What was thought to be the diseases of the European and American ancestry, neurodegenerative diseases are now becoming prevalent amongst Asian population as well. This has got the attention of drug developers in the Asia Pacific and they have started exploring this $30 billion potential market

Singapore, Feb 25, 2010: There are over 40 identified neurodegenerative diseases, however, multiple sclerosis, Alzheimer’s and Parkinson’s diseases are the three major concerns for researchers. The increasing patient population and the marginal effectiveness of the present drugs make these diseases a cause of concern as well as an opportunity for drug developers.

In neurodegenerative disease segment, multiple sclerosis drugs bring the major share of income for the drug makers globally. According to industry trackers, this is because of the fact that majority of the drugs used to treat multiple sclerosis are biologics. The huge investment required in setting up a generic manufacturing unit and the time taken for regulatory approval prompts the companies to opt for biologics.

According to a market research report by Cutting Edge Information, the sales of neurodegenerative drugs in 2009 totaled $18.5 bn and are expected to increase 62 percent to $29.7 bn by 2012. The majority of this growth is projected to be in multiple sclerosis, which will increase from $12.6 bn to $20 bn in 2012. The revenue for Alzheimer’s drugs will increase from $5 bn to $8 bn in 2012, and the revenue for Parkinson’s drugs will increase 50 percent from $1 bn to $1.5 bn in 2012.

Japanese drug maker, Eisai’s blockbuster drug Aricept is indicated for the symptomatic treatment of Alzheimer’s dementia and vascular dementia. Aricept contributes nearly $3.2 bn to the total revenue of the company, globally. The drug was first launched in 1997 in the US in co-promotion with Pfizer. Aricept is the most widely prescribed Alzheimer’s treatment in the world and is approved in more than 90 countries.

The drug was launched in India as Aricep in 2005 and has become brand leader in dementia market with 21.4 percent market share. Eisai recently expanded its operations in India with a drug plant in South Indian coastal city of Vishakhapatnam. According to Mr Deepak Naik, Managing Director of Eisai Pharmaceuticals (India), the new facility will be used, initially, to manufacture Aricep and another blockbuster drug Myonal.

Australia-based Prana Biotechnology was established to commercialize research in Alzheimer’s disease and other major age-related neurodegenerative disorders. The company’s lead product, PBT2, has already completed a phase IIa study in early Alzheimer’s disease patients and has demonstrated safety and tolerability. In addition, PBT2 showed improvement in executive function, an important aspect of cognitive performance, and reduced the levels of Abeta in the spinal fluid of patients. Abeta is a key protein associated with Alzheimer’s disease. In August 2009, the company received a US patent for PBT2. Prana has also secured patents in Russia, Singapore, South Africa, and New Zealand and has a Notice of Acceptance in Australia.

In December 2009, India-based Suven Life Sciences received Canadian patents for two of its new chemical entities (NCEs) indicated for the treatment of neurodegenerative disorders including attention deficient hyperactivity disorder (ADHD), Huntington’s disease, Parkinson’s disease and schizophrenia. The company has six internally-discovered therapeutic drug candidates currently in pre-clinical stage of development, targeting conditions such as ADHD, dementia, depression, Huntington’s disease.

New Zealand-based Neuren Pharmaceutical focuses on both acute and chronic neurodegenerative diseases. The company’s pipeline predominantly derives from the naturally occurring neuropeptide IGF-1(1-3). Neuren’s lead clinical candidate is a synthetic peptidomimetic of IGF-1 (1-3) and its lead preclinical candidate is a synthetic analogue of one of its active metabolites. The second clinical-stage compound is a novel pryllidone derivative that increases neurotransmitter levels and calcium channel activity in the cortex.

NCRM’s work focuses on isolating bone marrow stem cells, increasing the number of cells in the lab, and injecting them back in the affected area, thereby the injected stem cells would repair the damaged cells, replace the lost cells, rejuvenate the existing cells by secreting relevant growth factors and regenerate new cells either directly or indirectly by increasing the blood supply to the affected area. Thus, the regenerated cells will take over the function of the lost/degenerated cells.

Mr BN Manohar, President of Stempeutics Research, a stem cell company with operations in India and Malaysia, says, “Researchers working on Parkinson’s disease have pioneered the use of cell-based therapies in the central nervous system. Cell-based therapies for Parkinson’s disease were originally envisioned as a way to replace the dopaminergic nigral neurons lost with the disease.”

Living Cell Technologies, a cell-based therapeutics maker with operations in New Zealand and Australia, is developing a cell product, NTCell, to treat neurodenerative conditions. In January 2010, the company has received a European patent for the use of this product for the treatment of Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, Huntington’s disease and stroke. NTCells are porcine choroid plexus cells encapsulated in a seaweed-derived gel. According to the company, NTCell is well tolerated in pre-clinical studies in primates with no evidence of adverse side effects.

Trends and opportunities
Drug makers are increasing their focus on the development of drugs that target multiple components of both well-characterized and newly discovered pathways rather than a single receptor, says Mr Larry Glass, CEO of Neuren Pharmaceuticals. The drugs that mimic the activity are derived from naturally occurring molecules and that stimulate or enhance neurogenesis are also becoming the areas of interest.

According to Mr Glass, Neuren’s drug, IGF-1(1-3) analogues, predominantly achieve neuro-protection by targeting glial cell function rather than purely neuronal mechanisms. Also, the IGF-1 (1-3) analogues target both inflammatory, apoptotic and necrotic processes simultaneously rather than just one component of the neurodegenerative cascade. Neuren’s another drug, Motiva’s effects on neurotransmitters are predominantly postsynaptic rather than pre-synaptic, which is believed to provide more targeted action and a better safety profile.

The trend in cell-based therapies is to replace the degenerated cells with appropriate cells, says Dr Abraham of NCRM. However, the group or subset of cells of bone marrow to be used is an area of intense discussions. Dr Abraham is of the opinion that even though the drug discovery based solutions are under way it would still be inferior to a cell replacement therapy as the cells are multi-functional and answers to the environment in all possible ways as long the cells are from the right source and is not rejected by the patient’s body (i.e., autologous).

Commenting on the opportunities for drug makers in this field, Dr Glass says, “There is growing evidence that neurodegeneration plays a role in a wider range of diseases than we had previously thought. Depression, for example, is now thought to be strongly associated with neurodegeneration, not only neurotransmitter regulation. As the number of indications associated with neurodegeneration grows, the size of the market increases dramatically. If we include psychiatric indications and epilepsy, it is potentially the largest overall market and probably be the one with best growth potential.”

Drug development for neurodegenerative diseases are gaining prominence after several years of negligence. Now with the active participation of Asian drug makers, we can expect the trend to pick up in the near future.