ASH sickle cell disease research priorities address pain, organ dysfunction, drug development
Key takeaways:
- ASH issued sickle cell disease research priorities that address seven key focus areas.
- Topics include end-organ dysfunction, pain research and development of new treatments.
American Society of Hematology has issued new sickle cell disease research priorities, highlighting seven key focus areas for maximum impact and benefit to patients.
The priorities will serve as a roadmap for promoting sickle cell disease research, educating providers and enhancing standards of care over the next 5 years.
The seven key areas — which ASH formulated in collaboration with a range of researchers and health care providers — include:
- assessment, prevention and treatment of end-organ dysfunction;
- enhancement of pain research;
- optimization of treatments like hydroxyurea, blood transfusions and approved pharmacologic therapies;
- development of new drug therapies;
- improvement of curative therapies through continued investment into different approaches to partial matched transplants;
- evaluating the impact of evidence-based guidelines to expedite adoption of evidence-based therapies and care delivery; and
- expansion of research into sickle cell trait.
ASH also plans to focus on implementation science by seeking input from patients and their families, according to Betty Pace, MD, who served as co-chair of the working group that developed the research priorities.
“There are issues that we haven’t addressed very well in the research arena, and one is bringing the individual with sickle cell disease and their families more into the picture and getting their feedback,” Pace, professor of pediatrics at Augusta University, told Healio. “We have our thoughts about it as researchers, but patients may have a completely different perspective. We’re continuing to work on incorporating their perspective.”
Healio spoke with Pace about the need for these research priorities, as well as the impact they may have on research and care.
Healio: What prompted ASH to update its sickle cell disease research priorities?
Pace: The research priorities for sickle cell disease were initiated about 7 years ago. There has been a lot of progress in the field over the last 4 years or so, so we felt it was time we brought them up to date. In the last 5 years, there has been progress in gene therapy and with new drugs not previously discussed in the priorities. People around the world look to ASH for guidance on these topics, so we wanted our priorities to reflect where we are in the field.
Healio: What are ASH’s priorities in terms of gene therapy research?
Pace: FDA approved the first gene therapy for sickle cell disease in December 2023, but we still have a long way to go to implement it and make it truly accessible to individuals with sickle cell disease. We are continuing to look at the safety issues related to gene therapy, how we can make it more tolerable and how we can develop newer preparation regimens.
We also want to look at newer technologies coming out that may be safer than CRISPR-Cas 9. Gene therapy will be a very important priority going forward.
Healio: What are ASH’s research priorities as far as optimizing existing and new drugs?
Pace: Optimizing what we have is another important priority. Hydroxyurea is the standard of care now, and it has been approved for sickle cell disease since the late 1990s. It didn’t initially have a good uptake, but now, with the re-education of the sickle cell disease community, we have a very good uptake.
Hydroxyurea is not a perfect drug — there are issues with it, but it does work. We want to start to develop other drugs that can be combined with hydroxyurea as we move into the era of combination therapy for sickle cell disease.
Over the last 5 years, we have developed new drugs that have been FDA approved for sickle cell disease. We had hydroxyurea for 2 decades, and then we got crizanlizumab (Adakveo, Novartis), which is an IV drug developed for acute pain. L-glutamine, an oral therapy, produced limited efficacy in clinical use.
We are very excited about voxelotor (Oxbryta, Pfizer) because it gave us the first drug we could potentially use for combination therapy with hydroxyurea. We were disappointed when the drug recently was pulled from the market in the U.S. due to safety concerns. We need to keep moving forward, looking at different approaches to developing more drugs that increase fetal hemoglobin and treat other symptoms.
We also want to use things like artificial intelligence to evaluate drugs and find efficient ways to combine them before we take them to the clinics.
We also want to make improvements to blood transfusion, which is a mainstay of sickle cell disease treatment. We’re learning a lot about blood transfusion immune responses. Quite a bit of new research is being done in this area, and it’s an ongoing priority.
Healio: How is pain management in sickle cell disease addressed in the research priorities?
Pace: Pain is one of the most devastating complications people with sickle cell disease deal with daily. The good news is that early gene therapy outcomes alleviate acute pain. There is some chronic pain that will take time to resolve. We want to develop non-narcotic drugs for the kind of pain that is specific to sickle cell disease. It’s not just a general pain — there is damage to the nerve — so we must develop specialized drugs, rather than general opioids like morphine.
Healio: Is there anything else you would like to mention?
Pace: We still have much work to do to understand sickle cell disease and its different complications, like end-organ damage. It’s probably better to approach these challenges from a preventive perspective. We must start treatments with drugs like hydroxyurea in young children to prevent organ damage. Progress has been made, especially over the last decade.
The last area we want to address that is very important is sickle cell trait. We need to do more research to understand sickle cell trait, since we don’t have enough studies to educate them about the true risk of complications. We need more research to be able to inform patients intelligently. This is a high-priority area that is now receiving much needed attention.
Reference:
- American Society of Hematology. ASH announces sickle cell disease research priorities to accelerate treatments and comprehensive care (press release). Available at: https://www.hematology.org/newsroom/press-releases/2024/ash-announces-sickle-cell-disease-research-priorities. Published Sept. 25, 2024. Accessed Nov. 22, 2024.
For more information:
Betty Pace, MD, can be reached at bpace@augusta.edu.
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