Designing Clinical Trials with the Patient in Mind

Jenn McNary is a mother of children with rare conditions, as well as an outspoken advocate who has sought to elevate the patient voice in rare disease drug development. She was responsible for the organization of the largest FDA advisory committee hearing in history, with more than 1,000 Duchenne Muscular Dystrophy advocates, families, clinicians, and researchers in attendance. Now, as executive director and head of patient advocacy and engagement for Fulcrum Therapeutics, she’s working to inform company’s clinical trial designs through bringing in patients’ perspectives. We spoke to McNary about her journey as a patient advocate, her role as an advocate within industry, and how her views on the patient voice have evolved.

Daniel Levine: Jenn, thanks for joining us.

Jenn McNary: Thank you for having me, excited to be here.

Daniel Levine: We’re going to talk about your own journey as a patient advocate, the important role of the patient voice and how drug developers can better incorporate the patient voice in their trial designs. I think many listeners may be familiar with your advocacy work, but perhaps we can begin with how you became involved in the world of rare diseases. What happened?

Jenn McNary: So, I became involved as a caregiver actually. I was a young adult and I actually had my first two sons Austin and Max. I was attending a community college course on early childhood development and through that course, I noticed that Austin, who is my oldest son, was not meeting milestones like he should be. As I observed him I was able to get him in, and this is not usual with Duchenne muscular dystrophy, but I got him in with a physical therapist who was able to quickly diagnose and identify Duchenne muscular dystrophy. So, he was diagnosed at that point. He was three years old and I really pushed for my second son Max, who was at that time a newborn. to be tested as well, and he was tested and unfortunately also had Duchenne muscular dystrophy. I now have four biological children and actually two foster children at this time. My youngest son James is 14 now, but he went on to be diagnosed with two different rare diseases at the age of 10, both primary immune deficiency and congenital cholesteatoma. So, the world of rare diseases for me starts at home.

Daniel Levine: Caring for six children, three of whom have a rare disease, I suspect, would keep most people busy, but how did you become involved in the world of advocacy?

Jenn McNary: I knew when my boys were diagnosed that, I asked the question first, was this like cancer? Was there a chemotherapy or something that I could give them to treat the Duchenne? I was quickly told and realized through my own conversations that this disease was fatal and was not in fact treatable. And in fact, the physician at the time told me that, it’s really unfortunate that these two boys have received a diagnosis at such a young age because there was nothing I could do. And so I just needed to take them home and, and love them. and, you know, know that they were not going to outlive childhood, I was raising children that were going to pass away, and I really didn’t want to take that answer. I wanted to first get them the best care possible. So I started as an advocate for my own children, researching specialists and engaging with the Duchenne community through various methods. And my goal was to find my community and was a community that didn’t want to wallow, that didn’t want to obsess about the diagnosis, but wanted to move forward and find the best treatment and the best options that could help them through my advocacy work, just advocating for my own family. I met that network, that broader Duchenne family, and I found a home in an organization called Parent Project Muscular Dystrophy, and I started attending those conferences. Those conferences really motivated me. There were a lot of researchers and doctors that were on the cutting edge of trying to determine what might work for this disease. And, eventually through my contacts at this conference, my son Max nine years later was able to enroll in the first real pivotal clinical trial for Duchenne that resulted in an approval. That quickly catapulted me into the professional advocacy space.

Daniel Levine: You were outspoken as a parent and advocate with the FDA. You had one son in the clinical trial for Sarepta’s DMD therapy, but your older son, Austin was excluded from the trial because he was unable to walk and couldn’t be evaluated on a six minute walk test, one of the endpoints for the study. As you look back at those interactions and the ones that followed with both the FDA and Sarepta, what was your sense of how industry and regulators viewed the patient voice and did you see a need for change?

Jenn McNary: So, very early on, I knew during the evaluation process for this trial, that Max might be eligible, but that Austin clearly wasn’t. He had stopped walking at the age of 10 and a half and my thought process was really okay. You know, Max is the stronger of the two, and if this works we will know it really quickly. And then Austin will get access. And really what I learned is drug development was not set up that way back then. There wasn’t as much room to include patient perspectives, even in the design of the clinical trial. And so it was very focused on endpoints like the six minute walk test that you mentioned where it wasn’t necessarily the most meaningful to us. We went on to really want to look at things like fatigue and a reduction in falls; you know, Max stopped asking to use his wheelchair about five or six months into the study. His manual wheelchair was parked in a corner and he was walking more often, and those are the kinds of things that matter to us, not how far they can walk in a six minute time period, but more the quality of life. When max started on the trial, they were really looking for these clinical endpoints and they were also looking for dystrophin as a biomarker, which would lead to the knowledge that there was going to be a clinical endpoint met. He was biopsied after 12 weeks and originally they did not see any dystrophin being made, but at the 24 week mark, they saw that it was being made. And I was seeing that he was benefiting. Eventually I started working with some of the other parents in the study to start to bubble that up to the top, that patient experience. And we did a retrospective patient reported outcome study that we were able to thankfully share with the FDA, share with policymakers, and eventually share with payers to say, these things matter. Some of those endpoints we were collecting were, whether patients in the study could lift a glass and drink, whether they were able to do things that mattered to them, use a cell phone, walk for the day at school, and things like that. We really wanted regulators and companies to keep in mind that when there are no treatment options for a fatal condition, we’re not really expecting a cure, but those incremental benefits that stop or slow the progression of the disease are meaningful.

