Breakthrough Clinical Results
4TEEN4 Pharmaceuticals announced the publication of data in the European Journal of Heart Failure demonstrating the efficacy and safety of procizumab, a first-in-class anti-DPP3 antibody, in three terminally ill cardiogenic shock patients. All three patients experienced shock reversal within 48 hours after receiving a single dose of procizumab. The drug works by neutralizing circulating dipeptidyl peptidase 3 (cDPP3), a key driver of cardiogenic shock. These positive results support the initiation of a Phase 2a clinical trial (PROCARD) in mid-2025, paving the way for a potential transformative treatment for this life-threatening condition with over 50% mortality.
Key Highlights
- Successful reversal of cardiogenic shock within 48 hours in three terminally ill patients using procizumab.
- Procizumab demonstrated a safe and effective mechanism of action by neutralizing cDPP3.
- Positive results support the initiation of a Phase 2a clinical trial (PROCARD) in mid-2025.
- Procizumab offers a potential transformative treatment for cardiogenic shock, a condition with high mortality.
Incidence and Prevalence
Global Epidemiology of Cardiogenic Shock
Incidence and Prevalence
Current epidemiological data on cardiogenic shock shows limited global comprehensive estimates across all populations and regions. However, several regional studies provide important insights into its occurrence and impact.
Cardiogenic shock complicates approximately 5-10% of acute coronary syndrome (ACS) cases according to 2020 data. In a large Chinese study from the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome registry, 1.1% of 76,807 patients developed in-hospital cardiogenic shock. In an external validation cohort, the rate was slightly higher at 1.8% of 2,205 patients.
A Danish nationwide study spanning 2005-2017 found that among 101,834 AMI patients, 7,040 (7%) developed AMI-related cardiogenic shock (AMICS). The annual incidence proportion of AMICS showed a slight decrease over time, from 7.0% in 2005 to 6.1% in 2017 (P for trend <.0001).
In an Asian STEMI population study, cardiogenic shock developed in 208 out of 1,791 patients (11.6%). These patients were older (61.1±12.5 vs 57.8±12.2 years, P<0.001) and predominantly male (87.0%).
Mortality and Outcomes
Cardiogenic shock continues to have high mortality rates despite advances in care. According to a 2015 publication, mortality from cardiogenic shock exceeds 50%. A 2020 Japanese study identified cardiogenic shock as the leading cause of death in patients with acute myocardial infarction.
In the Danish study, thirty-day mortality for AMICS patients was 60% (95% CI: 59-61) compared to just 8% (95% CI: 7.8-8.2) for AMI-only patients, representing a mortality rate ratio of 11.4 (95% CI: 10.9-11.8). Encouragingly, mortality decreased over time from 68% in 2005 to 57% in 2017 (P for temporal change in adjusted analysis <.0001).
The Asian STEMI study reported significantly higher rates in the cardiogenic shock group for: - All-cause mortality: 59.9% vs 4.7% (P<0.001) - Cardiac mortality: 43.8% vs 2.2% (P<0.001) - Major adverse cardiovascular events (MACE): 59.1% vs 14.0% (P<0.001)
Regional Variations and Risk Factors
The Japanese Circulation Society Cardiovascular Shock registry analyzed 495 ACS patients with cardiogenic shock between 2012 and 2014. This study identified severe hypotension, older age, deep coma, congestive heart failure, and left main trunk disease as independent unfavorable factors in ACS complicated by cardiogenic shock in Japan.
A 2025 study analyzing COVID-19 patients from 32 countries found cardiovascular complications in 13.3% of hospitalized patients, with regional variations. The incidence was highest in the Americas (18.4%) and Europe (14.9%). In this global study, the median age was 59 years (IQR 47-69), and 60.9% were male.
Another 2025 study in Southeastern Virginia found heart failure and shock were the most prevalent cardiovascular conditions (47.2% of discharges) among African American and Hispanic populations. This study revealed female patients incurred significantly higher charges than males across conditions (7.1% higher in heart failure, p<0.0001).
During the COVID-19 pandemic, a 2020 US study using the National Inpatient Sample found COVID-19 was associated with higher rates of cardiogenic shock (aOR:1.36, 95% CI: 1.10-1.68, p=0.004) in AMI patients.
