What does ‘successful treatment’ look like for patients with rare haematologic disorders? For the thousands currently living with conditions like polycythemia vera, paroxysmal nocturnal haemoglobinuria (PNH), systemic mastocytosis, or haemophilia, existing therapies provide critical relief but often fail to address the multifaceted challenges these patients experience.1–4
As the 2024 Annual Meeting of the American Society of Hematology (ASH) draws near, I want to shine a spotlight on rare haematologic diseases and explore how recent innovations are transforming care while leading to new questions in the field.
A complex puzzle
As Dr. Janis Abkowitz, a past president of ASH, remarked about the challenges facing the field in a recent interview:5
“[W]e are faced with important questions, from healthcare access and equity, to sequencing technology and producing personalised medications, to looking at cost efficacy and risk versus benefit, as well as exploring and developing new drugs and new approaches.”
Rare hematologic disorders, which impact the blood and blood-forming organs, often share these key challenges: delayed diagnoses, demanding treatment regimens, and a significant toll on patients' quality of life. 1–4 Take polycythemia vera, a rare myeloproliferative neoplasm that causes the overproduction of red blood cells, for example. Routine phlebotomies, while essential for controlling haematocrit levels, can be physically draining and disruptive to everyday life, while often leaving symptoms like fatigue and pruritus unrelieved.1
While advances in diagnostics and molecular testing have deepened our understanding of many of these rare diseases, management of these conditions remains a complex puzzle. Despite progress, current standards of care—though vital—often fall short in meeting the full spectrum of patient needs.
Exploring the promise of innovation
Treatments for rare hematologic disorders, once limited to symptomatic management with few therapeutic options, are now at the cusp of a paradigm shift. Advances in precision medicine, gene therapy, and targeted treatments are transforming how clinicians approach these diseases. These developments aim not just to manage symptoms, but to address the underlying causes, moving closer to curative intent.6 But do these novel medicines mark a significant step forward for patients?
Recent innovations, including agents that mimic or enhance the body’s natural regulatory pathways, or target alternative pathways, reflect the growing focus on precision-driven and personalised care – and have created excitement and increased expectations.1,2 For instance, when it comes to PNH, the need for more comprehensive approaches is stark. While complement inhibitors have reshaped disease management by effectively controlling life-threatening intravascular haemolysis, debilitating challenges such as unresolved anaemia and extravascular haemolysis persist in some patients. Emerging treatments that target proximal complement pathways aim to address these shortcomings: reducing treatment burdens, resolving residual symptoms, and providing more tailored solutions to improve patient outcomes.2
Gene therapy is also redefining possibilities for certain rare blood disorders. For the first time, both gene-editing technologies and one-time treatments are being developed—and in some cases, approved— offering curative potential.4,7 In haemophilia, for example, new therapies focus on introducing a functional gene for clotting factor IX, enabling the production of the missing protein and potentially eliminating the need for lifelong infusions. For sickle cell disease, advancements like CRISPR-Cas9 offer patients the chance to imagine a future free from disabling complications and painful crises.7
Perhaps most excitingly, CAR T-cell therapy, initially developed for hematologic cancers, is being explored for rarer non-malignant conditions. While not yet a primary treatment focus, there is interest in adapting T-cell-based therapies to target immune-related disease pathways, though these are still in the early stages.8
Navigating uncertainties
Though the promise of these innovations is exciting, unknowns remain. Important questions about how universally effective these therapies may be can arise. For example, gene therapy or targeted therapies may lead to variations in patient responses, and the potential for resistance adds further complexity.5
Gene therapy, particularly with techniques like CRISPR-Cas9, holds great promise but comes with uncertainties around long-term safety and efficacy. Another important unknown is the durability of gene therapies—whether their effects will last a lifetime or require repeated interventions.7
Lastly, the high costs and logistical demands of these therapies may create barriers to ensuring equitable access for all patients who may benefit from them.2
Looking ahead to 2025
As genetics expert Dr. Joaquim Sá succinctly put it:9
“Precision medicine approaches, such as targeted therapies and gene-editing technologies like CRISPR-Cas9, hold the potential to address specific genetic abnormalities underlying rare diseases, offering revolutionary treatment options.”
In 2024, the pace of innovation in rare haematology has been inspiring. However, while these advancements offer hope for many patients and their families, they also highlight the significant work that still lies ahead for researchers and clinicians.
At TVF, we have extensive experience working across the rare haematology field and are committed to supporting the journey of patients and therapy innovators. If you would like more information on our work in this area, please contact enquiries@tvfcommunications.co.uk.
By Cheryl Kok
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