Solving the Rare Disease Equation - Dr. Alaa Hamed, Global Head of Medical Affairs, Rare Diseases at Sanofi


As we continue our focus on rare diseases on Raise the Line, we’re delighted to be joined by Dr. Alaa Hamed, Global Head of Medical Affairs, Rare Diseases at Sanofi, one of the leading pharmaceutical companies in the world. Although most well known for their focus on lysosomal storage disorders including Gaucher and Pompe disease, Dr. Hamed and his team at Sanofi are also working in adjacent disease spaces depending on the systems affected. “For example, the lysosome in Pompe disease affects the neuromuscular tissues, so we have a neuromuscular disorder interest as well.” In their discussion, Dr. Hamed and host Shiv Gaglani also touch on the efforts Sanofi is making to shorten the diagnostic odyssey for rare disease patients, including building more disease awareness and greater global infrastructure. “From the inception, we thought that having universal access is a key part of the rare disease equation.” You’ll also learn about the challenges of drug development, the importance of maintaining policy incentives to focus on rare diseases, and where innovation is needed most to advance outcomes for patients. Mentioned in this episode: https://www.sanofi.com/




Shiv Gaglani: Hi, I'm Shiv Gaglani, and today I'm delighted to welcome Dr. Alaa Hamed to Raise the Line as we continue our focus on rare diseases. Dr. Hamed is Global Head of Medical Affairs for Rare Diseases at Sanofi, one of the leading pharmaceutical companies in the world. In the rare disease space, Sanofi is most well-known for its focus on lysosomal storage disorders, a group of conditions caused by enzyme deficiencies including Gaucher disease, Fabry disease, Pompe disease, Acid Sphingomyelinase Deficiency (ASMD) and Mucopolysaccharidosis type 1. I'm really looking forward to learning more about Dr. Hamed's work in rare diseases and what progress Sanofi is making in its many research efforts. So, Dr. Hamed, thanks for taking the time to be with us today.


Dr. Alaa Hamed: Thank you, Shiv, for the invite. Appreciate being here.


Shiv: We always like to ask our guests to tell us a bit about your background, what got you interested in the field of medicine and then eventually joining Sanofi some years ago?


Dr. Hamed: I'm not sure where to start, but I'll start by birth. I'm Egyptian by birth. I was raised in Kuwait, and I came to the U.S. about twenty-five years ago. I finished my med school in Egypt and then moved to Boston University upon arrival in the U.S. I’ve been with the company for over ten or about twelve years now primarily focused on rare diseases over that period of time. 


How my interest in rare disease started...I would say since a very young age, I was interested in a human aspect of life in general. I was hoping to become a writer and that led me to medicine to begin with, because every patient is a story. Through my evolving career journey, I ended up with the most personal of all specializations which is the disease where truly every patient is a story and we interact on a daily basis with patients that inspire us and compel us to keep moving mountains for them.


Shiv: Yeah, absolutely. We've been honored to be able to profile many patient and family member stories, including with Pompe disease. So, we're coming up on the fortieth anniversary of the Orphan Drug Act, and that's partly why we're so focused on the rare diseases landscape. For our listeners who may not be as familiar with the landscape, how would you describe the current state of the global rare disease ecosystem and some of the major challenges for developing therapies for rare diseases?


Dr. Hamed: I would say it has evolved over the past thirty years. We developed our first drug, Ceredase, about thirty years ago and the filing study was in twelve patients. That's how we got our approvals – a single arm, twelve-patient study. Moving thirty years down the line, one of our development programs in Pompe, the Phase 3 study, is about 100 patients in a randomized controlled study. 


You could see over thirty years the level of evidence and the challenge in generating evidence became more and more complex. But I would say also the incentives that were set in place at the beginning truly accelerated innovations to patients. We need to protect those incentives as the landscape evolves because there are very few stakeholders or industry partners in the patient community that are able to bring therapies to market and continue to bring therapies to market. Keeping those incentive structures in place is really important.


