Agios' PYRUKYND® (mitapivat) Approved for Thalassemia in Saudi Arabia

Analysis reveals significant industry trends and economic implications

Release Date

2025-08-05

Category

Drug Approval Event

Reference

Source

Breakthrough Clinical Results

Agios Pharmaceuticals announced that the Saudi Food and Drug Authority (SFDA) has approved PYRUKYND® (mitapivat) for treating adult patients with non-transfusion-dependent and transfusion-dependent alpha- or beta-thalassemia. This is the first regulatory approval for PYRUKYND in thalassemia and was granted under the SFDA's Breakthrough Medicines Program. Agios partnered with NewBridge Pharmaceuticals for PYRUKYND's commercialization in the Gulf region. The approval is based on data from the ENERGIZE and ENERGIZE-T Phase 3 trials. Regulatory applications are under review in the U.S., UAE, and EU. PYRUKYND is also approved for hemolytic anemia in adults with pyruvate kinase (PK) deficiency in the U.S., EU, and Great Britain.

Key Highlights

  • First regulatory approval of PYRUKYND (mitapivat) for thalassemia in Saudi Arabia.
  • Approval granted under SFDA's Breakthrough Medicines Program.
  • Partnership with NewBridge Pharmaceuticals for commercialization in the Gulf region.
  • Regulatory applications under review in the U.S., UAE, and EU.

Incidence and Prevalence

Global Thalassemia Burden: Latest Estimates

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. Specifically, 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%.

The age-standardized rates of incidence, prevalence, mortality, and DALY have declined across regions with high, high-middle, middle, and low-middle sociodemographic index (SDI). However, the highest burden remains in regions with low SDI and low-middle SDI, particularly in Southeast Asia, with the peak burden observed among children under five years of age.

Recent epidemiological data reveals that the global prevalence rate is higher in males than in females, while the global mortality rate shows a consistent decrease with increasing age.

Regional studies provide more granular insights into thalassemia prevalence:

In Baise City, Guangxi, China, the carrier frequency is 15% for alpha-thalassemia and 4.8% for beta-thalassemia. A 2022 study from Guizhou Province, China identified 5,099 thalassemia carriers among 26,047 individuals, yielding an overall carrier rate of 19.58%.

In Jiangxi Province, China (2022), among 2,952 children with suspected thalassemia, the overall distribution was 51.96%, with α-thalassemia at 20.86%, β-thalassemia at 30.08%, and concurrent α- and β-thalassemias at 1.02%.

In Huadu District of Guangzhou, China (2016-2021), the detection rate of common δβ-thalassemia/HPFH was 0.19%. A 2017 study in Huzhou region, China found the prevalence of α-thalassemia trait was 1.01% and β-thalassemia was 1.3% among pregnant women, with an overall carrier rate of 2.32%.

In Iran, a study of 678 unrelated α-thalassemia carriers found the most common mutation was -α(3.7) (rightward) (60.9%) deletion.

A 2016 study in the central Andean region of Colombia found the frequency of hemoglobinopathies was 34.5%, with Hb A-Beta thalassemia at 13.91%.

Globally, it is estimated that 5-7% of the world's population carries a significant hemoglobin variant. Beta-thalassemia is reported as the most common monogenic disorder in India.

Thalassemia is described as one of the most common monogenic disorders worldwide, with particularly high prevalence in Mediterranean regions, Middle East Asian populations, and developing countries like India, Pakistan, and Bangladesh.

Despite the overall decline in the global burden of thalassemia, substantial regional variations persist, with the highest burden remaining in resource-limited settings. The most recent data (2024) suggests that systemic interventions including early screening, genetic counseling, premarital health examinations, and prenatal diagnosis should be prioritized in regions with low and low-middle SDI, particularly in Southeast Asia.

Economic Burden

Economic Burden of Treating Thalassemia in USA and Europe

Based on the available research data, there is no specific information about the latest estimates of the economic burden of treating Thalassemia in the USA and Europe within the past five years.

The most recent economic data from other regions includes:

Recent International Cost Estimates

  • Vietnam (2023): The average annual economic burden of Thalassemia treatment was VND 9,947,000 (±6,854,000), equivalent to approximately USD 426.7 (±294.0), with blood transfusions being the main contributor to costs (63%).

