For many years, conventional medical approaches involving medication and surgery have significantly enhanced individuals’ well-being. However, certain diseases persist without a definitive cure, and these conventional modalities merely manage symptoms rather than addressing the underlying cause, thus lacking a true remedy for such ailments. This treatment paradigm is particularly pertinent in managing monogenic diseases, arising from mutations in single genes present from birth. It is estimated that over 6,000 such conditions afflict more than 350 million individuals globally.

In contrast to conventional interventions, cells and genetically modified therapies represent a paradigm shift, as they constitute “living drugs” capable of regenerating and replacing damaged tissues, offering potential cures for these range of diseases.

In India, there is a significant drive towards advancing cell and gene therapies, particularly for diseases such as blood cancer. Notably, startups like Immuneel Therapeutics are gaining global acclaim for their endeavors in this domain. Their primary focus is to enhance the affordability and accessibility of these therapies for patients with limited treatment options. One notable trial undertaken by Immuneel, known as IMAGINE, represents the inaugural Phase 2 study of its kind in India for a form of CGT known as CAR-T cell therapy. Its promising outcomes have garnered considerable attention worldwide, serving as a catalyst for further innovation both within India and on a global scale. These trials are instrumental in addressing the medical needs of patients who were previously underserved. India boasts a wealth of biotech talent, underscoring the importance of harnessing these capabilities to pioneer new treatments. Collaboration among diverse organizations and experts is paramount in expediting the dissemination of these therapies to a broader populace.

The transition from conventional cancer treatments to advanced therapies underscores our continuous quest for improved patient care. With biotech firms spearheading efforts to enhance the accessibility and affordability of these treatments, there is renewed hope for patients worldwide, particularly those grappling with severe ailments like cancer. This heralds an era of remarkable progress in medical innovation.

Cell and gene therapy (CGT) represents a highly complex and precision-based therapeutic domain, fraught with challenges. However, amidst these complexities, viable solutions exist.

Some of these challenges and their way out are:     

1. Limited Clinical Success: Despite the promise of cell and gene therapy, achieving clinical success has been constrained due to its novelty and inherent risks. However, continuous research and advancements offer avenues for improvement.

2. Need for Expertise and Infrastructure Development: Academic institutions, research centers, and pharmaceutical companies require ongoing investment in expertise and infrastructure to keep pace with the rapidly evolving field. Regular updates necessitate continuous learning and adaptation.

3. Affordability: Affordability remains a significant challenge for patients in India. Eyestem Research endeavors to address this by offering cell therapy for Dry Age-Related Macular Degeneration at an affordable price point of $10,000 or 8 lakhs per injection. Their innovative approach enables cost reduction through efficient cell production protocols.

4. Insurance Coverage: Limited insurance coverage for CGT products presents another obstacle. While some insurance plans such as, HDFC Ergo Optima Secure, HFDC Ergo Optima Restore, Care Supreme and Care Plus, cover genetic disorders and certain cancers, broader coverage is needed. The waiting period is between 3-4 years for all the plans and the coverage varies for different plans and is ranging from 3L-200L. Emulating innovative financing models from the US, such as outcome-based payments in which the company is only reimbursed (or paid a portion of full reimbursement) if the patients achieve predefined outcomes after treatment, mortgage-like payments, performance-based annuity payments, and employer-sponsored programs, could broaden insurance coverage in India.

5. Logistics Costs: High logistics costs, particularly related to cold chain requirements for transporting and storing CGT samples, contribute to overall therapy expenses. However, the presence of stem cell banks in India, such as Reliance Lifesciences Pvt. Ltd., Cryobanks International India Pvt Ltd, Regenerative Medical Sciences Pvt. Ltd. which stores stem cells between 50,000-80,000 INR which is quite low as compared to US and Australia where the costs are 1000$-3000$ and 3000$-4000$ respectively, thus, offering comparatively lower storage costs aids in mitigating this challenge.

6. Regulatory Approval Timelines: Despite improvements in regulatory frameworks, challenges persist in regulatory approval timelines. Streamlining regulatory processes is essential to facilitate timely access to innovative therapies while ensuring safety and efficacy standards are met.

