The Middle East contains one of the world’s strongest concentrations of expertise in the rare blood disorder thalassaemia. The story starts with the high prevalence of this disease in the region – thalassaemia affects roughly one in 100,000 people globally but reaches up to ten percent of the population in certain Middle Eastern countries – but has been developed by a handful of pioneering haematologists. These physician-scientists have helped change the treatment paradigm for an often-devastating illness which, in its most severe form, can cause bone deformities , an enlarged spleen, delayed puberty, jaundice, and slow growth. For other clinicians and researchers – especially those also working on rare diseases out of less-heralded regions – there is much to learn from the Middle Eastern thalassemia story, covering everything from R&D to data generation, clinical trials, and patient access.
In the Region, for the Region
Dr Ali Taher of the American University of Beirut – today recognised as perhaps the preeminent authority on thalassaemia – has been involved in the field for over 30 years. His interest in the disease, and the inadequacies of the available treatment options at the time, was piqued while working at the Royal Free Hospital in London in the early 1990s where he noticed “a steady stream of Arab patients seeking second opinions on their conditions.”
Returning to his homeland of Lebanon in 1993 with a determination to improve the situation for thalassaemia patients in the region, Taher was the driving force behind setting up a clinical research unit in the country focused on thalassaemia. Many of the prevention and treatment advances for thalassaemia over the past three decades have emerged from the centre’s work, which – as Taher’s protégé Dr Khaled Musallam explains – started from building a “structured understanding” of the drivers of morbidity and reduced life expectancy for thalassaemia patients in the region.
“Rather than accept established definitions [most of which were based on research from Europe or the US and which did not necessarily match the large patient cohorts in the Middle East -ed.], we began to build longitudinal cohorts to define natural history, quantify risk, and identify modifiable factors,” explains Musallam, who now holds several roles within the Burjeel group based out of Abu Dhabi.
“These programmes were conceived from the outset as genuine international partnerships – with centres in Italy and the US – rather than regional participation in someone else’s agenda,” says Musallam. Over time, the data generated began to reshape how the field understood the disease itself. The old label of ‘thalassaemia intermedia’ gave way to a more clinically useful distinction between transfusion-dependent thalassaemia (TDT) (in which patients require blood transfusions every three to five weeks for life) and non-transfusion-dependent thalassaemia (NTDT) (patients who produce enough haemoglobin to survive without regular transfusions) – categories that reflected how patients actually behaved, and that proved critical for both care and trial design.
Perhaps most significantly, the work challenged the long-held assumption that NTDT was inherently mild. Serious complications including thrombosis and pulmonary hypertension were documented, and chronic anaemia combined with progressive iron overload were shown to be clinically meaningful, even in patients who were not receiving regular transfusions. “We were not just describing what we saw,” Musallam notes. “We were building the evidence base that would eventually change how the disease was defined globally.”
The research programme has translated into tangible therapeutic advances. Luspatercept — a subcutaneous injection given every three weeks that promotes red blood cell maturation — was the first novel disease-modifying therapy to reach approval, delivering clinically meaningful reductions in transfusion burden. It has been followed by mitapivat, an oral agent that tackles the disease at a different point in the same pathway, reducing ineffective red cell production and lifting haemoglobin levels in non-transfusion-dependent patients while also easing transfusion requirements in those who depend on them. Mitapivat has recently received FDA approval, with registration in Saudi Arabia and the broader Gulf region to follow. A third agent, sponsored by Novo Nordisk, is now entering Phase III trials at Taher’s institute in Beirut.
Gene Therapy Promise; Access Anxiety
Excitingly, there are also now gene therapies which add yet another treatment option for thalassaemia patients. The Middle East’s most developed economies have thus far been keen to integrate these new products into their healthcare systems.
“Our haematology division is establishing advanced ex vivo gene therapies for both sickle cell anaemia and thalassaemia,” says Tawfeg Ben-Omran, division chief of genetics and genomic medicine at Sidra Medicine in Qatar. “Ex vivo therapy involves extracting stem cells from the patient, treating them genetically outside the body, and carefully reinfusing them. This represents a highly sophisticated cellular approach that will significantly impact the global treatment paradigm.”
