Future of Drug Discovery

The cost of drug discovery has ballooned to $1.3 billion ^[1]. The number of approvals of new drugs has significantly reduced. Nearly 43% of drug candidates fail due to efficacy problems, 33% due to safety concerns, and 11% due to pharmacokinetic issues during development ^[2]. Further, approved and marketed drugs are being withdrawn due to concerns regarding long-term safety, with 94% of such withdrawals due to toxicity ^[2].

Regulatory agencies are also seeking longer clinical studies in larger populations due to increased safety concerns. This has escalated the cost of drug discovery, driving the focus of Research & Development (R&D) primarily on "billion dollar" indications. Recovery of drug discovery investments today is only from highly priced and insurance reimbursed regulated markets such as USA, EU and Japan, which contribute as much as 80% of the market value ^[3]. Rest of the world (ROW) with 85% of the population represents only 20% of the market. This market bias defeats equitable and inclusive drug discovery. Indications like Malaria, Dengue and Tuberculosis are neglected. A disruptive innovation is required to change the existing drug discovery paradigm for addressing this inequity.

The current discovery model is primarily responsible for this high cost, time and risk of drug development. The target-based, in-vitro driven approach is unable to predict the activity of a drug candidate in living beings at an early stage of development. Several million dollars are spent on preclinical development before wet pharmacology studies are undertaken. Tens of thousands of molecules undergo logarithmic attrition during prospective stages of development. Essentially, the current model does not provide risk-mitigated justification for the huge R&D investments. According to Dr. Bowman, "Less than 1% of developing drugs result in success, but the pursuit of many promising "failed" drugs can cost a company millions of dollars in R&D" ^[4].

Indus Biotech’s unique discovery paradigm creates ways to mitigate late stage failure of drugs due to safety and efficacy reasons, while reducing the net cost of discovery. Indus Biotech uses a disease-based model, prospecting for molecules from food chain raw materials, with established safety and physiological activity and used for human consumption over millennia. This unique approach mitigates the uncertainty of a future safety failure at an early stage of development.

Indus Biotech’s disease-based discovery model starts with in-vivo screening (wet pharmacology) of molecules for assessing the safety and efficacy in living beings. Researchers across the world have started realizing the importance of an in-vivo driven discovery model ^[4]. Early in-vivo screening helps in assessing the multiple target activity of the drug molecule as well as knowledge on potential side effects. This approach has also proven that development cost can be reduced without compromising the science of drug discovery.

Another advantage of Indus Biotech’s model is the possibility of early proof-of-concept studies to understand human safety and efficacy response, thus establishing confidence in the potential of a drug molecule before incurring the high cost of regulated clinical trials. Since the molecules are derived from food chain raw materials and not chemically synthesized, preclinical safety profile and efficacy results create convincing evidence to conduct a human proof-of-concept study in accordance with the ethical and legal requirements of drug development.

Last but not least, the United States Food and Drug Administration has established new guidelines for Botanical drugs that allow Indus Biotech to work on drug substances with assured therapeutic consistency. This regulation offers significant cost reduction in drug manufacture by permitting poly-molecular assays with benign impurity profile, which is generally the case when starting from food chain raw material. In contrast, the synthesis of a New Chemical Entity (NCE) requires sophisticated and costly manufacturing process steps for limiting toxic impurities to significantly low levels.

The widespread use of botanical drugs will have other collateral benefits, such as a positive impact on the global issue of climate change. The additional cultivation of food chain raw materials for drug use will increase and sustain green cover, thus reducing carbon foot-prints and providing an opportunity to improve and sustain an agrarian economy. For a country like India with 60% of its population engaged in agriculture, the greater use of botanical drugs provides higher earning potential for marginal farmers. This obviates the need for migration to urban centres for employment, thereby reducing the burden on already overpopulated, polluted and resource limited cities.

Indus Biotech’s innovation redefines the future of drug discovery by dramatically reducing the drug development cost and time to market. By making the choice of a disease and using food chain raw materials as a starting point of drug discovery, this model mitigates the burden of uncertainties in drug development, while capturing the essentials of science, safety and efficacy of the current NCE paradigm.

In conclusion, by reducing risk, time and cost to market, Indus Biotech’s discovery model addresses the need for investments in R&D of neglected diseases. It also offers opportunity for pharmaceutical industry to expand into untapped ROW markets, which today exhibits growth rates as high as 14-15% per annum ^[3]. For the first time, pharmaceutical companies can look beyond blockbuster indications with exciting growth opportunity.

References:
[1] DiMasi et al. (2007), Managerial and Decision Economics, vol. 28 (4-5), pp. 469-79.
[2] Schuster et al. (2005), Current Pharmaceutical Design, vol. 11, pp. 3545-3559.
[3] World Pharmaceutical Frontiers, March 2009, pp. 18-21.
[4] Bowman et al. (2010), ACS Chemical Biology, vol. 5 (2), pp. 159-161.