Latest Global Estimates of Thalassemia Incidence and Prevalence

According to the Global Burden of Disease Study (GBD) 2019, there has been a significant decline in the global burden of thalassemia from 1990 to 2019. During this period, the number of thalassemia incident cases decreased by 20.9%, prevalent cases decreased by 3.1%, mortality cases decreased by 38.6%, and disability-adjusted life years (DALYs) decreased by 43.1%.

Despite this overall decline, thalassemia remains one of the most common monogenic disorders worldwide, with particularly high prevalence in the Mediterranean region, southern China, and developing countries like India, Bangladesh, and Pakistan.

Recent regional data shows varying prevalence rates:

• In Korea, prevalence increased from 0.74/100,000 in 2006 to 2.76/100,000 in 2018, while the incidence rate nearly doubled from 0.22/100,000 in 2016 to 0.41/100,000 in 2018.

• In Baise City, Guangxi, China, the frequency of carriers for alpha-thalassemia is 15% and beta-thalassemia carriers comprise 4.8% of the population.

• A 2022 study in southwestern China found an overall prevalence of thalassemia of 26.76%, with specific incidences of α-thalassemia (17.52%), β-thalassemia (6.92%), and concurrent α- and β-thalassemia (2.32%).

• In Northern Guangdong Province of China, a 2021 study reported hemoglobinopathies and thalassemias at 0.46% and 21.02% respectively, identifying 13.03% α-thalassemia and 6.34% β-thalassemia cases.

• In Iraq, the prevalence increased from 33.5/100,000 in 2010 to 37.1/100,000 in 2015, while the incidence rate decreased from 72.4/100,000 to 34.6/100,000 live births during the same period.

• In Pakistan, a single-center study reported haemoglobinopathies among 28.4% of subjects, with thalassaemia trait (25.6%) being most predominant.

• In Thailand, about one percent of the population are affected with thalassemic diseases, with 30-40% of the population being carriers of at least one abnormal gene.

The global prevalence rate is higher in males than in females, and the global mortality rate shows a consistent decrease with increasing age. Age-standardized rates of incidence, prevalence, mortality, and DALY have declined across regions with different sociodemographic index (SDI) levels, yet remain highest in regions with low SDI and low-middle SDI as well as in Southeast Asia, peaking among children under five years of age.

According to a 2024 study analyzing GBD 2021 data, Southeast Asia exhibited notably high age-standardized mortality, prevalence, and DALYs rates among four Asian regions, while East Asia recorded the highest age-standardized incidence rate.

Despite the overall global decline, notable disparities exist in terms of gender, age groups, periods, birth cohorts, SDI regions, and GBD regions, making thalassemia a continuing major public health challenge in developing countries.

PYRUKYND® (Mitapivat) Clinical Trials Beyond Thalassemia

Indications Under Investigation

Pyruvate Kinase Deficiency (PKD)

• Mitapivat has completed two successful phase III clinical trials demonstrating safety and efficacy in adults with PKD
• The clinical development in adults with PKD is nearly complete
• Mitapivat was approved in 2022 for the treatment of PKD
• It is the first FDA-approved disease-directed therapy for PKD
• In the EU and UK, it is approved for the treatment of PKD in adults

Sickle Cell Disease (SCD)

• A proof-of-concept phase I study showed efficacy in increasing hemoglobin concentrations
• Mitapivat restored the thermostability of PKR, increasing its activity and decreasing 2,3-diphosphoglycerate levels
• A phase II/III trial (RISE UP) is ongoing
• Mitapivat was found to reduce vaso-occlusive crises in SCD
• Mitapivat improves red blood cell survival by increasing ATP and diminishes sickling by decreasing 2,3-diphosphoglycerate

Hereditary Spherocytosis and Other Erythrocyte Membranopathies

• Promising preclinical studies have been conducted
• Suggests potential efficacy in erythrocyte membranopathies
• A phase 2 trial called SATISFY (NCT05935202) is evaluating mitapivat in adult patients with red blood cell membranopathies

Congenital Dyserythropoietic Anemia Type II (CDA II)

• The SATISFY trial (NCT05935202) is also evaluating mitapivat in adult patients with CDA II
• This is a prospective, multicenter, single-arm phase 2 trial involving approximately 25 adult patients

Alpha-thalassemia

• Mitapivat has been evaluated in a phase 2 trial of patients with alpha-thalassemia

Intervention Models

For Sickle Cell Disease (RISE UP Study)

• Double-blind, randomized, placebo-controlled trial with 1:1:1 randomization
• Used a permuted-block method concealed with an interactive response system
• The phase 2 portion was a 12-week trial conducted at 32 clinical sites across 13 countries
• Patients were randomly assigned 1:1:1 to receive oral mitapivat 50 mg, 100 mg, or placebo twice daily
• Both treatment groups showed a statistically significant hemoglobin response rate versus placebo (46% in 50mg group and 50% in 100mg group vs 4% in placebo)
• Registered with ClinicalTrials.gov (NCT05031780)

For Pyruvate Kinase Deficiency

• The systematic review included three clinical trials comprising 94 PKD patients
• Randomization was performed using a permuted-block method and concealed with an interactive response system
• Patients, investigators, and individuals assessing outcomes were masked to treatment assignment
• Phase 3 clinical trials (ACTIVATE and ACTIVATE-T) demonstrated efficacy in improving hemoglobin levels and reducing transfusion burden

Mitapivat offers convenient oral dosing with a safety profile comparable with placebo in adults with PKD, making it a promising therapeutic option for several hereditary hemolytic anemias that currently lack FDA or EMA-approved drug therapies.