The Indian life sciences industry recently witnessed a quiet but significant milestone. On March 26, 2009 the office of the Drugs Controller General of India (DCGI) gave the go ahead for conducting clinical trials in India for a novel stem cell based therapy for treating cardiovascular diseases and limb ischemia. The approval was granted to Stempeutics, a Bangalore-based company that is developing therapies using adult mesenchymal stem cells.
The approval process took 18 months. A multidisciplinary team of eminent scientists, clinicians and officials from the DCGI and Indian Council for Medical Research (ICMR) after careful consideration of the ethical and scientific aspects approved the protocol proposed by Stempeutics. With this India became one of the first countries in the world to give approval to clinical trials for a stem cell based therapy that will be available off-the-shelf.
ADULT STEM CELLS
Adult stem cells are undifferentiated cells present in very small numbers, among differentiated cells of a tissue or an organ. They are capable of self-renewal and differentiation into the cell type of the tissue of origin, but remain undifferentiated unless activated by a disease or tissue injury. Thus, they are the repair machinery of the tissue. They are found in bone marrow, peripheral blood, blood vessels, skeletal muscle, skin and liver. Stem cells from the bone marrow are of two types - mesenchymal stem cells (MSCs) and haematopoietic stem cells (HSCs). MSCs are capable of differentiating into bone, cartilage, adipose, fibrous and connective tissues, while HSCs are capable of producing different types of blood cells.
CURRENT TREATMENT OFFERINGS
Therapy from adult stem cells can be divided into two types - autologous and allogeneic. Autologous is where a patient receives stem cells that have been isolated and processed from his/her own blood. On the other hand, allogeneic is where a patient receives stem cells that have been isolated and processed from a donor. Both these techniques have their advantages and disadvantages.
Autologous therapies are easier to commercialise, do not require any regulatory approval, as they qualify as a surgical procedure and the risk of immune rejection is also reduced as the patient's own blood is used to derive the stem cells. But they are relatively difficult to administer as an elaborate surgical procedure is required and consequently the cost of therapy is high.
Whereas allogeneic therapies are easy to administer, can be infused at the site and are less invasive, keeping the cost of therapy low and easier to access. But allogeneic therapies require regulatory approval as foreign origin cells are being injected into the human body and there is the risk of immune rejection.
Potential of allogeneic therapies Stem cells, because they can differentiate into different cells types, have great therapeutic potential in the treatment of diseases that have few treatment options such as Parkinson's disease, Alzheimer's disease, cancer, genetic disorders and spinal cord injuries. The potential application of stem cell therapies is wide and covers a large spectrum of possible indications from simple transplantation of stem cells to tissue engineering.
Some of the diseases that may be treatable with stem cell therapies include:
● Type I diabetes
● Cardiac ischemia
● Myocardial infarction
● Multiple sclerosis
● Lupus
● Rheumatoid arthritis
● Stroke
● Critical limb ischemia
● Heart failure
● Crohn's disease
● Diabetic wound care
● Asthma and chronic obstructive pulmonary disease (COPD)
● Bone Repair
● Graft Vs. host disease (GVHD)
● Liver disease
● Breast reconstruction
● Age-related macular degeneration
● Liver cirrhosis
● Parkinson's disease
● Alzheimer's disease
● Cerebral stroke
● Multiple sclerosis
● Meniscal injury
● Tendon injury
Although the main diseases that are being pursued for stem cell therapies have a large patient population, it is expected that only a small percentage of these patients will actually utilise these therapies. The main reason for this is that stem cell based therapies are expected to be used after other conventional therapies have been tried and have failed. As a second line therapy, physicians are likely to reserve these products for patients with few other treatment options. Contributing to the expectation of stem cells as a second line therapy is the expected high cost of these products and the lack of studies comparing stem cell therapies with conventional medication.
Market potential of allogeneic stem cells
According to a Frost & Sullivan study, the total addressable market for off-the-shelf adult mesenchymal stem cell therapies in India is approximately INR 2,206 crore. The therapeutic focus in India is on diabetology, leg ischemia, meniscus injuries / tendon injuries, liver cirrhosis, cardiomyopathy, Parkinson's disease, end stage renal disease (ESRD) and spinal cord injury.
Treatment of diabetes using stem cells has potential in Type 1 diabetes and diabetic foot. Type 1 diabetic treatment is expected to take up the maximum demand, with an INR 1,034 crore market.
Leg ischemia is a disease caused by severe obstruction of the arteries that result in a significant decrease in blood flow to the legs. Leg ischemia is a serious disease that often results in severe leg pain and the formation of the ulcers. Currently, there are approved medications to treat leg ischemia. The expected demand for stem cell therapy to treat Leg ischemia is about INR 326 crore.