Shiv: Absolutely. That's including the production of new therapies or the R&D that funds these new therapies and repurposing of existing medicines as well. But then there’s access. It's one thing to develop the medicines, another thing to provide access to them. Can you tell us about some of the challenges in helping improve access to these innovative medicines as well?


Dr. Hamed: At the nucleus of Sanofi’s ecosystem from the beginning -- when Ceredase, which was the first product in Gaucher that came to approval -- we started our humanitarian program. From the inception, we thought that having universal access is a key part of the rare disease equation. So, there is access that is for the developed world, and for people who cannot access our therapies we created the Humanitarian Program. In between there is a spectrum because access is not just providing the therapy, but also building an infrastructure that would support the delivery of the therapy. 


Sometimes the Humanitarian Program was the nucleus to build infrastructure and capabilities of countries around the globe. We still continue thirty years on to provide access in numerous countries around the world where the probability of commercialization is very slim, and yet we are committed to providing access. Also, the idea of a global initiative with a local implementation is embedded in rare disease because the patients are few and far apart. You need all patients to collect evidence, you need all patients to understand the condition, and so obviously you also need to deliver the therapy to all patients who need it.


Shiv: I think that's well said. Because sometimes you're dealing with conditions that are one in a million, one in 500,000 where it's truly globally distributed and you have to be able to get the patients registered in these other countries and then the access to the medicines for them. In terms of which rare diseases Sanofi has focused on -- we mentioned lysosomal storage diseases in the introduction -- how do you decide what rare diseases to invest in and what criteria are considered when you're weighing those decisions?


Dr. Hamed: Again, we start from our history. We started with lysosomal storage disorders, and they are a group of disorders around the lysosome. We're talking about the patient as the unit, so now we're talking about the cell and even an organelle within the cell, which is the lysosome. The storage disorders of the lysosome result in different multi-organ manifestations. We started with Gaucher and then we moved to other lysosomal storage disorders including Fabry disease, Pompe, and MPS 1. Most recently, Acid Sphingomyelinase Deficiency. That is where we start at the cell and at the lysosome. 


However, these diseases also have manifestations that affect different systems, different organs, so we look at adjacency to those disease spaces. For example, the lysosome in Pompe disease affects the neuromuscular tissues, so we have a neuromuscular disorder interest. In the case of Gaucher or ASM, it's more on the hematological aspect of the tissues, it's more about the blood picture, the bone marrow, the spleen, etc. In Fabry the organs that are affected are more around the renal, so the kidney or also cardiac. Where the symptoms arise, that's where potentially the next disease area comes to mind. We build organically and opportunistically from adjacencies to where we currently are. That's part of the larger rock that we're chipping on from our end. I know others are chipping from other sides until we eliminate or address this problem for over 7,000 rare diseases worldwide.


Shiv: That's a very sensible approach, I think, to build upon successes and go step by step, as you mentioned. There has been an exponential increase in the development of targets and obviously with new tools like AI to identify targets, and then high throughput drug screening, the landscape seems to have shifted and improved in how we develop and deliver drugs. Can you talk to us a bit about some of those emerging trends within the ecosystem and maybe some of the views that you or Sanofi have on how we can take advantage of those?


Dr. Hamed: Generally, when we move to a new therapeutic area, we would always say we need multiple shots on goal, looking at different modalities in order to address the unmet need. Sometimes each treatment modality would address part of the unmet needs so, yes, the diseases are rare but they are also very heterogeneous in their manifestation. Certain modalities might address some aspects of the disease better than others. Currently, we're developing, for example, therapies that are small molecules as opposed to biologics and a working hypothesis that sometimes small molecules would penetrate harder to penetrate tissues like the cardiac muscle or the bones, etc. 


Also, as you understand the disease more, you also move to the remaining unmet need in the condition. With the unmet need in the condition, you address the visceral component of the condition but, for example, there is still a remaining neurological aspect of the disease. You might look for a blood-brain barrier, a penetrating modality.  Again, science drives where we go but also which science meets which unmet need based on the current condition of the patients and the available therapies.


