Zydus Lifesciences has partnered with the Indian Council of Medical Research (ICMR) to commence a Phase 2 clinical trial evaluating Desidustat, an oral tablet, for the treatment of sickle cell disease. This collaboration seeks to address the significant unmet medical need for effective therapies beyond the current standard of care, hydroxyurea, for the estimated 20 million sickle cell disease-affected patients in India. The trial received approval from the Drug Controller General of India (DCGI).
Trial Design and Objectives
The Phase IIa study is a double-blind, randomized, placebo-controlled, parallel, multi-center trial designed to assess the efficacy and safety of Desidustat in patients with sickle cell disease. Co-funded and co-monitored by the Indian National Clinical Trial and Education Network (INTENT), the trial will measure the proportion of patients achieving a hemoglobin (Hb) response, defined as a ≥1 g/dL increase from baseline, compared to placebo at weeks 4 and 8. Key secondary endpoints include mean change in hemoglobin, proportion of patients requiring blood transfusions, proportion experiencing vaso-occlusive crises, and mean change in percentage of HbSS.
Desidustat Mechanism of Action
Desidustat is a hypoxia-inducible factor (HIF)-prolyl hydroxylase inhibitor. By inhibiting HIF-prolyl hydroxylase, Desidustat stimulates erythropoietin (EPO) production, which subsequently increases red blood cell production under low oxygen conditions. This mechanism aims to improve hemoglobin levels and reduce the complications associated with sickle cell disease.
Addressing Unmet Needs in Sickle Cell Disease
Sickle cell disease poses a significant public health challenge in India, particularly among tribal populations. Current therapeutic options are limited, with hydroxyurea being the primary treatment to reduce the frequency of painful crises. However, hydroxyurea is not universally effective and is associated with side effects such as neutropenia and thrombocytopenia. Blood transfusions, while sometimes necessary, are expensive, not uniformly accessible, and carry risks including alloimmunization, haemolysis, and transfusion iron overload. Desidustat offers a potential alternative or adjunctive therapy to address these limitations.
Expert Commentary
Pankaj Patel, Chairman of Zydus Lifesciences, emphasized the importance of public-private partnerships in healthcare to deliver novel drugs and achieve the goals of the National Sickle Cell Anaemia Elimination Mission. Dr. Rajiv Bahl, ICMR Director General, highlighted the collaboration's significance in advancing clinical research in India and addressing the needs of sickle cell patients beyond current treatments.