“The first CRISPR-based gene editing therapy that allows precise modification of DNA is now available to our population because of the prevalence of sickle cell disease and thalassaemia here,” adds Noura Khamis Al Ghaithi, undersecretary of the Department of Health Abu Dhabi. “Precision medicine changes what is possible, particularly for the serious genetic conditions prevalent in our community. We have consanguinity; we have a higher prevalence of inherited genetic diseases. Precision medicine at population scale allows us to address these directly.”
While both Taher and Musallam are enthused by the promise of gene therapy, both warn of the dangers of solely pursuing cutting-edge gene therapies that cost millions of dollars per course of treatment, placing them out of reach for the majority of the world’s patients.
“We spend a great deal of time discussing gene therapy and the most sophisticated novel agents but approximately 80 percent of thalassaemia patients globally live in low- and middle-income countries where access to even the most basic treatment – safe transfusions and effective iron chelation – cannot be taken for granted,” notes Taher. “I am not proud of a situation in which we celebrate the frontier of science while the majority of our patients are excluded from its benefits.”
He continues, “If the resources required for a single gene therapy case in a resource-limited country could instead provide years of safe, high-quality transfusion and chelation care to many patients – supporting their growth, their education, their capacity to build a life – that is a question of allocation that the field and its funders are obliged to engage with seriously.”
Musallam sees an important role for academic networks in filling the gaps. “While continued investment in advanced cell and gene therapies remains essential, a truly global strategy must also address the needs of patients in regions where such innovations will remain unaffordable. That requires academic leadership rather than commercial drivers.”
For Musallam, drug repurposing is just one practical example. “Older, off-patent agents with plausible biological mechanisms are already being used empirically in parts of the world, but without the clinical trial evidence required to support wider adoption. Pharma will not re-open development programmes for these molecules, which places the responsibility on academic networks to generate rigorous data.”
More unified patient data sets will also help in resource allocation. “Rather than applying a high-cost therapy universally when only a proportion of patients will respond optimally, we should be identifying the clinical and molecular variables that predict response and directing resources accordingly,” adds Taher. “This is personalised medicine in its truest sense – not simply deploying the most sophisticated available tool, but matching the right intervention to the right patient, and ensuring that those who do not require the most expensive option receive excellent, appropriately targeted care instead.”
Lessons to Follow
What lessons are there for researchers in the Middle East and elsewhere working on other rare diseases, or in poorer and even conflict-afflicted environments? Musallam suggests that the models developed around thalassaemia that have helped the Middle East assume a global leadership role are “inherently transferable because they are grounded in patient concentration rather than infrastructure alone.” He continues, “In rare diseases, patient numbers remain the primary driver of evidence generation, visibility, and ultimately investment. Where conditions cluster geographically, the opportunity lies in identifying and organising those populations through registries, cohorts, and shared research agendas.”
For Musallam, a stronger network will be key to capitalising on the successes seen so far, especially around clinical trials. “Industry confidence in the region has grown, supported by improving regulatory frameworks and operational efficiency, yet trial activity remains modest because collaboration is inconsistent,” he states. “A single centre offering a handful of patients rarely justifies the cost of initiating a study, whereas a coordinated group of centres presenting a consolidated cohort becomes immediately attractive. The principal constraint is therefore not capability or readiness, but networking culture.”
Networking is also crucial for Taher, and one of three pieces of advice he gives to counterparts in other specialties and countries looking to build a comparable depth of expertise in a rare disease. “My connections with colleagues in London, Milan, and the US have been as important to everything I have built as anything I have done within Lebanon itself,” he notes. The other pillars are passion – “you must be genuinely drawn to the field you choose, because the depth of commitment required to make a real contribution to a rare disease over a career is not sustainable without it” – and focus – “If you are serious about a rare disease, commit to it fully. Your patient volume will be lower, and your income may reflect that, but the distinctiveness of your academic contribution will be of a different order than if you had chosen a condition present everywhere.”
