clinicaltrialsarena.com
Myocardial infarction (MI), known commonly as a heart attack, is one of the major causes of death globally and can lead to heart failure in a large number of patients.
Current unmet needs of MI include early recognition and treatment, identification of at-risk patients and gender disparities, with more symptoms not recognised in women. According to a report, there will be 74,405,699 diagnosed prevalent cases of MI in 2023 in the 16 countries covered in GlobalData’s epidemiology forecast for MI.
GlobalData is the parent company of the Clinical Trials Arena.
With acute coronary syndromes, prompt medical attention is needed to reduce the amount of damage to the heart muscle. There are very limited treatments currently offering medical intervention at such an early stage which some pipeline medications are trying to address.
In April 2023, the therapeutic pipeline consisted of around 140 pharmaceuticals drugs from discovery through to late-stage clinical development, with 36% of drugs in Phase I and above.
In February 2024, CSL announced that its post-MI drug failed to meet its primary endpoint of reducing the risk of major adverse cardiovascular events in a Phase III trial, showing the difficulties of developing candidates in the space.
Currently, standard of care (SoC) in MI includes medications such as blood thinners or clot-dissolving drugs, coronary angiogram, stenting or in some cases open heart surgery.
Long-term management is also crucial for patients to reduce the risk of repeat occurrence. This may involve lifestyle changes, medication, and regular follow-up care.
In-hospital management of heart attacks has greatly improved over the years, while treatment at the scene has stagnated. Data shows that 50% of heart-attack deaths occur before a patient reaches the hospital.
California-based CeleCor Therapeutics is trying to improve this statistic and is in a pivotal trial of its candidate zalunfiban which is administered in the ambulance.
The Phase III prospective, blinded, randomised, placebo controlled, international study (NCT04825743) is assessing the safety and efficacy of a single subcutaneous injection of zalunfiban in patients with ST-elevation MI (STEMI) in the pre-hospital setting, with the trial due to end in H2 2024.
The trial hopes to enrol 2,499 patients who will be dosed by paramedics. Patients will provide verbal witnessed or short written consent or in extreme cases, the exception from informed consent requirements (EFIC) process of consent will apply.
Zalunfiban is designed to treat STEMI heart attack which account for about 40% of heart attacks. It acts as an integrin alpha IIb beta3 receptor antagonist. Fibrinogen and von Willebrand factors bind to the receptor and cause platelet aggregation, thereby blood coagulation.
Director of the Lindner Center at Christ Hospital in Cincinnati, Ohio, Dr. Timothy Henry says that the agent addresses the unmet need of lack of therapies in the field but questions remain.
“It is a very novel agent and very promising. The advantage is that it has quick onset, and quick down time so you can administer it in the field,” says Henry. “The drug itself, I am very excited about, and it is a needed drug as a subcutaneous antiplatelet drug. With oral antiplatelet drugs, lots of people have nausea and vomiting so a subcutaneous candidate is very attractive. The question however is what is the right trial design?”
Professor of cardiology and imaging and director of research at the University of Glasgow, Professor Colin Berry, adds that the novel small molecule might be used along with other drugs if approved such as Glycoprotein IIb/IIIa Inhibitors.
BioCardia is conducting a Phase III, randomised, controlled, international trial (NCT02438306) evaluating the safety and efficacy of CardiAMP cell therapy. The trial is due to end in December 2024.
Although interim results show that the candidate is unlikely to meet its primary endpoints, the company remains hopeful, saying it is exploring alternative Phase III trial protocol, commenting that the therapy has been successful in some patients, with the roll in open label cohort of 10 patients achieving 100% survival at a two year follow up.
The current trial is using the Finkelstein Schoenfeld (FS) test as the primary endpoint which has multiple criteria including heart death equivalent, non-fatal major adverse cardiac and cerebrovascular events (MACCE) events, and six-minute walk distance (6MWD).
BioCardia says if it conducts a further study with longer treatment times and the 6MWD is replaced with a different endpoint, the company believes it is likely to be a more successful trial.
CardiAMP is an autologous bone marrow cell therapy. The therapy system works by extracting bone marrow from the hip of a heart attack patient, dosing and administering it to heart tissue. The whole process is much quicker than most cell therapies, with the cells being reintroduced to the body after just four to six hours from extraction compared to several days.
Henry says that this is a very interesting trial to watch as it could bring cell therapies into the space while keeping treatment within the timely manner needed in these kinds of medical emergencies.
“It's an important trial to watch because it looks at whether autologous selected bone marrow can improve overall health heart function in ischemic patients with ischemic cardiomyopathy,” says Henry. “It’s a high-risk population and you are choosing patients with better cells. My understanding is that about 75 to 85% of patients will fit the criteria.”
Berry says that there could be limitations with the candidate in terms of administration but hopes that the efficacy will override these concerns.
“There could be issues around re-administration, dosing, cost, logistics which could be limiting factors but if there is good evidence of safety and efficacy, it could be a good candidate,” Berry explains.
Thrombolytic Science International is conducting a Phase II trial of its pipeline candidate HisproUK (TS-01), a plasminogen activator, which is administered shortly after a cardiac arrest to unblock blood vessels in patients.
The open-label, randomised Phase II trial of the candidate (1006643) is investigating safety and efficacy of HisproUK in patients who attend hospital with a heart attack, with an expected delay of at least one hour before being treated at a percutaneous coronary intervention (PCI) capable hospital with a stent.
The company hopes to enrol 48 patients at a single NHS site, the University Hospital of Wales in Cardiff, UK.
HisproUK is a plasminogen activator consisting of a single-site mutant of native pro-urokinase, preceded by the administration of the natural plasma inhibitor, C1 esterase inhibitor. Plasmin degrades fibrin clots, fibrinogen, and other plasma proteins.
A Phase II trial of the candidate in ischemic stroke was unsuccessful, with no difference between the candidate and comparator. Despite this, the company remains hopeful for the candidate in MI.
Berry hopes that the candidate may address the unmet need of limited efficacy in thrombolysis candidates.
“One of the issues with thrombolysis, systemic and intracoronary and indeed cerebral and intra-arterial is limited efficacy,” Berry says. “So, there is an unmet need in relation to the efficacy of thrombolysis, and this compound is novel and certainly merits further investigation.”
Henry comments that the therapy will help with patients who have a delay before treatment which, although not frequent, does occur, even in Europe and the US.
“There's a lot of people around the world that present with delay. Most people are able to do primary PCI but even in the US, a fair number of people experience delays so there is a need for a new novel lytic,” says Henry. “We have done this before, it is not a new theory, but there is some excitement because this is a novel lytic.”