Meniscal injury is another area where adult stem cell therapies have a lot of potential. This injury that occurs in the avascular zones has very limited potential to heal because of a poor blood supply. Although there have been many attempts to promote the healing potential of the torn meniscus, no established treatments have achieved sufficient meniscal healing. The expected demand for stem cell therapy to treat meniscal injuries is about INR 336 crore.
End Stage Renal Disease (ESRD) is a nephrological condition that affects a large number of patients. Only 7-10 per cent of ESRD patients receive either a cadaver / live kidney transplant every year. Though the percentage of patients progressing to advanced stage of renal failure is the same for acute renal failure (ARF) and chronic renal failure (CRF), nephrologists are of the opinion that early intervention of stem cell therapy at ARF stage will be comparatively beneficial. The approximate annual expected market demand for three Nephrology conditions across Tier 1 Indian hospitals is INR 127 crore.
In the case of neurological disorders, Parkinson's and Alzheimer's disease are two neurological conditions most lacking in treatment modalities. Deterioration in quality of life is comparatively less severe in cerebral strokes. In cases of multiple sclerosis, despite effective medication methods, quality of life is appalling. The approximate annual expected market demand for neurological conditions across Tier 1 Indian hospitals for the above four conditions is INR 145 crore. In addition to these conditions, spinal cord injury (SCI), optic nerve injury (ONI) and brain damage (BD) are some of the critical areas where stem cell therapy has tremendous potential.
One of the most promising areas for the use of stem cells therapy is in the field of cardiology. One of the reasons that heart disease kills people is the inability of the heart to heal itself after an attack. Despite advances in surgical procedures, mechanical assistance devices, drug therapy and organ transplantation, more than half of patients with congestive heart failure die within five years of initial diagnosis. Researchers are now exploring ways to save these lives by replacing dead or impaired cells so that the weakened heart muscle can regain its pumping power. Heart disease is one of the biggest killers in the world. According to the WHO India is expected to account for almost 60 per cent of the heart patients in the world. The expected market for stem cell therapy to treat the various ailments in the cardio vascular disease segment is expected to be INR 243 crore.
Allogeneic stem cell product development
Currently, adult stem cells are more difficult than embryonic stem cells to grow in cell culture. However, new research into adult stem cells has improved the cell culture process. In addition, after a few doublings adult stem cells can lose their potency and may even stop dividing. Furthermore, because adult stem cells are less plastic than embryonic stem cells, they can differentiate into only limited number of cells. This implies that the therapeutic potential for adult stem cells is more limited than for embryonic stem cells.
Adult stem cells are less controversial than the embryonic stem cells. The access to adult stem cells is also not as much as an issue compared to embryonic stem cells. These are some of the reasons that globally adult stem cells are preferred for therapeutic purposes. The global stem cell therapy market is currently dominated by adult stem cells companies, which hold 58 per cent of the market.
When it comes to developing therapies using adult stem cells, US tops the chart with about 25 companies engaged in it. Also there are companies developing therapies using bone marrow derived stem cells. The US also leads the world in the number of patents: 109 patents in Adult Mesenchymal Stem Cells. In India, other than Bangalore-based Stempeutics, Reliance Life Science is developing stem cell related therapies. Additionally, various hospitals such as All India Institute of Medical Sciences (AIIMS), Apollo Hospital, Escorts Hospital, Narayana Hrudayalaya etc are using autologous stem cells to treat various conditions.
Emerging business models
There are four main emerging business models in connection with the development of therapeutic stem cells. The first two pertain to whether or not a company is developing therapies that contain embryonic or adult stem cells. The other two models involve the development of mass-produced pre-made stem cell products or customised stem cell products that are made specifically for a patient. Biotechnology companies that are developing stem cell therapies are concentrating their efforts on the development of adult stem cell products or embryonic stem cell products.
Some companies are opting to follow the business model used for other biologics like monoclonal antibodies by making mass-produced 'off-the shelf' products. Other companies are focusing on the production of custom made stem cell products (both autologous and allogeneic) that are produced specifically for the patient. Both approaches to stem cell therapy offer great therapeutic potential. However, it is expected that there will be a substantial price difference between these two types of products with the mass-produced stem cell products costing significantly less than the custom made stem cell products.
The potential use of adult stem cells is only just starting to be realised. The approval of the clinical trials to treat acute myocardial infraction and leg ischemia by the Indian regulatory authorities is a step in the right direction and shows that Indian regulators are in touch with the latest advances in the world and that Indian life science companies are slowly starting to compete with global companies in cutting edge therapies. India with its huge burden of diabetes and heart disease is a market that offers a lot of potential if companies are able to deliver their products at an affordable price.
(The author is an industry analyst with Healthcare Practice, Frost & Sullivan. For feedback/enquiries contact remi.chaterjee@frost.com)