  • India (2022): The total annual cost of treating 130 children with beta-thalassemia major in Mumbai was ₹86,72,412 (US$ 127,535) or ₹66,710 (US$ 981) per patient per year. Including intangible costs, this rises to ₹12,82,30,412 (US$ 1,885,741). Direct costs contributed to 94% of the cost of illness with chelation therapy (23%) and blood investigations (21%) being major contributors.

  • Iran (2018): For beta-thalassemia intermedia, the average annual costs of blood transfusion and hydroxyurea in 2015 were 20,733.27 purchasing power parity (PPP)$ and 7,040.29 PPP$ respectively. The effectiveness of blood transfusion was 57.4% while in hydroxyurea group was 60.7%.

  • Iran (2017): The average annual cost per patient was $8,321.8 regardless of the cost of lost welfare. Of this amount, $7,286.8 was related to direct medical costs, $461.4 to direct non-medical costs, and $573.5 to indirect costs.

Older Cost-Effectiveness Data

  • Thailand (2011): An annual average cost of treatment of US$950; 59% was direct medical cost, 17% direct non-medical cost, and 24% indirect cost. Compared with deferoxamine (DFO), using deferiprone (DFP) was dominant with lifetime cost savings of $US91,117.

  • USA (2007): Deferasirox resulted in a gain of 4.5 QALYs per patient at an additional expected lifetime cost of $US126,018 per patient; the cost per QALY gained was $US28,255.

  • Israel (1998): The lifetime healthcare costs of caring for a person born with thalassemia major was estimated at $284,154.

Several studies note that hematopoietic cell transplantation (HCT) costs are equivalent to a few years of non-curative supportive care, suggesting it is justified medically, ethically, and financially for low-risk young children with compatible siblings.

Drug used in other indications

PYRUKYND (Mitapivat) Indications Beyond Thalassemia and Their Intervention Models

Sickle Cell Disease (SCD)

PYRUKYND (mitapivat), a first-in-class oral allosteric activator of pyruvate kinase, is being investigated for Sickle Cell Disease through the RISE UP trial (NCT05031780). This is a Phase 2/3, double-blind, randomized, placebo-controlled trial. In the phase 2 portion, patients were randomly assigned 1:1:1 to receive oral mitapivat at doses of 50 mg, 100 mg, or placebo twice daily. Both treatment groups demonstrated statistically significant hemoglobin response rates compared to placebo (46% in the 50 mg group, 50% in the 100 mg group, versus 4% in the placebo group). Mitapivat's mechanism involves increasing ATP and decreasing 2,3-diphosphoglycerate, potentially decreasing Hb polymerization by increasing hemoglobin's oxygen affinity.

Erythrocyte Membranopathies

For erythrocyte membranopathies, mitapivat is being evaluated in the SATISFY trial (NCT05935202/CTIS:2023-503271-24-01), a prospective, multicenter, single-arm phase two trial. This study involves approximately 25 adult patients (≥18 years) diagnosed with a membranopathy or Congenital Dyserythropoietic Anemia type II (CDA II). The trial employs an 8-week dose escalation period starting with 50 mg mitapivat twice daily, potentially increasing to 100 mg twice daily at week 4. Patients who tolerate mitapivat well may continue in two consecutive 24-week fixed dose periods.

Pyruvate Kinase Deficiency (PKD)

Mitapivat received FDA approval for Pyruvate Kinase Deficiency in 2022. The clinical development program included two key trials: - ACTIVATE: A double-blind placebo-controlled phase III trial in adults not regularly receiving RBC transfusions - ACTIVATE-T: A single-arm phase III trial in adults who were regularly RBC transfused

These trials demonstrated efficacy in increasing hemoglobin levels and reducing transfusion burden.

Hereditary Spherocytosis

Hereditary Spherocytosis is another indication with promising preclinical studies. It is currently being evaluated as part of the SATISFY trial for erythrocyte membranopathies.

Additional Potential Indications

Preclinical studies suggest potential efficacy in various erythrocyte membranopathies. Mitapivat is also being investigated for acquired diseases characterized by dyserythropoiesis and hemolytic anemia.

Alpha-Thalassemia

While the main query asks about indications other than thalassemia, it's worth noting that mitapivat is being evaluated specifically for alpha-thalassemia in addition to beta-thalassemia. In a phase 2 study of non-transfusion-dependent thalassemia, 5 of 5 patients with α-thalassemia had a hemoglobin response.

Across all these trials, mitapivat generally shows a favorable safety profile with adverse events typically being mild to moderate in severity.