Monday, March 9, 2009

Emerging Drug Discovery Technologies - A Summary


The drug discovery process has changed significantly since the 1950s when drugs were discovered by rather a chance or random process: known compounds were screened or any molecules to hand were randomly tested, to a large part in in vivo models. Now, with the advent of molecular biology, coupled with advances in screening and synthetic chemistry technologies, a combination of both random screening and knowledge around the receptor is used for drug discovery.

An important consequence of today’s approach to drug discovery is that more lead molecules are being discovered for diverse targets, giving the medicinal chemist more scope to find a candidate molecule. However, the probability of success of launching a candidate molecule onto the market remains largely unchanged at around 8%, and the perception is that the time to market has not reduced as might have been expected with greater automation.

Numerous problem areas remain: current methodologies for compound synthesis, storage, and retrieval are inefficient and inadequate; better information is required to improve target selection and validation; more predictive screens are essential; greater emphasis must be placed on acquiring good ADMET data earlier in the discovery process; and novel screening methodologies are needed to dramatically increase throughputs and reduce reagent consumption.

Innovative technologies that generate high-value information in a condensed time frame, minimize the guesswork involved in target, lead and drug candidate selection, and minimize the effects or compromises inherent in drug discovery will lead to significant improvements in productivity across the spectrum of drug discovery operations. Three technologies that are predicted to do this are: lab-on-achip/microfluidics, nanotechnology and RNA interference (RNAi).
  • Lab-on-a-chip/microfluidics
A lab-on-a-chip (LOC) device is a microscale laboratory on a credit card sized glass or plastic chip with a network of microchannels, electrodes, sensors and electronic circuits. These LOCs can duplicate the specialized functions as performed by their room-sized counterparts, such as clinical diagnoses, PCR and electrophoretic separation.

Generally, a LOC device must perform a number of microfluidic functions: pumping, mixing, thermal cycling/incubating, dispensing, and separating. Precise manipulation of these microfluidic processes is the key to the operation and performance of LOCs.

The advantages of LOCs include significant reduction in the amounts of samples and reagents, very short reaction and analysis time, high throughput, portability and reproducibility.

Recent developments in LOCs have enabled the technology to move from the laboratory into the commercial world. Some of the major factors driving the growth and expansion of the LOC device market include: high throughput screening, increased automation, reduction in sample requirement, reduced exposure to hazardous materials, and the increased rate at which potential drug targets are screened.

In 2004, the world LOC/microfluidics markets generated an estimated $215.3m. The market is forecast to grow at a compound annual growth rate (CAGR) 2004 - 2012, of 27.8%, reaching $1530.4m in 2012. The market predominantly comprises of start-up companies, a few of which have managed to go public. The top five vendors (Caliper, Cepheid, Agilent, Combimatrix and Nanogen) accounted for approximately 48% of the market in 2004.
  • Nanotechnology
Nanotechnology is an enabling technology that deals with nanometer (10-9 meter) sized objects. Nanotechnology can enhance the drug discovery process, through miniaturization, automation, speed and reliability of assays.

Five nanotechnologies that will make a serious contribution to drug discovery are: atomic force microscopy, nano-mass spectroscopy, dip-pen nanolithography, nanoarray and nanoparticles.

Although, at an embryonic stage of development, nano-enabled drugs are already bringing clinical benefits to thousands of patients. Two such drugs are Abraxane for the treatment of metastatic breast cancer, and RenaZorb, which provides phosphate control in kidney dialysis patients.

There are a number of challenges that the industry must overcome in order for nanotechnology to reach its full commercial potential. These include addressing the issues of scalability, standardization, nanomaterial long-term stability, and the accuracy.

Some of the major factors driving the expansion of nano-enabled drug discovery include: identification of novel chemical structures, ability to manipulate and track cells on the nanoscale due to advances in microscopy, increased government funds earmarked for nanotechnology, significant and growing interest from the venture capital community and rapid proliferation of nanotechnology start-up companies.

The total world market for nanotechnology in drug discovery was estimated at $121.9m in 2004. The market is forecast to grow at a compound annual growth rate (CAGR) 2004-2012, of 29.3%, reaching $955m in 2012. The market predominantly comprises of start-ups. The top six vendors (QuantumDot Corp., Nanosphere, Nanoplex, C Sixty, BioForce NanoSciences and Fluidigm Corp.) accounted for approximately 57% of the market in 2004.
  • RNA interference
The landscape for gene silencing technologies has been significantly boosted by an emerging new technology called RNA interference (RNAi). RNAi has enormous potential in both target validation and therapeutics. RNAi technology involves targeting and interfering with messenger RNA (mRNA), a blueprint for building the protein being expressed. In this manner, if a protein is involved in the progression of a disease, RNAi can be used to stop it being expressed.

RNAi has great potential in that it provides a novel approach to drug discovery, validation and delivery. Industry and academic research work in this sector has been accelerated, as is evident from the number of scientific papers published on RNAi. Science named RNAi the technology of the year for 2002, and Fortune dubbed it biotech’s “next billion dollar breakthrough” in 2003.

The market for RNAi is relatively new and emerging. The technology has only been applicable to human systems since 2001. Rapid early growth has been seen in the market, which is being driven by the demand for novel drug discovery targets, an accelerated drug discovery process, and the robustness and effectiveness shown by RNAi in gene silencing.

In 2004, the total market revenue for RNAi technology was estimated at $1.1bn. The market is expected to grow at a compound annual growth rate (CAGR) 2004 - 2012, of 16.1%, to reach revenues of $3.7bn in 2012. Dharmacon is the largest provider of synthetic siRNA, accounting for 35% of the total RNAi market. Quiagen had a 16% RNAi market share in 2004, while Ambion accounted for approximately 9% of RNAi revenues. More companies are emerging in the RNAi market and companies such as Eurogenetics, MWG Biotech Inc., Imgenes Corp., Proligo, Intradigm Corp., Mirus Corp., Novagen and Imgenex Corp. together represent approximately 35% of the global RNAi market.


Post a Comment