CELEBRATE: Zalunfiban, a Novel Glycoprotein IIb/IIIa Inhibitor, Helps in STEMI

NEW ORLEANS, LA—A single subcutaneous injection of a novel, small-molecule glycoprotein IIb/IIIa inhibitor administered at first medical contact in patients with suspected STEMI improves the patency of infarct-related arteries at cath lab arrival and reduces the likelihood of adverse events at 30 days, according to results from the CELEBRATE study.

Zalunfiban (CeleCor Therapeutics), which is delivered by emergency medical services, represents an effort to reduce the prolonged ischemic time as patients are taken to a PCI-capable hospital, said investigators this week during the American Heart Association 2025 Scientific Sessions.

“Time is muscle, as we all know, and therefore it’s very important to have an open infarct-related vessel upon arrival of the patient in the cath lab as early as possible after the prehospital diagnosis,” said lead investigator Arnoud van ‘t Hof, MD, PhD (University Medical Center Maastricht, the Netherlands).

Christopher Granger, MD (Duke University School of Medicine, Durham, NC), one of the CELEBRATE researchers, said there is a “clear and compelling need” to improve perfusion between first medical contact and the cath lab. “I think it’s one of the more important opportunities that we have in all of acute cardiovascular care,” he told TCTMD.  

CELEBRATE was published simultaneously in NEJM Evidence.

Nearly 2,500 Patients

Randomized trials with oral P2Y12 inhibitors were not successful at improving infarct-related-artery patency, but use of intravenous glycoprotein IIb/IIIa inhibitors has been associated with gains. In the ADMIRAL trial, for example, early treatment with abciximab in patients with acute MI improved patency before PCI and clinical outcomes at 6 months. However, early trials of glycoprotein IIb/IIIa inhibitors were conducted in an era before the development of more-potent P2Y12 inhibitors and low-profile DES.

Additionally, the first-generation glycoprotein IIb/IIIa inhibitors are “difficult to administer,” said van ’t Hof, noting they require continuous infusion and carry a risk of severe bleeding and thrombocytopenia.

Zalunfiban, given as a single subcutaneous dose at first medical contact, blocks the final step of platelet inhibition. It stabilizes the glycoprotein IIb/IIIa receptor in its inactive form, which is believed to reduce the risk of thrombocytopenia. Near-complete platelet inhibition is achieved within 15 minutes, and the half-life is short at roughly 1 hour. Platelet function is returned to normal in approximately 2 hours, which allows patients to undergo CABG surgery, if needed.

CELEBRATE included 2,467 patients (mean age 63 years; 79% male) who presented within 4 hours of the onset of persistent ischemic chest pain and had presumed STEMI on ECG. Patients were randomized 2:1 to zalunfiban or placebo, with 853 patients receiving a 0.11-mg/kg dose of zalunfiban and 818 receiving a 0.13-mg/kg dose.

The median time from symptom onset to receiving the study drug was 90 minutes, and the time from symptom onset to PCI was 140 minutes. Nearly all patients (95%) were treated with aspirin, heparin, and a P2Y12 inhibitor prior to PCI, the vast majority of which was performed via radial access.  

The primary endpoint was a 30-day major adverse event composite evaluated in a hierarchical fashion: all-cause mortality, stroke, recurrent MI, acute stent thrombosis (within 24 hours) following PCI, new-onset heart failure (HF) or HF hospitalizations, and MI defined by an increase in high-sensitivity cardiac troponin T levels 30 times the upper limit of normal (within 24 hours).

Treatment with zalunfiban reduced the risk of the primary endpoint by 21% compared with placebo (OR 0.79; 95% CI 0.65-0.98). When the components were analyzed individually, the benefit was driven by a reduction in risk of acute stent thrombosis within 24 hours and MI defined by the increase cardiac troponin T. There also was a nominal reduction in the HF endpoint. Adverse endpoint-free survival at 30 days was 13.3% with zalunfiban and 9.8% with placebo (P = 0.016).     

Patency of the infarct-related artery prior to angiography was significantly better among the zalunfiban-treated patients as well. In total, 52% of patients in the treatment arm had TIMI grade 2 or 3 flow in the infarct-related artery at the time of angiography versus 45% in the placebo arm (P = 0.002).  

“This was also associated with an improvement in ST-segment resolution shortly before PCI,” said van ’t Hof. “More patients came in with a normalized ECG.”

GUSTO severe or life-threatening bleeding rates were 1.2% and 0.8% in the zalunfiban and placebo arms, respectively (P = 0.40), but there was an increase in mild-or-moderate bleeding with the glycoprotein inhibitor (6.4% vs 2.5% with placebo; OR 2.64; 95% CI 1.61-4.52). There was no difference in risk of intracranial hemorrhage or gastrointestinal bleeding in the treatment arms.

Long Delays in the US

To TCTMD, Granger said that while there have been very successful efforts to improve the quality and timeliness of care for STEMI patients, such as with the AHA’s Mission: Lifeline program, there are still delays, especially among patients who require transfer to a PCI-capable hospital. In one recent analysis, just 17% of patients who required interhospital transfer were treated within 120 minutes.

Zalunfiban, he said, has some nice characteristics and doesn’t substantially increase the most serious types of bleeding. “So, we’re excited,” he said. “It’s potentially another important tool before hospital arrival.”

It’s potentially another important tool before hospital arrival. Christopher Granger

Dharam Kumbhani, MD (UT Southwestern Medical Center, Dallas, TX), who wasn’t involved in the study, believes there is a need for an agent like zalunfiban, “especially if you expect the total ischemic time to be longer.” The subcutaneous administration is an advantage, as is its short half-life.

“It does check a lot of boxes,” he told TCTMD.

One limitation of the study, said Kumbhani, is that the median time from symptom onset to PCI was roughly 2.5 hours. “The total ischemic time was very short,” he said, noting that the interval can be as long as 6 hours in the US. “There may be a role for agents like this in that setting, but we need to test it.”

Elliott Antman, MD (Brigham and Women’s Hospital, Boston, MA), the discussant following CELEBRATE’s presentation, said the investigational glycoprotein inhibitor does appear to have some advantages with its design, but admitted that the “hierarchical endpoint is challenging to interpret.” Also, there was variation in zalunfiban’s effect on components of the composite endpoint, which he said was unexpected based on the study’s design.

Given the higher risk of bleeding, by some definitions, it will be important to see the effects of zalunfiban by dose and in patients treated with femoral access, he added.  

“The bottom line for me is zalunfiban is an innovative drug that allows testing of an extremely important concept, and I strongly feel that it deserves further study,” said Antman.