Shiv: That makes perfect sense. We've talked a lot about drug development and access. One of the major issues facing rare disease patients is the initial diagnosis. The diagnostic odyssey tends to be four to nine years for a rare disease patient. Is there anything that you can comment on as far as what you all have done at Sanofi in terms of shortening or improving the diagnostic odyssey?


Dr. Hamed: Also from the inception, one of our key prerogatives was how to make sure that patients who are floating in the system get diagnosed. That starts with disease awareness and building awareness around the conditions because they tend to be under the radar for most of the practitioners. It includes supporting deep expertise in centers of excellence. It includes developing specific testing or easier testing in certain conditions, pioneering simpler approaches like a dry blood spot, for example. It includes innovation -- digital innovation at this stage -- algorithm development in order to try to find the patients who are floating in the system undiagnosed. 


It also includes building a global infrastructure or supporting the building of a global infrastructure in testing and specialized testing labs and samples that move across the globe for a proper diagnosis. It also includes supporting reference networks and there are multiple initiatives that are happening independent of us, but we also help facilitate those networks of reference and sharing of knowledge. It's a global village in terms of rare disease and we're a catalyst in that village.


Shiv: That’s great. Considering the holistic patient journey, it makes a lot of sense. That's clearly something you guys have thought about. You've been at Sanofi for twelve years. You've mentioned that the first drug in this area was about thirty years ago for lysosomal storage disorders. What are some of the things over the course of your tenure at Sanofi that you're most proud of?


Dr. Hamed: I think our most recent products that we brought to market, Olipudase alfa and Alglucosidase alfa. For me, it's a personal journey because when I joined the company, these products were in the design phase for their Phase 3 study. So, I had the opportunity to be part of the brainstorming and the conversations that we had with authorities across the globe about what kind of endpoint, what are the right sizes, etc. I saw the trials evolve and the challenges we faced during the trials, and then the challenges in interpretation of the data and understanding what the data means, and eventually getting a label. 


In the case of, Olipudase alpha, for example, we had an accelerated approval path almost across the globe. It was probably the only product that the company had at that time that had PRIME, which is the accelerated approval path in Europe; it had Sakigake which was the accelerated approval path in Japan; and it had also a U.S. accelerated approval from the FDA. Actually, the team submitting simultaneous accelerated submissions to multiple, global bodies at the same time was something amazing to watch and to be part of. But again, the final thing is that we brought a therapy to market. It was the first therapy to market and suddenly those patients who've been waiting for thirty years patiently -- about twenty years of development in this specific area -- now we have a product to serve their unmet needs. That was, from a professional standpoint, very fulfilling and very rare. Currently, we tend to move around a lot. If you end up seeing a story from beginning to end -- back to stories -- it's something that has a meaning to it, so it's a privilege to be part of that story.


Shiv: That sounds incredibly fulfilling to go through that journey from start to finish. For our audience, many of whom are current or future healthcare professionals, the landscape of healthcare and medicine is changing pretty fast. COVID certainly accelerated some of those trends like telehealth or digital health, retail getting into medicine, etc. We just had the Chief Medical Officer of Walmart Health and Wellness on the podcast last week, as an example. I'm wondering if can you describe your day-to-day role? What does it look like in your role for those who are interested in going into medical affairs or being chief medical officer at life science company?


Dr. Hamed: The day to day there is a lot of separate conversations and separate work streams. You have to be good at multitasking, compartmentalizing and jumping deep from one topic to the next almost every thirty minutes or every hour. But that's a skill you develop with time – how you can be broad and be deep and also be able to switch channels in your brain fast. 


There are multiple themes in medical affairs and we touched upon a lot of them. But you could see throughout the development continuum of a condition, starting with understanding the natural history, designing the right natural history studies, trying to figure out what could be a potential endpoint for a study, building the relationship with a treated community and understanding where existing expertise lies within the community because for rare diseases, the expertise could be a cluster in South America or a cluster in Paris or elsewhere. 


