Gene therapy offers potential to alter thalassemia treatment landscape amid significant clinical development challenges and regulatory uncertainties. Gene therapy is at forefront of emerging curative therapies for thalassemia, with several pipeline products in late-stage trials.
Thalassemia is a rare inherited blood disorder caused due to reduced hemoglobin level and decreased RBC production, leading to anemia. Out of the two main types of thalassemia, alpha and beta, the most prevalent type is beta thalassemia. Around 200,000 people suffer from beta-thalassemia worldwide and the cohort is mostly concentrated in the Mediterranean region, the Middle East, Asia, and parts of Africa and South America.
Majority of beta-thalassemia patients require regular blood transfusions resulting in iron toxicity. The only definitive cure for thalassemia is stem cell transplantation, which has several associated risks and recommended in severe conditions. This indicates that the future of thalassemia market lies in gene therapies. Several companies such as Bluebird Bio, Acceleron Pharma, GlaxoSmithKline, Gamida Cell, Incyte Corp., Bellicum Pharmaceuticals, Kiadis Pharma, Sangamo Therapeutics, and Calimmune are evaluating the safety and efficacy of gene therapies in various developmental stages.
Bluebird holds promise to become a leading player in the market by 2022, considering the latest results from two Phase I/II clinical trials with its lead product, Lentiglobin (BB305), aiming to reduce the number of blood transfusions in 22 beta-thalassemia patients. Post treatment with gene therapy, patients displayed significant improvement, with minimal side effects. Fifteen of 22 patients no longer required blood transfusions and the remaining needed them less frequently. Bluebird is also evaluating the safety and efficacy of autologous hematopoietic stem cell transplantation using LentiGlobin in subjects with transfusion-dependent beta-thalassemia in the Phase III HGB-207 study. The company plans to seek the EMA’s approval for Lentiglobin by 2H18.
Celgene and Acceleron are jointly evaluating the safety and efficacy of luspatercept (ACE-536) in the Phase III BELIEVE trial with beta thalassemia patients and the Phase II BEYOND trial with non-transfusion-dependent beta-thalassemia patients. The FDA has granted luspatercept with the orphan drug status in March 2013 and Fast Track designation in December 2015. The BELIEVE trial met its primary endpoint in July 2018 by achieving a statistically significant improvement in erythroid response to treatment with luspatercept. The companies plan to file for regulatory approvals for luspatercept in the U.S. and Europe in the first half of 2019.
Orchard Therapeutics acquired the rare disease gene therapy portfolio from GSK, which strengthens Orchard’s position as a global leader in gene therapy for rare diseases. Further, potential approvals of products such as Incyte’s Jakafi, Bellicum’s BPX-501, Gamida’s Cordin, and Kiadis’ ATIR-201 will pave the way for gene therapy’s dominance in the developed markets.
In-depth report on global thalassemia market by Grand View Research: