Present Trends in Newborn Screening, Genetic Counseling, and Emerging Drug Therapies in the Effective Treatment of Alpha (α)-Thalassemia in the MENA Region

The occurrence of thalassemia is an issue of major concern in the health sector of certain countries, including the Middle East and North Africa (MENA region), Southeast Asia, Central Asia, and the Indian subcontinent. According to DelveInsight’s analysis based secondary sources, countries in the MENA region, particularly the Gulf Cooperation Council countries (GCC) and the UAE, have a higher  Alpha-thalassemia prevalence than in Europe and North America – the reported prevalence amongst the countries in the region ranges from 2 to 10 %. The condition has also become increasingly prevalent in nonendemic Europe, North America, and Australia owing to population migrations. The issue is, therefore, assuming global significance.

In addition to rising Alpha-thalassemia prevalence, the management of the condition also remains a challenge. In the past, major pharma companies were afraid to enter the Alpha thalassemia market of Africa and certain countries in the Middle East owing to the lack of health care infrastructure to help adequately diagnose and treat patients, which limited the business potential in those otherwise viable markets. However, recent trends point to an increase in genetic counseling, newborn screening, and a significant increase in interest of big pharma giants such as Agios and Silence Therapeutics to capture a fair share of the market for Alpha thalassemia patients in the region.

Current State of Newborn Screening (NBS) and Genetic Counseling in the MENA Region

• Reports indicate that screening for hemoglobinopathies in thalassemia-endemic regions first began in the Mediterranean basin in the latter part of the twentieth century. Greece and Cyprus started their thalassemia prevention programs in the early 1970s with premarital, preconceptional, or antenatal screening. In Cyprus, these programs, which were mandatory or quasi-mandatory, were based on ethnicity. In the Middle East, Israel began performing targeted thalassemia screening of at-risk ethnicities in 1980. By the first decade of the twenty-first century, a majority of Middle Eastern countries had implemented nationwide mandatory premarital thalassemia screening programs.
• The UAE government initiated various measures to reduce the incidence of thalassemia, including the launch of a national campaign in 2008 to promote premarital screening to provide non-instructive genetic counseling to non-at-risk couples. Additionally, since 1995, the Maternal and Child Health Department – Ministry of Health, UAE – has offered newborn screening as a service to families with new babies. Moreover, in 2017, the UAE, based on research and proposal submitted by the UAE Genetic Diseases Association, introduced significant legislation regarding premarital and prenatal screening programs.

• The Thalassemia International Federation has proposed mandatory NBS and maintenance of registries that can catalog the outcomes of screening programs, determine the appropriate Alpha thalassemia treatments, prevention policies, health services, and resource allocation, and guide research related to hemoglobinopathies. The majority of screening programs involve voluntary screening. However, premarital screening is mandatory in the Maldives, Middle Eastern countries, and Cyprus, though decisions regarding marriage and conception are left to individual couples. The other Middle Eastern countries or regions with mandatory premarital screening and genetic counseling programs include Lebanon, Iran, the Gaza Strip, Saudi Arabia, Jordan, and the Kurdistan region in northern Iraq.

Screening programs have now been established in all continents, in both hemoglobinopathy-endemic and hemoglobinopathy-nonendemic regions, targeting either entire national populations or high-risk groups. Increased NBS has turned out to be a pragmatic approach in the MENA region, as it has helped open the window for early detection and treatment of the condition, thereby reducing the healthcare expenditure and cost burden on thalassemia patients and their caregivers.

Updates on Emerging Drug Development in the MENA region

As in the case of the US and Europe, the emerging Alpha thalassemia pipeline in the MENA region is virtually dry as there are only a few key players investigating their products for the patient pool.

• In 2021, Agios Pharmaceuticals initiated its registrational Phase III trials for the evaluation of its key product Mitapivat in the United States, Europe, and Canada. However, the company’s global clinical trials will enroll patients in North America, Europe, the MENA region, the Asia-Pacific region, and Latin America. The company expanded its partnership with Centogene, under which Centogene will provide genetic testing and clinical trial support for Agios’ three global, pivotal trials in thalassemia and sickle cell disease. The collaboration will also offer patients access to genetic testing to help identify causative mutations, including HBA1, HBA2, and HBB genes.
• As per DelveInsight’s forecast estimations and analysis, Mitapivat is expected to benefit from the first-mover advantage, considering that there is no approved therapy for Alpha thalassemia till now. We also expect the drug to enter the US market by 2025. The drug’s potential is attributed to the strong safety and efficacy demonstrated by the drug during clinical development.
• Silence Therapeutics is investigating its product SLN124 in a Phase I trial for the treatment of ‘iron-loading’ anemias, thalassemia, and myelodysplastic syndrome. Recently, the company announced that the first patient was dosed at the Jordan University Hospital, Amman, Jordan, which happens to be one of 25 trial sites for the global, multicenter study, which spans Europe, the Middle East, and Southeast Asia.

In the past, the attention of companies was focused on patients with beta-thalassemia. However, recent years have witnessed a shift in interest of the leading companies to Alpha thalassemia. Owing to the lack of drugs in the region for effective management of the condition, the upcoming therapies by Agios and Silence may give them a first-mover advantage globally, particularly in the MENA region. In this space, it will be interesting to watch the progress of approval and market access of these drugs in the near future.

Progress in Reducing the Burden of Alpha thalassemia in the MENA Region

The growing thalassemia prevalence and its resultant burden is definitely an issue in the MENA region. The problem is compounded by the fact that significant data gaps exist, which come in the way of a proper appraisal of the burden and thalassemia treatment in this region. Therefore, an increase in research and awareness in the field is recommended. Interestingly, in the last decade, the UAE has made significant progress in preventive management resulting in a significant reduction in the prevalence of thalassemia. The mandatory premarital screening program is the most important part of the national preventive campaign against thalassemia. These tests necessitate the public to undergo screening before getting married in the UAE. Moreover, although the emerging pipeline for α-thalassemia in this region is relatively dry at present, physicians and researchers are working rigorously toward increasing awareness, improving diagnosis, and researching for developing novel and potential therapies in the future.

In conclusion, recent years have witnessed an increase in premarital counseling and newborn screening to facilitate early detection and effective thalassemia management in the MENA region. The region holds a vast scope for further advancement in the development of effective therapies at a reasonable cost and their approval and market access!!

References:

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7. Silence Therapeutics. (n.d.). Silence Therapeutics – Silence Therapeutics – First patient dosed in GEMINI II. Retrieved December 28, 2021, from https://silence-therapeutics.com/investors/press-releases/press-releases-details/2021/Silence-Therapeutics—First-patient-dosed-in-GEMINI-II/default.aspx
8. WHO EMRO. (n.d.). WHO EMRO | Expanding the comprehensive national neonatal screening programme in the United Arab Emirates from 1995 to 2011 | Volume 20, issue 1 | EMHJ volume 20, 2014. Retrieved December 28, 2021, from http://www.emro.who.int/emhj-vol-20-2014/volume-20-issue-1/expanding-the-comprehensive-national-neonatal-screening-programme-in-the-united-arab-emirates-from-1995-to-2011.html

Source: DelveInsight – www.delveinsight.com