Moreover, to foster research and development and facilitate commercialization within the CGT area, numerous initiatives have been undertaken by both the Indian government and private enterprises:

1. The Indian government has embarked on a series of initiatives aimed at enhancing the regulatory framework to align with global standards. Beginning with the formulation of the Guidelines for Stem Cell Research and Therapy in 2007, which were subsequently revised and released as the National Guidelines for Stem Cell Research (NGSCR-2013), efforts have been made to incorporate recent advancements and harmonize regulations. Further revisions culminated in the release of The National Guidelines for Stem Cell Research, 2017. In 2019, guidelines were issued to establish a regulatory framework for gene therapy, emphasizing long-term follow-up for clinical trials and post-commercialization monitoring.
2. The proposal for the creation of an independent body, the Gene Therapy and Advisory and Evaluation Committee (GTAEC), underscores the government’s commitment to supervising emerging therapies, bolstering research centers’ efforts in this domain.
3. Government’s encouragement of increased clinical trials, with institutions like the Indian Institutes of Technology (IITs) playing a pivotal role, highlights its support for research and development. National funding agencies such as the Indian Council of Medical Research (ICMR), Department of Biotechnology (DBT), and Department of Science and Technology (DST) have played a crucial role in fostering basic and clinical research, leading to the establishment of state-of-the-art infrastructure across premier health research institutes and supporting industry initiatives. Monitoring mechanisms, including the National Apex Committee for Stem Cell Research and Therapy (NAC-SCRT) at the national level and the Institutional Committee of Stem Cell Research (IC-SCR) at the institutional level, ensure adherence to guidelines and effective oversight.
4. Numerous companies are conducting clinical trials to address the pressing need for affordable therapies. Compliance with NGSCR 2017 is mandatory for research involving human stem cells and derivatives, while startups and larger companies alike are driving innovation through collaborations within India and globally. Recent developments, such as Eyestem Research’s funding round and partnerships between Laurus Labs and academic institutions, underscore the burgeoning interest and investment in the field.
5. The establishment of Miltenyi Biotec’s office and plans for a Centre of Excellence for cell and gene therapy further exemplify the growing momentum in this sector.
6. India’s launch of the ‘Sickle Cell Anaemia Elimination Mission,’ aimed at eradicating the disease by 2047, demonstrates the nation’s rapid advancement and alignment with other developed countries in this arena.

The trajectory of research and innovation in the field of R&D can be discerned through the trends observed in patent portfolios over the past decade. In the realms of cell therapy and gene therapy, there has been a notable surge in patents related to various diseases since 2015. These encompass conditions such as polio, ocular disorders, hepatic diseases, T and B-cell lymphoma, hematoglobinopathies, neurological disorders, and different types of cancers including liver and breast cancer. The vectors employed in these therapies range from AAV, recombinant, and expression vectors to Lentivirus vectors. Beginning in 2020, there has been a noticeable increase in patents related to COVID, gene editing, and the CRISPR-DCA13 system. These patents span a wide array of diseases including P-thalassemia, Duchenne muscular dystrophy, cystic fibrosis, retinopathies, hemophilia, Usher syndrome, Hurler syndrome, spinal muscular atrophy, cystinosis, and infantile neurosis. This evolution in patent trends reflects the dynamic landscape of R&D and underscores the ongoing quest for innovative solutions to address diverse medical challenges.

Hence, numerous leading entities are ascending the ranks and significantly influencing the trajectory of the cell and gene therapy landscape in India. Some of these are:

