Meet Loren Peña, MD, PhD, Medical Director, Medpace
Medpace is pleased to announce the addition of a new rare disease and metabolic expert, Dr. Loren Peña, to the medical leadership team.
Dr. Peña is board certified in pediatrics and clinical genetics, with 15 years of clinical experience and a focus on inborn errors of metabolism, lysosomal disorders, skeletal dysplasias, and other rare conditions. She has extensive experience in human subjects protections, most recently as chair of the institutional review board at a children’s hospital. Dr. Peña has over 50 publications in rare and ultra rare disorders and has been a Principal Investigator (PI) or sub-investigator for over a dozen protocols for rare disorders, bringing a unique perspective to the Medpace team.
In this brief interview, we learn more about Dr. Peña’s background and the expertise she brings to Medpace.
Tell us about your background. How does your prior experience translate to your work at Medpace?
Before coming to Medpace, I had an academic clinical practice for 15 years, where I evaluated patients with suspected heritable conditions, sent diagnostic testing, and managed patients after diagnosis. My expertise is in diagnosis and management of skeletal dysplasias, lysosomal storage disorders, and biochemical disorders, some of which were treated with specialized diets or supplements. Part of my academic practice was also in clinical research, and I worked in the rare disease space as a Principal Investigator (PI) for many trials for rare disorders. I was particularly interested in innovative technology, so in addition to enzyme replacement therapy, I have experience with substrate reduction therapy, AAV based gene therapy, and mRNA-based therapy.
Since I was well acquainted with the clinical research space, I decided to explore a clinical research career that put to use my previous experience. I was pleasantly surprised that Medpace was in the Cincinnati area, with a big infrastructure for clinical research. I bring to Medpace clinical experience with rare disorders and therapeutics, and clinical research expertise from the point of view of research ethics and human subjects protections.
What drew you to Medpace? What sets Medpace apart from other global CROs?
I like the broad scope that a CRO can provide; the sandbox is bigger than being in a team that manages only one product. Additionally, I like that Medpace is an international company because my experience has been mainly US-based, so I am intrigued about the regulatory infrastructure in other countries. The most important thing that I observed as I considered Medpace is that the Medpace team is very well integrated. The strong team integration really helps while working with Sponsors and sites to make the process and communication seamless. Sometimes when teams are siloed, there’s inevitably some sort of space that neither team covers, which doesn’t make for a great clinical research experience. Due to this I really like the fact that the teams at Medpace are cross-functional, and that every team member wants to succeed and help whether in their scope of practice, or find the right person that can help.
What motivates you and your interest in clinical research – specifically in rare disease and metabolic?
Clinical research caters to curiosity and inquisitiveness, which is part of my interest in the field of genetics. There are a lot of opportunities for deep thinking while exploring mechanisms of disease, especially in needing to understand what the mechanism of the disease is in order to develop potential therapies. Ultimately, the reason why I’m interested in therapeutics is the opportunity for making a difference in patients’ and families’ lives. There is hope for a cure or a treatment for affected individuals, which are only available in a small fraction of rare disorders.
The other piece that motivates me is that disorders are frequently so rare that there are gray areas. For example, sometimes we don’t have a natural history, we don’t know what the longitudinal history is, and we don’t have treatment guidelines because there isn’t enough experience with the rare disorder. These are all opportunities to develop treatment protocols, test treatment protocols, or start to collect longitudinal data that can be applied to taking care of patients.
What challenges are specific to rare disease clinical development?
There are some very specific challenges in rare diseases, including ascertainment and recruitment. Sometimes there can be delays in diagnosis for patients, which can be very frustrating especially when there’s a treatment for the condition and diagnosis is particularly of importance. Social media has made a big difference for rare disorders. Often there won’t be a particular clinician who is a champion for the condition. This is where parent groups and social media can facilitate for a group of stakeholders to coalesce and share knowledge.
Another obstacle to rare disease clinical development is knowledge of treatment endpoints. It is important for us to understand what the longitudinal history of the disorder might be, or what the full scope of symptoms, findings, and complications can be in a condition as we’re thinking about potential objectives for a clinical investigation. It becomes very difficult to develop a hypothesis or a goal for a therapy if we don’t fully understand the spectrum of symptoms and complications of a disorder.
There are also challenges in rare disease clinical development from the ethics and regulatory point of view. First, how do we set up preclinical experiments to show safety and potential clinical effect when trying to implement recruitment at a very early age? Additionally, how do we operationalize a clinical trial that will justify applying those compounds at a very young age? This can sometimes scare groups away from developing a treatment. However, there is a big opportunity in these early fatal disorders to show a change and a potential benefit for these compounds in terms of survival.