Daniel Levine: You’ve since done a lot of work in the advocacy realm and served as a consultant, how have you seen perceptions of the patient voice and its importance evolve?

Jenn McNary: I can’t believe I’m saying this, it’s been over a decade since Max enrolled in that first clinical trial. And I have seen that the space was completely different back in those early days. I think I’m quoted in some media piece as saying I was going to the FDA to talk. I didn’t even know where the FDA was located. I had no idea what the mechanisms were. There just seemed no path forward for advocates who were truly the ones having experience with the disease and having experience on therapies to have a platform. So now we have ample opportunities to share experiences. We’re invited to patient-focused drug development meetings. We’re invited to seats at the table in the form of advisory boards. We have an advisory board at my company Fulcrum Therapeutics where patients are actually intimately involved in designing protocols and reviewing the endpoints to make sure that the things we’re measuring are meaningful to patients.

Daniel Levine: Today, you serve as head of patient advocacy and engagement at Fulcrum. Fulcrum’s developing therapies for the rare muscle disease FSHD as well as sickle cell disease. What attracted you to work for industry?

Jenn McNary: After working as a patient advocate, really on the front lines of our drug approval for Exondys 51, I started meeting with other patient communities in and outside of Duchenne and realized that there was this opportunity for us to share the learnings. I really truly believe that we should learn from every decision in this drug development process, and we should share information and insights. So, as I started working with some of these other patients and patient groups, drug developers started to approach me to find out what we did. How did we engage over 1500 patient advocates at the FDA? How did we get together and really share a united voice? And what could companies do to make sure that they’re capturing the right endpoints? So, I did start a consulting company that was working with a myriad of rare disease companies. And I got really excited about the opportunity when it arose with one of my clients, which is now Fulcrum Therapeutics. I’ve been working with Fulcrum for the past four years, and I was really involved in the FSHD community. It’s not the same as Duchenne, but this community is kind of where I was when Max started his trials. They are without a treatment. And I met and grew to love the patient community. And I felt like I had an opportunity to share the luck, share that experience that we had going through the clinical trial process, and hopefully be part of bringing another drug to market.

Daniel Levine: As a patient advocate within a drug development company, how do you see your role?

Jenn McNary: So, so my role at Fulcrum is really two-fold: it’s to serve as a liaison to the community from the company. I work as the person engaging the community to bring those insights from the patients back inside, and also to help my colleagues understand what is a meaningful endpoint. What does meaningful commercialization look like and how do we combine our efforts with the efforts of the patient community and truly be partners and advocates in that arena.

Daniel Levine: Even with the advances we’ve seen, I still hear from time to time complaints that industry and regulators don’t take the patient perspective into consideration early enough with regards to trial designs. Do you feel you’ve been able to serve as a conduit for patients to help shape clinical trials early enough in the process where it is meaningful?

Jenn McNary: Let’s be honest, there is so much more work to do, and I don’t think we will ever, ever reach that point where we can say, we’ve done it, we’re doing enough, we’re doing it well, there’s nothing more to do. I think that companies who are doing it right, and I count our company as one of them, are really bringing folks to the table as early as humanly possible. So pre-clinically, starting to talk to communities about natural history studies and learning from the community. Is there an unmet need here? Is there something we can solve for? Is there a want and a drive in the community? Have you started working together as a patient community and really asking all of those right questions? And then as you go through looking at those critical time points in a drug development pipeline and saying, when can we involve and infuse the patient perspective? So, are we doing it perfectly? No, but are we getting better every day? I think yes. And I do think that we will get to a point where patients and caregivers have that sort of professionalized seat at the table at every time point. And I think I’m a walking example of that. I don’t have the medical background that many of my colleagues have. I don’t have the educational background that many of my colleagues have. But what I have is 23 years on the front lines of dealing with a rare disease and multiple clinical trials. And so I think, companies taking that leap to include perspectives like mine are really forward thinking,

Daniel Levine: Well, let’s talk about FSHD, which is Fulcrum’s lead program. For listeners not familiar with the condition, what is it, and how does it manifest itself and progress?

Jenn McNary: I’m always going to butcher the name, but fasioscapulohumeral muscular dystrophy is FSHD and it’s a rare genetic disease that is characterized by progressive muscle atrophy. It typically affects the muscles in the face, shoulders, and upper arms and abdomen, but can also impact the lower body over time. people with FSHD report that they are experiencing pain, fatigue, and of course, difficulty performing activities of daily living. It is one of the most common forms of muscular dystrophy.

