As gene therapies for thalassaemia near approval, India’s healthcare sector must build the right infrastructure, regulations, and payment models to bring cures to patients nationwide. Below, Dr Gandhali Deorukhkar addresses six critical challenges—from facility gaps to long‑term safety tracking—on the path to making gene editing a standard of care.
1. With several CRISPR and lentiviral gene‑therapy candidates now entering late‑stage trials for thalassaemia, what are your projections for first read‑out of pivotal data—and how should hospitals and diagnostic labs in India prepare to integrate those results into clinical practice?
We anticipate pivotal data read-outs for CRISPR-based and lentiviral gene therapies for thalassaemia by late 2025 to mid-2026, depending on regulatory timelines and final patient follow-ups. Once available, Indian hospitals and diagnostics labs must be ready not only with interpretation protocols for molecular outcomes (like VCN, engraftment data, HbF levels) but also with interdisciplinary tumor boards that include hematologists, geneticists, and transplant physicians. Labs must start training on pre-conditioning diagnostics, chimerism analysis, and QC for edited cell products. It's not just about reading the trial results; it's about being institutionally prepared to translate them into patient-ready decisions.
Labs must start training on pre-conditioning diagnostics, chimerism analysis, and QC for edited cell products.
2. Ex‑vivo gene editing requires specialized clean‑room facilities, cell‑processing units, and cold‑chain logistics. From your perspective, what key gaps remain in India’s current infrastructure, and which partnerships (public–private or hospital–industry) will be critical to scaling these capabilities?
India currently has very limited GMP-compliant clean-room facilities outside of a few apex centers like CMC Vellore and select private hospital labs in metros. Cell-processing skills are also limited to stem cell transplant centers, which are not universally equipped for autologous editing protocols. The cold-chain supply chain for apheresis product delivery and cryopreserved return of cells is patchy, particularly across state borders. For these gaps to be filled, we require formal partnerships between hospital chains and biotech companies, preferably with public institutions such as BIRAC or ICMR enabling CapEx subsidies to regional centers of excellence. A hub-and-satellite model, where central facilities process cells while peripheral centers manage apheresis and reinfusion, could be the most scalable approach.
3. India’s Central Drugs Standard Control Organization (CDSCO) is still finalizing guidelines for ex‑vivo gene therapies. What changes or clarifications do you believe are most essential to streamline the IND-to-MA process for thalassaemia gene‑editing products?
Clarity is needed on three fronts:
- Definition and regulation of minimal manipulation versus substantial manipulation of cells;
- standards for comparability and release testing for ex-vivo edited cells, particularly if the cell processing is done abroad and the product is re-imported; and
- the pharmacovigilance expectations for post-market surveillance. Additionally, CDSCO should align more closely with EMA and FDA on orphan-designation pathways and accelerated approvals, especially for single-dose curative therapies.
In my opinion, we need a centralized review board under CDSCO specifically for advanced therapy medicinal products (ATMPs) to fast-track these decisions without compromising safety.
4. Gene therapies often carry price tags in the high six‑ to seven‑figure range. How can payers, employers and government programs design sustainable reimbursement frameworks—such as outcome‑based contracting or annuity payments—to ensure commercial viability and patient access?
In India, upfront reimbursement of ₹3–5 crore is not viable for 99% of patients. We need a hybrid approach—long-term annuity payments, possibly tied to hemoglobin thresholds or transfusion-free status, combined with risk-pooling mechanisms. Payers, including government schemes like Ayushman Bharat, should consider co-pay models with pharmaceutical companies taking deferred payments based on outcomes at 1, 3, and 5 years. Employers and CSR arms of large enterprises could be engaged through disease-specific insurance riders. The National Health Authority could also explore outcome-based tenders for pediatric patients who show biomarkers of high response potential, such as low LIC or low pre-existing alloimmunization.
Payers, including government schemes like Ayushman Bharat, should consider co-pay models with pharmaceutical companies taking deferred payments based on outcomes at 1, 3, and 5 years.
5. Given India’s vast geography and socio‑economic diversity, what distribution strategies (e.g., hub‑and‑spoke models, mobile apheresis units) and patient‑support programs must be in place to avoid concentration of these therapies only in top‑tier metros?
A decentralized apheresis and follow-up network is essential. We should establish regional thalassaemia gene-therapy centers in eastern, central, and northeastern India, areas with high prevalence but low access. Mobile apheresis units, similar to mobile dialysis or blood donation vans, can be piloted under public-private partnerships to reach patients in Tier 2–3 cities. Additionally, patient navigation programs with multilingual counseling, travel logistics, and adherence monitoring will be critical. Non-profits and patient advocacy groups should be formally integrated into care pathways, much like what we’ve done in oncology with Ayushman Bharat empaneled centers.
Mobile apheresis units, similar to mobile dialysis or blood donation vans, can be piloted under public-private partnerships to reach patients in Tier 2–3 cities.
6. Gene‑edited patients require multi‑decade safety and efficacy monitoring. How should healthcare systems, payers and biotech sponsors collaborate to build registries and data‑analytics platforms that track outcomes, manage adverse events and inform future R&D?
This is an area where India must invest proactively. We need a national thalassaemia gene-therapy registry, ideally under the aegis of ICMR or NHM, where every treated patient is tracked for 15–20 years. This should include data points like vector integration sites, reactivation of hematopoiesis, iron overload reversal, and late-onset complications. Sponsors must fund the backend analytics and commit to real-time adverse event reporting. Hospitals, in turn, should integrate this registry into their EMRs and train site coordinators to ensure compliance. This collaborative data infrastructure will not only safeguard patients but also help Indian researchers contribute to global gene-therapy innovation.
We need a national thalassaemia gene-therapy registry, ideally under the aegis of ICMR or NHM, where every treated patient is tracked for 15–20 years.