1. Intas Pharmaceuticals: The establishment of the Centre of Cell & Gene Therapy (CCGT) within Intas underscores their commitment of discovering, developing, and providing cost-effective treatment options, with a focus on developing innovative gene and cell-based therapeutics for various conditions including blood-related disorders, blindness, muscular dystrophies, and cancers. Equipped with cutting-edge technologies and state-of-the-art infrastructure, CCGT is at the forefront of transformative research in the field. With a strategic emphasis on drug discovery and process development, CCGT is actively involved in pioneering AAV-based gene therapy and lentivirus-based cell therapy products. Intas Pharmaceuticals, through its collaboration with CCGT, is advancing a pipeline comprising six AAV-based gene therapy and three LV-based cell therapy products. Through these efforts, Intas is dedicated to delivering cost-effective and impactful solutions to address critical medical needs.
2. Reliance Lifesciences: Reliance Life Sciences’ Regenerative Medicine Group is spearheading the development of a diverse array of innovative cell therapies, ushering in a new era of Regenerative Medicine. This group is engaged in cord blood banking and the advancement of a broad spectrum of research-led autologous and allogeneic cell therapies. These cell-based therapies aim to address unmet patient needs across various medical domains, including hematopoietic disorders, hematopoietic malignancies, cardiac disorders, ophthalmic diseases, neural degeneration, spinal cord injury, large burns, metabolic disorders, non-healing diabetic and venous ulcers, and bone and cartilage disorders. Reliance Life Sciences has conducted extensive research and development in human adult stem cells, such as mesenchymal stem cells and hematopoietic stem cells, as well as live skin substitutes. Noteworthy achievements include establishing the safety and efficacy of certain cell therapies through clinical trials, such as autologous bone marrow-derived mesenchymal stem cells for cardiac and neurological disorders, ReliNethra®, an autologous composite limbal epithelial graft for treating Unilateral Limbal Stem Cell Deficiency, and ReliNethra® C, an autologous conjunctival epithelial graft for conjunctival didisorders.
3. IIT Kanpur: The collaboration with Laurus Labs and the licensing of gene therapy technologies for hereditary diseases by Reliance Lifesciences Pvt. Ltd. signify a their significant stride towards pioneering research in gene therapy.
4. Stempeutics: This Bangalore-based life science company is dedicated to developing and commercializing novel therapeutics centered around adult stem cells. Through a commitment to nurturing cutting-edge research and clinical applications, they are actively engaged in the development of innovative stem cell products. Their flagship product, Stempeucel®, represents a groundbreaking patented cell therapy platform. It has received approval from the Drug Controller General of India (DCGI) for commercial use in treating knee osteoarthritis and critical Limb Ischemia (CLI) within India. Notably, Stempeucel® holds the distinction of being the first stem cell product globally to receive approval for the CLI indication.
5. The “Accelerating the Application of Stem Cell Technology in Human Disease” (ASHD) program, initiated by the Institute of Biological Sciences, focuses on leveraging stem cell technology for research, diagnostics, and therapeutics. Supported jointly by the Department of Biotechnology (DBT) and the Pratiksha Trust, this initiative involves collaboration among top Indian institutes such as the National Centre for Biological Sciences (NCBS), Institute for Stem Cell and Regenerative Medicine (inStem), National Institute for Mental Health and Neurosciences (NIMHANS), and the Christian Medical College (CMC) with the Centre for Stem Cell Research (CSCR) at Vellore. Additionally, the ASHD program has partnered with the Centre for iPS Cell Research and Application (CiRA) at Kyoto University, Japan, led by Prof. Shinya Yamanaka, a prominent figure in stem cell tetechnology.
6. Regrow Biosciences Pvt Ltd.: This company stands out as a pioneer in the field, actively dedicated to advancing the utilization of cell-based platforms across a wide spectrum of disease indications. Their focus extends to musculoskeletal disorders, urology, oncology, and soft tissue injuries, demonstrating a commitment to addressing diverse medical challenges through innovative approaches.
7. Helex Inc.: It specializes in cell and tissue-specific editing for safer in vivo gene editing, addressing a significant challenge in the field. Through their Double Lock Safety system, they prevent editing in unwanted tissues by employing tissue-specific vector modifications (first lock) in combination with Hele-GUIDE™ tissue-specific gRNAs (second lock), enhancing safety measures. Hele-GUIDE™ represents a proprietary technology that enables the customization of guide RNAs to specific tissues, thereby preventing editing regardless of transduction into unwanted tissues.

Indeed, the next few decades are poised to be transformative in the cell and gene therapy (CGT) space. With ongoing advancements in research and technology, the potential for groundbreaking therapies to emerge is substantial. It will be fascinating to observe which products successfully navigate the rigorous clinical and regulatory pathways to reach the market next and the timelines for their arrival. The evolving landscape of CGT holds immense promise for revolutionizing medical treatment paradigms and improving patient outcomes.