Combination of filgrastim and dutogliptin appears safe in STEMI

The combination of dutogliptin and filgrastim was well tolerated in patients with a recent ST-segment elevation myocardial infarction (STEMI) in a phase 2 trial. Although there were no signifcant differences in efficacy endpoints, favourable trends may support a pivotal phase 3 trial.

“While the event of primary percutaneous coronary intervention (PCI) has drastically improved survival rates in patients with acute myocardial infarction, a significant percentage of patients still develops heart failure, leading to adverse long-term clinical outcomes,” explained Prof. Markus Wallner (Medical University of Graz, Austria) [1]. One approach to tackle this issue is to enhance endogenous repair mechanisms. The current phase 2 trial (NCT03486080) assessed the safety and efficacy of filgrastim, a granulocyte colony-stimulating factor (G-CSF), and dutogliptin, which inhibits the DPP-IV enzyme [2]. Enrolled were 48 participants who experienced STEMI, had a left ventricular ejection fraction of ≤45%, and successfully underwent PCI. They were randomised to placebo or the combination of filgrastim and dutogliptin. As primary outcome measure, safety and efficacy outcomes were reported after 90 days of treatment.

No deaths or treatment withdrawals due to adverse events were reported in the active arm. In addition, no difference was seen in relevant clinical safety endpoints (i.e. non-fatal myocardial infacrtion, stroke, cardiovascular and non-cardiovascular death, stent thrombosis, and heart failure hospitalisation) between placebo receivers and participants who received active treatment. Also, ECG findings, blood tests, and vital signs displayed no differences between participants in the active arm and the placebo arm. Importantly, no serious adverse events were related to active treatment.

Furthermore, participants who received active treatment tended to show benefits concerning some of the efficacy endpoints (i.e. right ventricular ejection fraction, full-width at half maximum [FWHM] late gadolinium enhancement [LGE] mass).

“The study closed early due to the pandemic and we were not able to enrol the originally planned 110 patients,” added Prof. Wallner. “Therefore, the study was underpowered to measure the efficacy of this combination therapy. Nonetheless, a large global outcome trial has been scheduled to start in late 2022.”

1. Von Lewinski D, et al. REC-DUT-002: A regenerative pharmacological approach shortly after STEMI is feasible and promising. LBT Pharmacotherapy, Heart Failure 2022, 21–24 May, Madrid, Spain.
2. Von Lewinski D, et al. 2020;21(1):744.

 

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Posted on 28 July 202213 June 2024