Damian Pharma

Walchwil, Switzerland, 8 April 2024 – Today, DAMIAN announces online publication of the primary data from clinical study DP13C201 in eClinical Medicine, a Lancet journal. The clinical phase 2 study assessed whether dexfadrostat phosphate, a novel aldosterone synthase inhibitor taken orally once a day for 8 weeks, could provide biochemical and clinical benefit in patients with primary aldosteronism (PA) diagnosed according to the Endocrine Society Clinical Practice Guidelines. The study also evaluated the effect of dexfadrostat phosphate on ambulatory diastolic blood pressure, office systolic and diastolic blood pressure, serum potassium and urinary aldosterone content as well as cortisol levels.

Results from the phase 2 study showed that dexfadrostat phosphate reduced both the aldosterone-to-renin ratio (ARR) and ambulatory systolic blood pressure (aSBP) in patients with primary aldosteronism (PA). Patients in the study who received dexfadrostat phosphate achieved a statistically significant 92% reduction in ARR and normalization of blood pressure (-11 mmHg) in aSBP. Dexfadrostat phosphate also reduced both ambulatory diastolic and office systolic and diastolic blood pressure. Urinary aldosterone was significantly decreased (>90%) while potassium levels were normalized with no impact on cortisol production.

Mulatero et al., eClin Med. 2024; 10.1016/j.eclinm.2024.102576

About the Study
DP13C201 Trial Summary for PatientsDP13C201 Clinical Study Protocol

Disclaimer
Dexfadrostat phosphate is not approved for use in any country.

The final three steps of the biosynthetic pathway of aldosterone are catalyzed by CYP11B2, also known as aldosterone synthase. Hence, inhibiting aldosterone synthase is a targeted mechanism for new therapeutic compounds aimed at reducing aldosterone production. In a new publication by Pignatti et al. the authors reveal that the novel aldosterone synthase inhibitor, dexfadrostat phosphate, aligns with the catalytic moiety of CYP11B2 but not CYP11B1, a related enzyme in the biosynthetic pathway of cortisol. Additionally, both in vitro and clinically, dexfadrostat phosphate demonstrated significant inhibition of CYP11B2 vs. CYP11B1 and did not change basal cortisol levels. Importantly, dexfadrostat phosphate inhibits the final steps in aldosterone biosynthesis, leading to dose-dependent reductions in aldosterone in healthy volunteers.

Pignatti et al., Journal of Steroid Biochemistry and Molecular Biology. 2023; 235.

Doi: 10.1016/j.jsbmb.2023.10640. Online ahead of print.

Today DAMIAN announces the publication of study DP13C101, a phase 1 study evaluating the efficacy and safety of dexfadrostat phosphate in healthy volunteers in the British Journal of Clinical Pharmacology.

Dexfadrostat phosphate is a novel aldosterone synthase inhibitor (ASI), which acts to directly control the production of aldosterone at its origin. “By inhibiting the 3 enzymatic conversions mediated by aldosterone synthase, dexfadrostat phosphate was shown to demonstrate a dose-dependent reduction of the aldosterone-to-renin ratio (ARR, a marker of sodium retention) without affecting the adrenal stress response or the hypothalamic-pituitary-gonadal axis.”

DAMIAN announced in October 2022 the successful completion of a phase 2 study evaluating dexfadrostat phosphate in patients with primary aldosteronism. The study met both its primary endpoints (ARR, ambulatory systolic blood pressure reduction) with high statistical significance following 8 weeks of once-daily treatment. The study also demonstrated a good safety and tolerability profile.

Mulatero et al., Brit J Clinical Pharmacol. 2023 Mar 13; doi: 10.1111/bcp.15713. Online ahead of print

Innosuisse awards third Swiss research grant to DAMIAN to support the further development of its new research project DP20. The new funding supports a collaboration between DAMIAN and its three research partners: Fachhochschule Nordwest Schweiz, ETH Zurich and the University of Bern.

DAMIAN announces new data from the Phase II trial in patients with primary aldosteronism (PA), that showed the investigational compound dexfadrostat phosphate effectively reduced both aldosterone-to-renin ratio (ARR) and ambulatory systolic blood pressure (aSBP). The trial met both primary endpoints with high significance.  

https://dampha.s3.us-east-2.amazonaws.com/assets/uploads/damian-press-release-phase-2-data.pdf

DAMIAN completed the first Phase II study of an aldosterone synthase inhibitor in patients with primary aldosteronism using its novel compound, dexfadrostat phosphate (DP13), in May 2022.  

The Lausanne-based Foundation for Therapeutic Research awards a grant for the development of new therapeutic principles in cardiovascular disease to the University of Torino to investigate dexfadrostat phosphate (DP13). The grant supports the Phase I clinical trial of dexfadrostat phosphate, the first-in-class aldosterone synthase inhibitor from DAMIAN.

DAMIAN executes its Phase I proof-of-concept, double-blind, safety and tolerability study of dexfadrostat phosphate in healthy volunteers (NCT03046589). The Phase I study successfully completed in September 2018.

DAMIAN enrolls the first patients in its multinational Phase II study of dexfadrostat phosphate in patients with Primary Aldosteronism (NCT04007406; EUDRACT# 2019-000919-85).

Innosuisse awards second Swiss research grant to DAMIAN to support the further development of its diagnostic tool, DP14. The new funding follows the successful completion of the design phase and allows the team to execute the in vivo proof-of-concept experiments.

This study by Hundemer et al. evaluated the electronic health records of PA patients on mineralocorticoid receptor antagonist (MRA) therapy and matched hypertensives to investigate the risk of cardiovascular events. The study demonstrated that in PA patients, the risks were higher than in patients with essential hypertension, independent of blood pressure control. The authors speculate that this may have to do, in part, with patients not responding adequately to MRA therapy.

Hundemer et al., Lancet Diabetes Endocrinol. 2018 Jan;6(1):51-59; doi: 10.1016/S2213-8587(17)30367-4

This review article highlights the disconnect between prospective, selective PA studies, which show a relatively high incidence rate, and real-world clinical data which demonstrate that PA remains under diagnosed and under treated. Diagnosis and referral rates remain low, despite the long-term risks associated with uncontrolled PA.

Buffolo et al., Horm Metab Res. 2017;49:908-914; doi: 10.1055/s-0043-119755

The Endocrine Society published an update to their clinical practice guidelines for management of patients with Primary Aldosteronism. These guidelines, based on data from systematic reviews and primary studies, provide an update to the recommendations of whom should be screened and the diagnostic pathway.

J Clin Endocrinol Metab, May 2016, 101(5):1889 –1916; doi: 10.1210/jc.2015-4061