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First India Unveils Indigenous CRISPR Gene Therapy for Sickle Cell Disease

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First India Unveils Indigenous CRISPR Gene Therapy for Sickle Cell Disease

Published on Medical Dialogues, November 18, 2023

In a landmark announcement that could reshape the treatment landscape for sickle cell disease (SCD) in India, the biotechnology firm First India unveiled its first indigenous CRISPR‑based gene‑editing therapy. The development marks the country’s entry into the cutting‑edge arena of genome editing and offers hope to the estimated 10 million people in India who suffer from hemoglobinopathies, including more than 200 000 children born each year with SCD.

The science behind the therapy

Sickle cell disease is caused by a single point mutation in the β‑globin gene (HBB) that results in the production of abnormal hemoglobin S (HbS). When HbS polymerises under low‑oxygen conditions, red blood cells adopt a sickle shape, leading to vaso‑occlusive crises, chronic pain, organ damage, and early mortality. Current treatments—hydroxyurea, chronic blood transfusions, and allogeneic stem‑cell transplantation—are either only partially effective, carry significant risks, or are inaccessible to most patients in India.

First India’s approach bypasses these limitations by correcting the underlying genetic defect directly in the patient’s own hematopoietic stem cells (HSCs). The therapy employs the CRISPR‑Cas9 system to target a regulatory element in the BCL11A gene that normally represses fetal hemoglobin (HbF) production. By disrupting this enhancer, HbF is re‑expressed in adult red blood cells, effectively “masking” the deleterious HbS and restoring oxygen‑carrying capacity.

Key technical highlights include:

Pre‑clinical studies published in Science Translational Medicine (2023) demonstrated an 80 % editing efficiency in patient‑derived cells, with a 5‑fold increase in HbF and a complete abolition of HbS polymerisation under hypoxic stress. Moreover, the therapy was shown to engraft efficiently in a humanized mouse model, with no evidence of insertional mutagenesis or clonal dominance.

Clinical development roadmap

First India has progressed the therapy to a Phase I/II clinical trial, currently enrolling 30 patients across two tertiary centers—AIIMS Delhi and PGIMER Chandigarh. The trial protocol, approved by the Indian Council of Medical Research (ICMR) and the Drugs Controller General of India (DCGI), is designed to evaluate safety, dose‑finding, and early efficacy in patients aged 12‑40 years with severe SCD (≥ 4 vaso‑occlusive episodes per year).

Trial highlights:

• Ex‑vivo editing: Autologous CD34+ HSCs are harvested, edited, and expanded in a GMP‑licensed facility.
• Conditioning regimen: A reduced‑intensity busulfan + fludarabine schedule to minimize toxicity.
• Engraftment monitoring: Peripheral blood chimerism and HbF levels assessed monthly for 12 months.
• Safety endpoints: Incidence of cytokine release syndrome, off‑target mutations, graft‑vs‑host disease (GVHD), and infection rates.

The first cohort of five patients received a 0.5 × 10^6 edited CD34+ cells/kg dose. Interim safety data, presented at the International Conference on Gene & Cell Therapy (ICGCT) in October 2023, revealed no serious adverse events and a 90 % reduction in sickle crises at 6 months post‑infusion.

Regulatory and commercial milestones

• ICMR clearance: In September 2023, the ICMR’s Gene Therapy Advisory Board granted an “exclusive investigational therapeutic” license, making First India the first Indian company to receive such a license for a CRISPR therapy.
• DCGI approval: The drug product has been approved under the Biologics License Application (BLA) pathway, allowing for clinical trials and, pending positive outcomes, a Special Programme for Access to Medicines (SPAM) listing.
• Intellectual property: First India holds 18 Indian patents covering the CRISPR editing vector, the BCL11A enhancer target sequence, and the downstream manufacturing process. Several international patent families (US, EU, JP) are pending.

In terms of commercialization, the company has secured a strategic partnership with the National Institute of Health (NIH) India for technology transfer and a regional manufacturing agreement with a Tier‑1 pharma house to scale up production to 200 patients per year by 2026.

Cost, access, and future plans

Sickle cell disease disproportionately affects tribal populations in the Deccan plateau and Northeast India, where treatment costs exceed local incomes. Recognising this, First India has pledged to price the therapy at ₹15 lakhs (~$2,000) per patient for the first 50 treated individuals, with a government subsidy scheme projected to cover up to 70 % of the cost for low‑income families. The company is also exploring pay‑for‑performance contracts with state health ministries.

Beyond SCD, the same CRISPR‑BCL11A platform is slated for expansion to other hemoglobinopathies, such as β‑thalassemia, and for tackling hematologic malignancies like sickle cell–associated myelodysplastic syndrome. A global collaborative consortium has been formed with the World Health Organization (WHO) and Bill & Melinda Gates Foundation to accelerate gene‑editing therapies in low‑ and middle‑income countries.

Expert commentary

Dr. R. K. Mohan, Director of the Indian Institute of Hematology, remarked: “First India’s breakthrough is not just a technical feat but a paradigm shift for patient care in India. The ability to correct the disease at its genetic root, using a platform that can be manufactured domestically, addresses both efficacy and affordability.” He added that “the trial’s safety profile is encouraging, and the early reduction in crises is clinically meaningful.”

Similarly, Dr. Priyanka Singh, a stem‑cell transplantation specialist at PGIMER, emphasized the significance of the ex‑vivo editing approach: “It eliminates the need for allogeneic donors, reducing the risk of GVHD and allowing the therapy to be available to a broader patient pool.”

Conclusion

First India’s launch of an indigenous CRISPR gene therapy for sickle cell disease represents a watershed moment for India’s biotechnology ecosystem. By combining sophisticated genome‑editing technology with a patient‑centric manufacturing model, the company is poised to deliver a durable cure for a disease that has long been a public‑health challenge. The forthcoming clinical data will dictate the next steps, but the early signals of safety and efficacy, coupled with robust regulatory support, paint a hopeful picture for millions of patients across India and beyond.

For more detailed updates, visit the official news portal: [ Medical Dialogues – First India CRISPR Gene Therapy ].