sThe results of the study indicate that 6 hours intravenous infusions of APD418 in dogs with systolic HF elicit positive inotropic and lusitropic effects. The data support the continued development of APD418 for the treatment of patients with HF."