Daniel Levine: How are patients with the condition treated today and what’s their prognosis?

Jenn McNary: So currently, like Duchenne when my boys were diagnosed, there are no approved treatment options for FSHD right now. I’m finding that patients are managing it by participating in things like physical therapy, exercise nutrition, and using assistive devices as their tasks become more difficult, such as walkers, leg braces, orthotics, and again, wheelchairs when they progress to that point.

Daniel Levine: Is there an example of how Fulcrum has been able to take the patient perspective and alter its plans for a trial to reflect patient input?

Jenn McNary: Absolutely. So, we’re incredibly proud of REACH, which is our phase 3 that was just announced. It’s a trial in losmapimod, and it really is a good example of including perspectives from our patients into the clinical trial design. We’ve had the privilege and the honor of hearing patient stories and multiple people with FSHD have been engaged with our team in various ways, and so our team worked closely with the FDA and made the primary endpoint of the study the absolute change from baseline in reachable workspace. Reachable workspace measures the upper extremity range of motion and function, and has been shown to correlate with the ability to independently perform activities of daily living. These are important because a lot of the patients that we talk to really want to be able to just be as independent as possible. So, those include filling up a coffee mug and having their morning coffee, being able to put a cell phone up to their ear and have that conversation, being able to complete work tasks. One member of our advisory board talked about being able to hold a bottle for her grandson and feed him. And our trial also will measure the patient global impression of change and quality of life. These endpoints show the importance that we’ve placed on determining losmapimod’s ability to positively impact our patient’s lives.

Daniel Levine: What’s the process you take for doing this? How do you help your company understand things like quality of life impacts of a condition and endpoints that are meaningful to patients?

Jenn McNary: So, constant contact, right? We always have to keep touch points and we have regular meetings with the patient community. In this case, we at Fulcrum have been lucky to work with the FSHD community. They’ve been exemplary in their commitment to engage with us in efforts that can help make treatment options available, and their perspectives have been vital through the drug development process. Since Fulcrum’s Foundation even, the team has been actively engaging with the FSHD community partnership, with the FSHD Society and funding advocacy initiatives. we co-funded the patient-focused drug development meeting PFDD that was held in June of 2020. We provided people impacted with the disease the opportunity to really share their stories with the agency. we also have provided a platform for patients to meet in the format of our advisory board and through that advisory board, several of our advisors work together on their own to develop a white paper that further explains the disease manifestation, and impact efforts like these provide frequent reminders to our team, myself and others, about how this disease impacts patients and what a treatment would actually mean to this patient community.

Daniel Levine: What advice would you have for drug developers as to how they can better incorporate the patient voice in their work?

Jenn McNary: My advice for people working in the drug development space would be that you need to consistently strive to look for ways of incorporating patient experience and voices and be creative—thinking outside of the box to look for those ways that meet the needs of both your company and the patient community that you’re working with. They are not all the same, and they’re not cookie cutter. You have to be creative when you’re working with patients. Make sure that they’re involved in every aspect of decision-making. You need to make sure that you provide them a platform for speaking. And once drugs are approved, making sure that they are accessible. Preparing and planning for that you need to ask these questions of yourselves, what matters, what’s meaningful, and how can we create a treatment or a cure as it relates to what they’re looking for. So, in our experience, slowing or stopping the progression of the disease, and then you also have to look at what aspects of their daily lives are impacted and how can we impact that. And sometimes that goes outside of just your therapeutic, looking at ways to make sure that these patients are living their best lives. You’re really treating the whole person and not just the disease.

Daniel Levine: How about patient advocates? What advice would you have for them so they can be better heard by regulators and drug developers?

Jenn McNary: Well, I think I’m known as being one of the loudest folks in the crowd. I always tell folks that if you want to talk, and if you want to talk to people who are decision-makers that are going to impact your life and that is drug developers, that is folks on the Hill—policy makers and regulatory folks, you want to make sure that you’re reaching out to those right people at the right time, and you learn how to tell your story. Make sure that payers, make sure that regulators understand what it’s like to have a day in the life of a person living with your condition. You are truly the expert in your disease. I may be an expert in caregiving for Duchenne, but even my sons have a different perspective of the disease. And so your voice matters and it is the right thing to do to share your story to the extent you’re comfortable and look for opportunities to engage. Not everybody has to do everything, but everybody can do something. So whether it’s some sort of a click to share, or phone calls, or advocacy days, or it’s sitting on an advisory board of a drug company that’s looking for a therapeutic in your condition, there are ample opportunities, and you just need to look around for them.

Daniel Levine: Jenn McNary, executive director and head of patient advocacy and engagement at Fulcrum Therapeutics. Jen, thanks so much for your time today.

Jenn McNary: Thank you, much appreciated.

This transcript has been edited for clarity and readability.