Exploring Patient-Reported Disease Burden and Unmet Needs

Biree Andemariam, MD: I think another area of unmet need is pregnancy. [Concerning] many of the agents that we have and possibly agents that we have in the future, they’re not tested specifically in pregnancy. I think there’s an undue burden on women with sickle cell disease that at some point in their life when they want to get pregnant, they have to come off of most therapies. And that’s a burden in and of itself. I think chronic pain is something that is very much understudied, but is a huge burden, particularly for adults living with sickle cell disease. Just curious, Nirmish and Elna, if you have other thoughts, and what are you hearing from patients, maybe directly about what they think are the unmet needs in sickle cell?

Nirmish Shah, MD: I think one unmet need that we’ve kind of alluded to, in some way, is to try and prevent complications, to prevent issues in the first place. And I think that hydroxyurea, as of right now, is the only medicine that we have that’s prophylactic, we’re using it before patients even have issues. The other medicines that we have in our bag of choices are all reactive, if they have pain, here’s an option, if you have hemolysis, here’s an option for anemia. And I think the data is not there yet. But I think an unmet need is to continue to focus on prophylactic therapy, [and] how can I prevent complications long-term? And I think that regarding your point, we don’t just want pain to be reduced. We want it to go away, and we don’t want patients to have pain at all. And hence, I think that’s one unmet need that I think that as a provider, and just talking to patients that, they’re happy that they can have fewer issues. But that’s some of the reason patients are not as adherent with hydroxyurea is that, inevitably, at some point, hydroxyurea works really well, but then it doesn’t. And then, the patients start to give up on it. They say, “Oh, well, it’s not working, because I’m starting to have pain.” And then, the adherence becomes an issue. Thus, I agree that continuing to work on multidrug therapy, chronic pain, and pregnancy, I think all of the above are great points for future attention.

Elna Saah, MD: Yes, I have no choice but to agree. And chronic pain is one of my major interests because it not only impacts the function when they become adults. I have seen in my transition practice that it really does impact their success in transitioning. Because if you are not able to manage their pain and get beyond that, not just the acute pain crisis, but that daily debilitating pain, which impedes their quality of life, then nothing else really becomes a priority—them getting themselves to be pain-free and to be able to function. We have that. Some of the other things that we think about, are basically, from the system standpoint, systemwide issues, and then individual issues and then hematologic issues. I think I’ll start with hematology. From our standpoint, we all agree we have a few more agents besides hydroxyurea, and there are more things in the pipeline. And as you said, we have to think about synergy and multidrug, just like how they did for oncology. And today, childhood acute lymphoblastic leukemia is mostly a cured disease. We have to do that. And the only way we can do that is by having validated end points, all the things we talked about. Validated biomarkers—developing biomarkers, testing them and validating them, and then incorporating them into well-designed randomized control trials with sound end points to say: “this combination and this combination of enzyme agent, plus the fetal inducer, plus a hemoglobin polymerizing agent, produces these changes in this validated endpoint.”

And then, you take a lot of this subjectivity out of it and that improves the dice game, and we can have well-designed algorithms using AI and other things to now say “All right, this is efficient, almost precision-type medicine, precision-type hematology for these patients.” That is, for me, the Holy Grail, from the hematology and the bench now translating to the bedside. And then, once we do that, on the patient side to quality of life, and you talked about chronic pain, and also quality of life, what about cognitive issues? Neurological function, cognition, memory, that is another thing that impedes them from functioning. Thus, those are the few that I can put in that system, why? The access to care and making increasing adult and hematology providers, increasing awareness, but we haven’t done well with the echoes for sickle cell disease. How do we create a wheel and spoke because most of the patients do not reside next to big fancy centers like we have. We have patients in the communities and in rural areas so how do we get these sophisticated treatments all the way out there to where the patients are?

Biree Andemariam, MD: I think you’re absolutely right. We need those models of hubs and spokes, where, we can reach the patients everywhere—everywhere they are living with sickle cell disease. Because, you’re right, Elna, if you’re not living close to a center of excellence, or have an expert close to where you live, then you’re left to your own devices and working as well as you can maybe with a primary care physician or general pediatrician, who don’t have necessarily the same skill set that we do as hematologist and same understanding of the drugs that we have available, how they work in combination based on our real-world experience, and what the pipeline is. I 100% agree with that. That is a major unmet need, particularly for adults with sickle cell disease in the United States. And hopefully, some of those hub-and-spoke models can be developed, and we need the funding to do it. But for sure, we need to do that.

Transcript edited for clarity