There is a remarkable group that I have admired from afar for a long time, who set the standard, in my mind, that a condition is never too rare to develop a treatment for. The group showed that we can conduct trials in rare disorders like Hutchinson-Gilford progeria syndrome, which is a disorder of premature aging in which teenagers have strokes and heart attacks and die at a young age. In about 20 years, a set of parents organized a community of families and researchers that developed a clinical and research program, leading to identification of a change in the LMNA gene that caused the condition. With that knowledge they funded 3 international clinical trials and at least one of those studies led to FDA approval for a treatment regimen that led to improved survival. They did this by designating one center and facilitating international travel for the participants to that center. This group started off with no gene identified for the condition, found a prevalence of about one in four million, and were able to launch and fully recruit for multiple clinical trials in the span of 20 years, which is truly remarkable given the challenges of rare disease clinical development.
You bring a unique perspective from your experience as a PI. Can you share some key considerations when conducting rare disease clinical trials?
In rare disorders, there is a need for sophisticated systems as methods for delivery become more complicated or invasive. With my experience as a PI, I can identify some of the challenges to implementation and share practical knowledge on addressing the challenges. Many of these studies will require a champion for the trial and for the patients because many times these complicated trials will test systems and hospitals, so it is important to identify providers that are dedicated to bringing these trials as a source of hope for patients. While in clinical practice, I considered that part of my duty on behalf of affected individuals was to “poke” the system and ask leadership to see if the institution could help us make allowances for these very complicated studies. I bring that perspective to this role at Medpace, even though I’m not first in line with patient care. I can brainstorm with a site for operationalizing a study through my experience in clinical care and in clinical research. If there are barriers that are identified in the protocol, I can help think creatively in a way that helps families while also upholding the principles of clinical research and Medpace’s vision. I can help operationalize these studies because I have been in the trenches and have planned how to deploy these studies, so I can speak with the teams about what to consider as we help sites bring the trial to their hospital.
From a clinical development standpoint, what new innovations are you most excited about?
It seems that no disorder is too rare these days, so there is a lot of activity and interest in clinical development. I believe one big innovation coming is genomic editing for rare disorders, which seems well positioned to address disorders affected by non-coding elements. We have focused on diseases caused by one gene, but as we understand in genetics now, there’s an even bigger segment of the genome that doesn’t code for genes that are probably important for gene regulation. We are now entering the era where we have tools to address those non-coding regions.
Additionally, we seem to be making gains in addressing central nervous system (CNS) symptoms with new routes of delivery. We’re delivering therapies in more invasive ways for CNS disorders, and I think the patient community is becoming used to recalibrating their concept of risk and benefit due to hope for an effective treatment. As a community of stakeholders, I think we would do well to recalibrate our concept of risk and benefit because it seems to be evolving for affected individuals and/or their families. It seems that our concept of risk and benefit as an outsider—not being the affected person or a family member—is different from someone who is experiencing this condition and considering receiving invasive treatments. It’s a very interesting place to be.
How do you envision rare disease or metabolic clinical development evolving over the next 10-15 years?
We have moved on from the standard enzyme replacement therapy to other sophisticated systems that are based on the genomic mechanism of disease, such as gene replacement or editing. In the next 15 years, I expect sizable change from the clinical and research perspective. I mention the clinical perspective because a health care provider’s role will be impacted by the progress of clinical research. For example, while some biochemical disorders are currently treated with specialized diets, in 15 years we may have a curative treatment instead. From the research perspective, development of new therapies will continue, but we will also be focusing on the long-term effects of approved therapies, their durability, and how we monitor patients to make sure they continue to derive a benefit from the therapy years later. I think that partnerships with families and support groups will become ever more relevant for clinical development. I mentioned the evolving concept of risk in a previous question, and I think it will become so important to elicit different points of view from various stakeholders during the clinical development of a candidate compound – what is an acceptable risk, and what is a desirable outcome as we develop a pathway to regulatory approval.
I mentioned an exceptionally rare disorder in a previous question, and I want to emphasize that no disorder seems to be too rare for development of a new therapy these days. So, registries and longitudinal history initiatives will become much more relevant for endpoint development, including surrogate endpoints that may help address concerns related to long timelines to approval. Despite the interest and vigor behind rare disease therapeutics, only a fraction of disorders have an approved treatment or treatment in development. Partly reflective of this lack of treatment options, we have two newer initiatives that seem to be in a gray zone from the clinical development perspective: n-of-1 therapies in which a compound is developed for one specific patient, and the right to try movement for those with debilitating disorders. Each one represents a very interesting scenario intersecting research and clinical care, with the promise of hope but also the possibility of big risk due to the lack of safety and efficacy data. All in all, clinical development for rare disorders is in an exciting phase with many thought-provoking possibilities.
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