Lessons Learned Navigating First-In-Human Trial For Pediatric, LMIC Patients

A conversation with Seth Bogner, chairman and CEO of HeartPoint Global

Hanging there on the office wall of an interventional cardiologist was a ubiquitous but also curious item: a cardiac guidewire. It caught the eye of Seth Bogner, now the chairman and CEO of HeartPoint Global.

The guidewire, said the doctor, had been used for surgery over 200 times in Myanmar. Typically, guidewires are single use.

The fact that this particular guidewire had been used 200 times astounded the cardiologist to the point where he felt compelled to commemorate it. For Bogner, the display highlighted a severe scarcity of resources and expertise in much of the developing world. This encounter left a profound impact on Bogner, fueling his determination to bring user-friendly medical technology to regions of the world where people often lack the means or access to surgeries that we often take for granted in affluent nations.

Bringing life-saving therapies to patients in low- and middle-income countries (LMICs) comes with its own unique set of challenges (regulatory compliance and diverse patient enrollment being two of them). But Bogner and HeartPoint Global added another layer of challenge to their endeavor with the inclusion of a pediatric population in attempt to gain approval of INTELLISTENT, a non-surgical structural heart system that addresses a variety of life-threatening cardiovascular diseases, including congenital heart disease (CHD) in children. INTELLISTENT allows for the adjustment of blood flow and pressure during and after placement in the main pulmonary artery and its branches to restore the structure of the heart-lung system.

In this Q&A, Bogner discusses HeartPoint Global’s first-in-human clinical trials and the challenges and opportunities that come with it.

Clinical Leader: HeartPoint Global is approaching its first-in-human clinical trials. What is the unmet market need for the device that HeartPoint Global is developing?

Seth Bogner: Birth defects are common, but there is a paucity of data on the birth prevalence of birth defects in low- and middle-income countries (LMICs) and systematic underestimation.¹ However, globally, the Global Burden of Disease Study by WHO cites 217,000 deaths from CHD, 150,000 of which were infants. It is the most common birth defect in the world. One in 120 babies are born with CHD, and one in four need intervention in the first year of life to survive. Yet only one in 10 have access to quality lifesaving care. These patients are, in many cases, candidates for intervention by INTELLISTENT, the only adjustable device that can treat pulmonary hypertension caused by congenital heart disease (PAH-CHD).

After we are cleared for our initial indication of PAH-CHD, we will be focused on treating left ventricle dilated cardiomyopathy with INTELLISTENT. While there are very expensive and often risky open-chest surgical solutions, including LV assist devices (LVADs) in the developed world, these devices are extremely expensive and, in most cases, do not provide long term viability to patients. According to a recent Journal of the American Journal of Cardiology study¹, patients implanted with LVADs have had poor results using FDA approved devices. 41% of patients had infection, 33 % had major bleeding, 13% had a stroke, and, most disturbingly, 72% have been re-hospitalized. It is estimated that the cost in the U.S. for a patient receiving an LVAD is $1 million per survival year. Heart transplants are another treatment option for LV-DCM but are rarely available in the developing world as there is a chronic shortage of healthy hearts available for transplantation, with patient waiting times ranging from several month to several years before a matching doner heart becomes available². Needless to say, we will have many more and larger clinical trials as we move into left heart issues in the future.

Thus far, what have been some of the wins and some of the challenges regarding INTELLSTENT?

In December, the HeartPoint Global team performed the latest preclinical intervention in Israel with breakthrough results to prepare for in-human trials. INTELLISTENT is minimally invasive, fully reversible, and works well with other therapies, significantly reducing recovery times and potential complications during and after procedures. Because it is minimally invasive, it can be employed to improve or save lives from cardiovascular disease. The trials demonstrated a 100% success rate in the delivery of both the first and second stent. Furthermore, a nine-month study indicated that INTELLISTENT maintained reduced pressure and flow, achieved perfect endothelization, and showed no signs of thrombosis.

With high mortality rates for this age demographic worldwide, pediatric device development is often limited due to high regulatory hurdles and limited financial incentives. Smaller sample sizes and population heterogeneity challenge the ability to obtain sufficient safety data for regulatory submissions. There are also ethical considerations such as making testing safe for children. In addition to these hurdles in the development of medtech devices for pediatrics, the lack of funding puts an even higher barrier on how to bring much-needed medical devices to market for children. Some studies show that advances in devices for children are at least 10 years behind devices for adults, and a lot of therapeutics and devices coming to market cannot be afforded by those in low- to middle-income countries. Only about one quarter of medical devices designed, reviewed, and approved are for children. While the FDA defines children as up to age 21, most of the devices designed “for children” are for those aged 18-21.³

Our CRO partner played a significant role in accelerating our clinical and regulatory strategy in an effort to obtain FDA approval for using INTELLISTENT among pediatric patients. The FDA actually favors pediatric devices and therapies. This includes the Humanitarian Use Device (HUD)/Humanitarian Device Exemption (HDE) pathway. Since 2008, the year Congress began requiring annual Pediatric Medical Device Reports, 29 devices have been approved through the HUD/HDE pathway. Seven of those have a pediatric indication, and four are indicated only in pediatric populations.⁴ We can also get the product to work quicker and then expand on its other capabilities. In our case, we are particularly fortunate because our tech use trajectory has many other uses for other parts of the body, in addition to the heart.