Emerging Mechanism of Action
Emerging Mechanisms of Action for Cardiogenic Shock Management
Pathophysiological Mechanisms and Interventions
Cardiogenic shock (CS) is a life-threatening condition that can occur after myocardial infarction and requires prompt intervention. Recent research has identified several key mechanisms and therapeutic approaches for managing this condition.
Inflammatory Pathways
The inflammatory response plays a significant role in cardiogenic shock pathophysiology:
- The 20-HETE axis is implicated in various vascular pathologies including septic shock, myocardial infarction, and cardiometabolic diseases
- Pharmacological targeting of the 20-HETE-GPR75 axis may provide benefits to patients suffering from cardiovascular pathologies
- 20-HETE receptor blockers represent a promising new class of compounds for intervention
Anti-Inflammatory Pharmacological Interventions
Several anti-inflammatory agents have shown promise in recent studies:
- Colchicine reduced the risk of recurrent MI (RR 0.28, 95% CI 0.10-0.74) in STEMI patients
- Anakinra was associated with reduced risk of new-onset or worsening heart failure (RR 0.32, 95% CI 0.13-0.77) and decreased C-reactive protein levels in STEMI patients
- Amantadine (NMDA receptor antagonism) was associated with a 13% reduction in 3-point major adverse cardiovascular and cerebrovascular events, as well as significantly lower risk of all-cause mortality, AMI, and cerebral infarction
Morphine Postconditioning Mechanism
Morphine postconditioning (MP) has emerged as a potential therapeutic approach:
- MP significantly reduces I/R-induced infarct size, apoptosis, and the release of cardiac troponin I, lactate dehydrogenase (LDH), and creatine kinase-MB
- Heat shock protein 90 (HSP90) is critical for MP-mediated cardioprotection by promoting the phosphorylation of Akt and inhibiting the activation of complement component 5a (C5a) and nuclear factor κB (NF-κB) signaling
- MP increases expression of HSP90 and p-Akt, and decreases expression of C5a, NF-κB, tumor necrosis factor α, interleukin-1β, and intercellular cell adhesion molecule 1
- The C5a/NF-κB signaling pathway is involved in MP-induced cardioprotection
Mechanical Circulatory Support Innovations
Mechanical circulatory support (MCS) systems have emerged as critical interventions for managing cardiogenic shock:
Extracorporeal Support Systems
- Extracorporeal membrane oxygenation (ECMO) as a veno-venous pump-driven system is increasingly recognized as a life-saving procedure in severe respiratory failure
- Extracorporeal life support (ECLS) as a pump-driven veno-arterial cardiovascular support system is increasingly being used in cardiogenic shock after myocardial infarction
- ECLS can serve as bridging to transplantation or as part of extended cardiopulmonary resuscitation
- Pumpless extracorporeal lung assist (pECLA) as an arterio-venous pumpless system ensures sufficient decarboxylation but not oxygenation
Advanced Mechanical Support Devices
- Intracardiac microaxial pump systems (Impella) are being used increasingly as non-permanent MCS
- The HeartMate 3 (HM3) left ventricular assist device (LVAD) can be used as a bridge to heart transplantation (HTx) in cases of STEMI-CS
- POLVAD-MEV paracorporeal pulsatile pumps present a safe option for long-term circulatory support in selected patients
- Percutaneous mechanical circulatory support (MCS) devices can guarantee end-organ perfusion during arrhythmic storms
Hybrid Approaches
- Combined transcatheter aortic valve replacement using a self-expanding valve and left ventricular assist device placement can be effective after primary PCI
- Transcatheter edge-to-edge repair (TEER) is associated with reduction in mitral regurgitation and improvement in mortality in cardiogenic shock complicated by significant mitral regurgitation
Despite these advances, several knowledge gaps remain regarding MCS in cardiogenic shock, including optimal patient selection, timing of initiation, appropriate support system selection, and optimal level of support. The European cardiac surgical register ImCarS has been established to evaluate data from daily clinical practice in cardiac surgery, which may help address these knowledge gaps.
Drug used in other indications
Procizumab Clinical Trials Information
Based on the available information, there is no data regarding Procizumab clinical trials for cardiogenic shock or any other indications. The intervention models, dosing protocols, administration regimens, and phase status of any potential Procizumab trials cannot be determined as no information exists about this drug in the provided context.