Being part of a global medical affairs function, you pivot across the globe where the expertise is and where the patients are. Sometimes you are the connector between all the expertise. We actually do have advisory boards as part of our daily activities. These advisory boards are focused on a multiplicity of topics. But that's where you bring experts from across the globe to advise on a specific challenge. You also think a lot from a patient-centric standpoint about the unmet need and how would you fulfill that unmet need. What kind of evidence do I need to generate? Specifically in rare diseases, we have registries. Sanofi is fortunate to have the largest lysosomal storage disorder real world data set currently in the world. That in itself creates a lot of opportunities to still understand and evolve our understanding of the conditions that we study. 


There is a component in medical affairs also, as we mentioned, around diagnostics and around all aspects of the diagnostic endeavor from pure service delivery to operational aspects to actually publishing insights on analyzing data. It's a very fulfilling profession where you could also, if you're interested in strategy, you could practice that. And in being part of a large pharma company, you could also see how you could use the muscles and the reach of the larger organization to fulfill the patient unmet needs. That's a very unique situation as well, that I’m privileged to be in.


Shiv: Absolutely. That sounds pretty exciting. A bit daunting for how many hats you have to wear and how many things you could be doing, but also very exciting, especially when you see a drug from start to finish. What advice would you give to our learners about approaching their careers in healthcare and medicine, pharma, etc.?


Dr. Hamed: I would say, follow your heart. Sometimes you will be in a place where you're not sure exactly what your story is and how it's going to evolve, but you will realize the meaning in due time. When you're going through hardship, you keep going. Don't give up and be steadfast. Always remember why you came to this profession and follow your heart, but also stay the course and it will lead you where you are meant to be led.


Shiv: That's awesome, tried and true advice. Thanks for that. Just to be respectful of your time, I only have two other questions. The first is, as you may know, Osmosis is a teaching company, and we like to fill in knowledge gaps. If you could teach any group of people anything, what would it be and why?


Dr. Hamed: Interesting question. What are the needs of your stakeholders? I would start with that if I'm designing a curriculum. What are the needs of the audience? If the need is science based, then definitely I would try to teach more around the rare disease ecosystem in general and also on our conditions, and raise awareness and use your channel to raise awareness on the diseases. If the need is more around soft skills, then I would be happy to also share because they go hand in hand -- the heart, the mind and the soft skills. I would ask you what are the needs of your audience? But I'm happy to share anything.


Shiv: Yeah, we could talk for hours about the different audiences. From our part, we're obviously very interested in trying to fill in the knowledge gaps around rare diseases to get more current and future healthcare professionals and researchers interested in the field. Particularly knowing that rare is actually common. In aggregate, these 7,000 conditions, as you well know, affect hundreds of millions of people directly and then their families as well. It's important work that you all are doing and leading. What else should I have asked you that you'd like to get across to our audience? Anything else top-of-mind or looking ahead that you're excited about that you'd like to share?


Dr. Hamed: I think maybe I’d emphasize a little bit about the headwinds that we're facing in general around rare diseases. As I said at the beginning, we got where we are because of certain incentives that were set up in the system. The thinking that drove this to fruition was the incentives mechanism that were set up in place. At this stage, I would say, there are several headwinds that might make it more and more difficult for rare disease treatments to continue to be developed. It's still a call to action from all the stakeholders. 


We still need innovation, not just in terms of molecule and platform but innovation in regulatory science, innovation in trial design, innovation also in health technology assessment with regard to rare disease. Innovation is not just limited to disease modalities, but it's also into thinking how we can continue to co-create together as partners in the ecosystem -- public and private, patients and industry, and all the other stakeholders and decision makers in the system. Because that's the only way we can solve for more rare diseases and keep chipping at that block.


Shiv: That's a really helpful note to end on where these challenges could be opportunities for our listeners to get involved and do their part to, as we say, raise the line and strengthen the healthcare system. With that, Dr. Hamed, thanks so much for taking the time to be with us today and more importantly, for the work that you and your team are doing to help millions of patients worldwide who suffer from these conditions.


Dr. Hamed: Thank you, Shiv. It's a pleasure to be here.


Shiv: With that, I'm Shiv Gaglani. Thank you to our audience for checking out today's show. Remember to do your part to raise the line and strengthen the healthcare system. We're all in this together. Take care.