A biomarker or biological marker, is defined as a characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes or pharmacologic responses to a therapeutic intervention. Researchers are very well aware about the potential these biomarkers have in the field of diagnostics and new drug development. Currently, research efforts are focusing particularly on the discovery of biomarkers that are unique to a particular disease condition.
In India, though biomarkers have been recognized for decades and have been immensely successful in detection of several diseases, emergence of biomarkers as a significant and widely used tool in the arena of clinical research and drug discovery is relatively recent. With the growth in clinical research and the flourishing healthcare sector, the scope of using biomarkers is also increasing.
Many Indian CROs and biopharmaceutical companies have now started using biomarkers for the research, treatment and developmental work in therapeutic areas. The use of biomarkers have not just helped the development of pharmaceuticals but also improved the process of diagnosis and hence treatment of individual health conditions. Its added advantages include the cost effectiveness and reduced time of drug discovery.
Currently, biomarkers are playing an active role in four main areas: discovery, pre-clinical, clinical and diagnostics, which include the following:
Identification of disease at very initial stage: Biomarkers are emerging as important molecules whose detection can help predict the presence of diseases such as cancer, Alzheimer's disease and Parkinson's disease at an early phase. In the future, they will be a promising diagnostic tool for clinicians for the early detection of these diseases.
Identifying potential drug targets: A study of biomarkers would help pharmaceutical companies in validating drug targets, as they make researchers understand the disease process at the protein expression level. At present, researchers use advanced techniques like proteomics to find these proteins (biomarkers) specific to various disorders, which may offer a potential target for drug treatment.
Estimating the efficacy of drug: Biomarkers can help physicians monitor the response of medication administered to patients suffering from serious ailments and judge the efficacy of a particular drug regimen in terms of cure rate. Biomarkers play a major role in reducing trial duration by predicting drug efficacy in animal models and human trials by acting as surrogate primary endpoints.
Personalized medicine: Biomarkers would help physicians prescribe the right medication to the right patient. This would reduce the side effects as patients would be prescribed a drug after determining the particular pathway that is playing an active role in the progression of disease in the patient in concern. This is because the same disease can progress through different pathways in different patients.
Accelerating clinical trials
It is revealed that approximately 90 percent of compounds fail during clinical development. Over 60 per cent of those failures are due to absorption, distribution, metabolism, excretion (ADME) problems, as well as toxicology. Biomarkers are often instrumental in eliciting disease targets and pathways. Biomarker helps in reducing detection threshold of low abundant protein which acts as barrier in disease progression and host response.
Biomarkers can also act as pharmacodynamic indicators of drug activity, response and toxicity for use in clinical development. They help researchers in validating mechanisms of drug action by predicting the progression of a specific disease or disorder. They can be used to evaluate drug therapies in clinical trials, acting as 'surrogate endpoints' during clinical trials where ultimately the condition would lead to the patient’s death if not treated effectively.
Biomarkers for treatment
Biomarkers are helpful in detecting the disease at its earliest stage and enable to seek vital information as every disease progresses with the progression or expression of the unique biomarker. The early diagnosis also makes the conditions more manageable and hence the treatment becomes easier with favourable results. This makes physicians confident to use biomarkers to monitor and treat several diseases.
Biomarkers could also prove invaluable in determining the efficacy of drugs for neurological diseases such as Alzheimer's where currently the only way to conclusive tell whether a patient has the disease is to open up the brain after death and look for the build-up of amyloid plaques.
Additionally they can be used to monitor a patient’s response to a drug to minimise the likelihood of them suffering an adverse event (AE).
Many of diagnostic biomarkers discovered in a number of diseases are actually low-molecular weight processed products. For instance, low-molecular weight proteins such as defensins (recently shown to be important for inhibition of viral replication) are a novel biological function in addition to their known anti-microbial function.
Now-a- days, cancer is one area where biomarkers are extensively used. Biomarker test gives information regarding activities of disease, particularly in cancer.
These biomarker tests are carried out in serum. Biomarkers are also very helpful in the development of new drugs for cancer treatment. Specific biomarkers are used to see the response to the new drug for cancer. Due to its early diagnostic quality, biomarkers are used in many of the rapid diagnostic kits. Many genetic disorders, cardiac related problems are diagnosed through biomarkers. Carcinoma of ovary, testicular tumour, colon cancer, carcinoma of pancreases can be diagnosed with the use of biomarkers like Beta SCG, CA-125, CEA, CA19.9 and alfa feto protein.