What has been your clinical trial recruitment strategy? How do you educate and support parents and caregivers with children in a trial?

Ethics, compliance, and transparency are our top priorities, and we have been collaborating with hospitals and specific physicians to gain their support and expertise in identifying eligible participants. This involves actively engaging with healthcare institutions and medical professionals with specific expertise in this area and working closely with healthcare providers to identify juveniles that meet the criteria for these trials and transparency with families and caregivers. Clear communication of what exactly the trial will involve has been paramount, as well as gaining a clear understanding, with compassion and curiosity, of the medical challenges that each participant faces.

How do you achieve patient diversity knowing this device is to be used in LMICs upon commercialization?

Accounting for diversity in HeartPoint Global’s trials is imperative to ensure the safety, effectiveness, and applicability of INTELLISTENT across well represented demographic populations. We are ensuring that efforts are being made to include diverse participants regarding gender, race, and ethnicity. One of the reasons why pediatric trials don’t get done in the U.S. is legal liability. This can comprise concerns about informed consent, the potential harm or adverse events that may occur to child participants, and the possible legal responsibilities of the researchers, institutions, and sponsors involved during the trial.  We will be doing cases for our trials both in the U.S. and some of the initial markets where we will seek approval and reimbursement from the payers, which in most cases are national healthcare systems. Our informed consent process is culturally sensitive to meet the legal, ethical, and societal norms of the country in which we will conduct our trial, including translating consent documents into the local language and ensuring they are written in a reading level appropriate for the target participants.

What challenges have you had when recruiting a pediatric population and in planning for later phases?

Pediatric trials are inherently challenging because of the specialized nature of the juvenile population. This includes ethical considerations and obtaining informed consent from parents and legal guardians.

The initial trial phase will be a small group of patients. Depending on feedback from the FDA, it’s likely that our pivotal trial will be considerably smaller than a standard pivotal trial of this kind, given our focus on pediatrics and the fact we are focusing on an unmet need. Despite the inherent challenges in conducting trials involving children and adolescents, the fact that we are working toward such a crucial and impactful cause is proving to be a driving force in our favor.

We are building confidence through a step-by-step approach, starting with adolescents and adults with congenital heart disease (CHD) to first prove safety and efficacy. This will give patients, their families, and healthcare providers more confidence to move forward on pediatric trials. We will then proceed with children ages 5 and above while simultaneously putting a solution for newborns in place.

Overseas, in each country, we are doing more than just trials but trying to move toward commercialization and reimbursement ability. This is a comprehensive approach that involves not just testing a product, but also navigating the steps necessary to make this device accessible and financially sustainable to children and their families in countries where this medical technology is most needed.

References:

1. Varshney A, DeFilippis E, Cowger J, et al. Trends and Outcomes of Left Ventricular Assist Device Therapy. J Am Coll Cardiol. 2022 Mar, 79 (11) 1092–1107. https://doi.org/10.1016/j.jacc.2022.01.017
2. Heart transplant - Waiting list - NHS (www.nhs.uk)
3. Pediatric Medical Device Development and Regulation: Current State, Barriers, and Opportunities, Pediatrics, April 15, 2022 Pediatric Medical Device Development and Regulation: Current State, Barriers, and Opportunities | Pediatrics | American Academy of Pediatrics (aap.org)
4. Pediatric Medical Device Overview (fda.gov)

About The Expert:

Seth Bogner currently serves as chairman and CEO of HeartPoint Global Inc., where he merges his leadership abilities with his long-time goal of creating a business that is both profitable and socially responsible. At HeartPoint Global, he and his team provide global, breakthrough medical solutions for cutting-edge cardiac care that are affordable, safe, and minimally invasive. Bogner founded Union Square Partners Limited Advisory Firm that served institutions and hedge funds and began his career at Loeb Partners Realty, where he played a key role in securing many multi-million-dollar financing deals.

Bogner has more than three decades of experience in principal investing, structured finance, restructurings, and merchant banking, and has also served as the CEO and president of many funded and/or financed entities. To date, he has closed over 200 investments as well as merger and acquisition transactions during his career.