The recent DCGI approval for Zydus Lifesciences to commence the Phase III clinical trial of Desidustat in collaboration with ICMR has raised hopes that the home-grown oral drug could reshape the treatment of Sickle Cell Disease (SCD), an inherited blood disorder affecting millions of Indians, particularly those from tribal communities.
According to National Health Mission estimates, nearly 20 million Indians carry the sickle cell trait or disease, while about 50,000 children are born with sickle cell anaemia every year.
Hydroxyurea is the current mainstay of treatment besides frequent blood transfusions, both of which have important limitations.
The Desidustat has already shown encouraging results in the Phase II proof-of-concept study conducted jointly by Zydus-ICMR. Under the much larger Phase III trial, the 203-day multicentric study will enrol 164 patients with SCD across multiple centres in India.
It will be conducted as a randomised, double-blind, placebo-controlled trial—the gold standard in clinical research. Neither the participants nor the investigators will know who is receiving Desidustat and who is receiving a placebo, ensuring unbiased assessment of the drug's safety and effectiveness.
The timing of the trial is significant. India has launched the National Sickle Cell Anaemia Elimination Mission, aiming to eliminate the disease as a public health problem by 2047. However, treatment options remain limited.
Hydroxyurea helps reduce painful crises in many patients but does not work adequately for everyone. Long-term blood transfusions improve anaemia but increase the risk of iron overload, infections and repeated hospital visits. Bone marrow transplantation (BMT) offers a cure for a small proportion of patients but is expensive and requires a suitable donor.
Unlike hydroxyurea, Desidustat belongs to a newer class of medicines known as hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitors.
The drug works by stabilising hypoxia-inducible factor, a natural protein that helps the body respond to low oxygen levels. This stimulates the production of erythropoietin, the hormone that promotes red blood cell formation in the bone marrow.
For patients with SCD, who suffer from chronic anaemia because their abnormal red blood cells break down rapidly, improving red blood cell production may increase haemoglobin levels, reduce anaemia and potentially improve oxygen delivery to tissues.
Researchers also hope that better correction of anaemia may reduce fatigue, improve quality of life and possibly decrease complications associated with chronic oxygen deprivation.
While Phase II established preliminary efficacy and safety, Phase III will answer the question that matters most: Does the drug consistently benefit a much larger and more diverse group of patients?
The Phase III trial will evaluate whether Desidustat can safely and effectively improve haemoglobin levels and reduce anaemia in people with SCD over an extended period.
Researchers will closely monitor patients for side effects, overall safety and tolerability while comparing outcomes with those receiving a placebo under a rigorous double-blind, randomised study design.
The trial is intended to determine whether the benefits of the drug outweigh any potential risks. If the results are positive, they will provide the robust clinical evidence required for regulatory approval, paving the way for Desidustat to emerge as a new treatment option for SCD in India.
In fact, Desidustat has already attracted international attention. The US Food and Drug Administration (FDA) has granted the drug Orphan Drug Designation for both sickle cell disease and beta-thalassaemia, recognising its potential in treating rare blood disorders.
The designation does not mean the drug is approved, but it acknowledges its promise and provides regulatory incentives for further development.
For India, however, the significance goes beyond regulatory recognition. Desidustat has been discovered and developed entirely in India, making it one of the country's most advanced indigenous innovations in rare disease therapeutics.
SCD disproportionately affects tribal communities across states such as Madhya Pradesh, Chhattisgarh, Maharashtra, Gujarat, Odisha, Jharkhand and Rajasthan.
Many patients live in remote areas where access to specialist care and regular blood transfusion facilities remains difficult. An effective oral medicine that is easier to administer could significantly improve treatment accessibility, particularly if priced affordably, say the researchers.
ICMR Director General Dr. Rajiv Bahl described the completion of the Phase II study as an important milestone for patients who have limited treatment choices beyond hydroxyurea, saying the collaboration demonstrates the potential of Indian innovation through public-private partnerships.
Zydus Managing Director Dr. Sharvil Patel said the company hopes the drug will address a major unmet medical need and improve the quality of life of people living with SCD.
Experts caution that optimism must be balanced with scientific rigour. For many, promising drugs have produced encouraging early results but failed to demonstrate meaningful benefit in larger Phase III trials.
Nevertheless, if Desidustat successfully improves haemoglobin levels, proves safe and demonstrates meaningful clinical benefit, it could reshape the management of SCD in India.
Until then, standard treatments—including hydroxyurea, appropriate vaccinations, infection prevention, blood transfusions where indicated and regular follow-up—remain the cornerstone of managing the disease.