Cost -effectiveness
Apart from being helpful in clinical research, drug discovery and treatment of diseases, biomarkers also have significance in terms of cost. The early identification and treatment of disease not just leads to best outcome but also less long term expense. Biomarkers are helpful in making efficacious and cost saving decisions. With the early prediction of disease and the effects of drug, it is easier to terminate drug entities more quickly during clinical trials. Biomarkers help in identifying certain patient populations that are more likely to respond to the drug therapy or to avoid specific adverse events. This serves immensely in terms of time and money. With biomarkers targeting at the detection of individual states of diseases, there is a shift towards personalised medicine where a particular patient receives a treatment based on his genetic and medical profile. This shift has proved to be a boon for pharmacos and CROs who are desperate to expedite the drug discovery process while decreasing the expense.
Personalised medicine
Enabling personalized medicine through biomarkers presents an exciting opportunity for helping the pharmaceutical industry and perhaps changing the current drug development paradigm. For example, Herceptin and Gleevec are the drugs that are only prescribed after patients undergo a test to confirm that the drugs will benefit them. Here, the concern is not to curb the utilization, but to provide limited exposure to patients who will not benefit from and may be harmed by inappropriate therapies. The biomarker helps to rationalize therapy, rather than to restrict it.
Global market for biomarkers
The biomarker analysis market has excellent growth potential. The field is progressing so rapidly that new biomarkers are discovered each day. Still there is a huge gap between the time that a biomarker is discovered in the laboratory and when it is actually commercialized, due to the various challenges faced in the biomarker validation and assay development.
The biomarker market mainly consists of tier 2 companies and start-ups. There are some contract research organisations (CROs) that double up as biomarker analysis companies in that they provide these services to biopharma clients. There are also companies that act as CROs but also have a division that carries out biomarker research in parallel. Therefore, the biomarker market is a multivariate one that consists of all types of companies.
The biomarker market is in the early growth phase and is expected to continue in this phase for few more years, during which many new biomarker panels are expected to be approved by the regulatory authorities for mainstream testing during pre-clinical and clinical drug development. By 2015, biomarker analysis market is expected to complete its late growth stage and attain maturity.
Though the US is the leader in the biomarker market, some of the world class biomarker companies are found in Europe. The western European region is not far behind United States in terms of market size and growth rate. Asian countries like Japan are almost on par with the Europe and South Korea is also testing the frontiers of biomarker research and development.
Visiongain, a London-based business information provider, predicts that the global biomarkers market will be worth $19.86bn in 2015. The market generated $14.18 billion in 2010, according to Biomarkers: Technological and Commercial Outlook 2011-2021, published in June 2011. The global market for biomarkers is forecast to reach $34 billion by the year 2017.
What the future holds?
While organisations are gearing up to get global trials and infrastructure in place to conduct trials to identify and use biomarkers for diagnosis and management of diseases, researchers are now examining ways to put powerful laboratory technologies to work for clinical applications by developing more precise and accurate measures of disease. These tools, which were developed to assess cellular and molecular processes or to study animal models of disease, are now being refined for use in human patients and may play a key role in speeding assessment of new therapies. Examples of these tools include high resolution imaging modalities such as functional magnetic resonance (fMRI) and positron emission tomography (PET), cDNA microarray, two-dimensional gel protein electrophoresis and tetramer assays to classify lymphocyte populations. Novel applications of these discovery tools are enabling researchers to identify biological markers that describe and predict the status of disease or conditions. Blood pressure, cholesterol, certain tumour markers such as prostate-specific antigen and brain plaques that occur in multiple sclerosis include some of the classical biomarkers that serve this purpose.
Growth is also being spurred by increasing support from government agencies worldwide, including the USFDA in biomarker research. This in turn is a result of increasing failures in drug development, primarily in areas such as oncology. Major area of biomarker adoption in drug development is in the form of surrogate biomarkers that act as substitutes for clinical endpoints in drug development. Biomarker use in selection of drugs is expected to increase in the coming years. Related techniques are expected to find increasing use across the drug development spectrum, ranging from preclinical studies to diagnostic therapies in certain patient sub populations. Although biomarker identification and related techniques are still undergoing development, they show great promise in delivering substantial benefits to health management in the future.
The author is Process Excellence Group, Tata Consultancy Services, UP