Cardiovascular Diseases
Heart failure with preserved ejection fraction (HFpEF) is a distinct form of heart failure with limited options for therapy and an urgent need for new treatment strategies. Paradigm’s cardiovascular work is exploratory and entirely preclinical: injectable pentosan polysulfate sodium has been studied in rats, including the ZSF-1 obese rat model of HFpEF, with the Center for Heart Failure Research at the University of Oslo. No clinical trial of PPS in heart failure has been conducted.
Cardiovascular Development Program
Paradigm’s cardiovascular development program is exploratory and centres on heart failure with preserved ejection fraction (HFpEF). The rationale for injectable pentosan polysulfate sodium (PPS) here rests on ADAMTS-4, an extracellular matrix degrading enzyme present in myocardial tissue, and on the inflammation and vascular endothelial cell activation that accompany adverse cardiac remodelling.
All of the work to date is preclinical and was carried out in rats. PPS has been studied in a pressure-overload model created by aortic banding, published in 2014, and in the ZSF-1 obese rat model of HFpEF, run in collaboration with the Center for Heart Failure Research and the Institute for Experimental Medical Research at the University of Oslo. No clinical trial of PPS in heart failure has been conducted, and there are no human data for PPS in any cardiovascular indication.
HFpEF · Heart failure with preserved ejection fraction
- Status
- Exploratory. Preclinical proof of concept
- Stage
- Preclinical only. No clinical trial of PPS in heart failure has been conducted
- Model
- ZSF-1 obese rat, a standard model of HFpEF
- Collaboration
- Center for Heart Failure Research and the Institute for Experimental Medical Research, University of Oslo
- Target under study
- ADAMTS-4, which degrades the extracellular matrix component versican in myocardial tissue
Status and milestones
Paradigm’s cardiovascular program is focused on the potential application of PPS in heart failure with preserved ejection fraction (HFpEF). Preclinical studies in the ZSF-1 obese rat model have demonstrated signals of improved diastolic function and reduced myocardial tissue remodelling. The program remains preclinical, with no cardiovascular clinical study currently guided, while Paradigm’s clinical development remains focused on knee osteoarthritis.
- Jun 2017 Paradigm entered the heart failure program, in-licensing worldwide rights from the University of Oslo covering inhibition of ADAMTS-4 and ADAMTS-5 in cardiac remodelling and chronic heart failure. Complete
- Oct 2021 Priority established for Paradigm’s HFpEF-specific patent, Treatment of heart failure with preserved ejection fraction, covering the use of PPS in HFpEF. Complete
- Dec 2021 Positive topline results reported from the ZSF-1 obese rat model of HFpEF, demonstrating potential improvements in diastolic function and reduced accumulation of versican cleavage products following PPS treatment. Complete
- Aug 2022 Paradigm reported completion of its HFpEF preclinical study using the ZSF-1 model and commenced consideration of the next stage of development and clinical translation. Complete
- Oct 2022 International PCT patent application for Treatment of heart failure with preserved ejection fraction filed by Paradigm, the University of Oslo and Oslo University Hospital. Complete
- May 2023 International HFpEF patent application WO2023070164A1 published. Complete
Reported figures
The following figures are reported for heart failure, and for HFpEF specifically. They describe the disease. They are not statements about any Paradigm product.
-
Heart failure
59.7%
HF 5-year survival rate: 59.7% (1)
-
Heart failure
20 – 25%
HF hospital re-admission rate: 20 – 25% (11)
-
Heart failure
>50 %
Absolute number of hospital admissions for HF projected to increase by >50 % over the next 25 years (12)
-
HFpEF
32 million
Global prevalence of HFpEF is estimated to be more than 32 million (11)
-
HFpEF
29%
In HFpEF, the rehospitalisation rate was found to be 29% within 60–90 days of hospital discharge (13)
-
HFpEF
1 in 10
Lifetime risk at age 40 for developing HFpEF is 1 in 10 (14).
Where to go from here
If you or someone you care for is living with heart failure, there is no Paradigm heart failure study to join. Paradigm’s cardiovascular work is preclinical and has been carried out in rats; no clinical trial of pentosan polysulfate sodium in heart failure has been conducted. Paradigm is not able to discuss an individual’s eligibility for a clinical trial, or any matter relating to your condition. Your own doctor or cardiologist is the right person to talk to about your care.
For investors and potential partners: heart failure is one of several exploratory indications for PPS, alongside Paradigm’s clinical programme in knee osteoarthritis. Announcements and disclosures are published in full on this hub.
Injectable pentosan polysulfate sodium is an investigational medicine. It is not approved for the treatment of heart failure, or of any other cardiovascular condition, in any jurisdiction; it is not available outside a clinical trial; and no clinical trial of it in heart failure has been conducted. Nothing on this page is medical advice or an offer of treatment.