Regeneron Trials Balance Quest For "Scientific Truth" With Patient Impact
A conversation with Andres Sirulnik, MD, Ph.D., senior vice president, hematology clinical development unit head, Regeneron

There is no doubt that the patient perspective is transforming how clinical trials are designed and conducted. We see it everywhere in the way sponsor companies are making inroads to incorporating patient experience in trial designs.
For Regeneron, their intention is a bit broader, moving beyond the traditional focus on “patients” to a people-centric approach that considers the needs of individuals, families, and society as a whole. What’s more, that intention is balanced with company motives to be highly scientific, answering questions and getting answers that reflect “scientific truths.”
In this Q&A, Regeneron’s Andres Sirulnik, MD, Ph.D., discusses these distinct but inextricably intertwined goals in the context of real-world examples from the company’s hematology research.
The patient voice is essential to clinical trial success. When should sponsor companies solicit patients for their input?
We have a people-centric approach. I think “patient” is very limited. “People” indicates more than just a sick individual but a member of society. And that is very important because when you are developing a clinical trial, you need to consider the impact beyond an individual patient.
Regeneron is a science-driven company. Science is at the core of everything that we do. We are asking relevant, meaningful questions that aim to transform the lives of patients. You can do science for the sake of science, you can have all the bells and whistles in a clinical trial, but at the end of the day, you need to ask questions that are relevant to the patient, caregiver and society. That is where our true north is.
So, we first solicit feedback in the very early stages of development. For example, we are investigating a new therapeutic approach in the treatment of hemophilia B. We spent a year and a half before entering the clinic meeting with advocacy groups and patients. And why is that important? Because it's a way to put things into perspective. We sometimes want to answer every question, and we need to step back a little bit and ensure we have a clear picture of the realities the community faces, which can then be infused into our clinical development programs.
Understanding the patient journey is always important. We have scientists at the bench testing cell lines and experimental models. Once they have scientific proof of concept, we have something ready for humans. And that's when you start thinking about how you are going to test that hypothesis. And that's when you start the conversation with patients to better understand the journey of those patients. We try to understand whether patients care about what we could offer.
Who is involved in collecting and implementing that patient feedback?
It is a big team effort. We have patient advocacy teams that help us reach out to patient advocacy groups. We have a medical affairs team that reaches out to treating physicians. And then we have the in-house teams doing the science and considering whether to bring this into the clinic. And we have patient advisory boards. I attend some of these meetings because I want to hear what is most important to patients. And if you don't do these early on, you may be thinking of the most incredible scientific experiment, but its outcomes aren’t important to the patient.
Can you recall a time when you or an entire team had an “aha” moment when talking with patients?
In hemophilia B, we learned the research community was missing a big, important focus – addressing the younger hemophiliac population of adolescents and children. The standard of care currently requires frequent, ongoing medical treatment, which can be difficult on patients and families. But they didn’t care about themselves at age 40, they were concerned about the youth and how early the burden of this disease starts. That moment was the revelation that we really need to focus on the genetic drivers of the condition and advancing research that we can bring to kids with this disease earlier in life.
What things are making it difficult or more complicated for participants to enroll in hematology trials? Are the challenges the same as other therapeutic areas?
Some general aspects are common across the board: access to the clinical trial centers where the trials are being conducted. For example, we are conducting a trial in hypertension in which we’ve collaborated with a company in the U.K. to open temporary clinics in easy to access areas. By going to the community, we make it more accessible to patients and decrease the burden. This gives opportunity to patients who normally would not participate in those trials.
When we go to hematology, blood malignancies, and blood disorders, these studies are more cumbersome and complicated due to the nature of the diseases. Patients and caregivers are often delicately balancing a weakened immune system, organ damage, and other complications from both the underlying disease and prior medicines they’ve been exposed to. Providing access is important, but so is a thoughtful trial design where you balance the pursuit of scientific truth and the experience of patients who are sick and going through a lot. We're trying to be nimble, pare down the bells and whistles sometimes, and focus on that balance between the science and benefiting the patient. When you do that, more patients are willing to participate and, potentially, more people may benefit.
How do you navigate the push and pull between teams where maybe the scientifically minded say, we really want these endpoints and this data, and then patient recruitment tries to rein in expectations to accommodate patients?
It's a constant battle, as you can imagine, particularly for a company that is so laser-focused on science. It is always a discussion. Yes, it would be great to have another cohort of patients at another dose level. Yes, it would be great to do a biopsy. But can we do a different kind of test to learn without imposing on patients?
For example, we are very focused on our multiple myeloma clinical trials using endpoints based on a blood draw rather than a bone marrow biopsy. The FDA has recently accepted a biomarker-based blood test as a surrogate endpoint. So, we can now measure circulating tumor cells via a liquid biopsy rather than taking tissue from patients. We are keenly aware of and focused on decreasing the burden on patients and getting scientific truths that don't require invasive testing.
Specific to hematological conditions, do patients need to be accommodated differently than in other conditions?
In many of these diseases, patients have fatigue and to help them, we offer to provide transportation to the study location. In patients with hematological conditions, we often think about minimizing blood draws, so we don't make patients more anemic. Anemic patients often suffer from weakness. Can they get to their appointment? Should we send nurses? And we do. Even paying for taxis or sending a car service helps. We also look at the cost burden on patients. We take all that into consideration when we design a clinical trial.
As I said, it's not just about the patient; it's a family, it’s society. We try to decrease the burden because it is only fair when people are participating for the good of others, particularly in clinical trials.
Do you also solicit participant input while they're in a trial or after they've been in a trial to improve the next one?
Very much so. We always look at patient-reported outcomes. More and more, our trials include quality of life markers. In follicular lymphoma, we evaluated the overall improvement not only in the quality of patients’ lives but on their activities of daily living and so forth. And more and more, the regulatory agencies and payers around the world are interested in understanding the impact of treatment. So, it's not just about treatment at all costs. You really need to look at the overall impact on people. In the past, researchers did this only in Phase 3 trials; now, we try to learn the impact of our therapies on patients earlier on.
About The Expert:
L. Andres Sirulnik, MD, Ph.D., joined Regeneron in 2020 and serves as senior vice president, clinical development unit head, hematology, leading strategic program direction and clinical sciences work for our early- and late-stage oncologic hematology and late-stage non-oncology hematology portfolios. Before joining Regeneron, Dr. Sirulnik was chief medical officer at Merus N.V., a clinical-stage immuno-oncology company. Prior to that, he spent a decade at Novartis in various roles of increasing responsibility, ultimately overseeing clinical strategy for their immuno-oncology portfolio. Dr. Sirulnik is a licensed physician, formerly practicing at Dana-Farber Cancer Institute and Brigham and Women’s Hospital, and was a fellow in hematology/oncology at Mount Sinai Health System. He completed his medical residency at North Shore Long Island Jewish (LIJ) Health System and conducted post-doctoral work at Columbia University. He received his Ph.D. in medicine and molecular biology from King’s College, University of Cambridge in the U.K. and his M.D. from the University of Buenos Aires, Argentina.