March 24 is World TB day. It commemorates the discovery of Tuberculosis (TB) bacillus in 1883 by Dr Robert Koch as the cause of tuberculosis . Koch’s discovery paved the way for diagnosis , treatment and vaccine development to cure and eradicate the disease.
More than a century later, TB still remains a global problem, causing a death somewhere in the world every 20 seconds. India has the largest incidence of TB in the world . Yet, TB is a curable disease. There are many reasons for high mortality.
Timely and accurate diagnosis is still a challenge. The treatment duration and side effects of the drugs make compliance a challenge. The current therapy involves a four-drug regimen – Rifampicin, Isoniazid, Pyrazinamide and Ethambutol – administered over a period of 6-9 months under the direct observation of the doctor called directlyobserved short-duration therapy (DOTS).
It is a WHO-recommended process for delivering TB therapy. But there is a need now to introduce improved diagnostics, new drugs and a shortened regimen. Also, drugs currently in use under DOTS were discovered in the middle of the last century.
No new drugs that provide significant advantage over the long-duration combination therapy have yet been introduced into the regimen. This is a combined failure of many factors, including the lack of translational science to challenge the current paradigm in therapy, poor response from innovative drugmakers, failure of regulators to promote speedy introduction of new drugs into the regimen and, lastly, a lack of advocacy from the patient groups demanding better drugs.
The primary reason for lack of innovation lies in the market dynamics. Conventional patent-based drug development model fails to ensure return on investment in research in the absence of market forces.
The global market for TB is estimated at $300-400 million. The estimated cost of discovery and development of drugs in the pharma sector is over $1 billion. Because of this asymmetry, the industry has little incentive to develop new drugs.
Therefore, higher public investment is an imperative, particularly in clinical development. The Global Alliance for Tuberculosis has been set up to address some of these issues. A few pharmaceutical enterprises have found innovative models to invest in discovery and identification of promising clinical candidates.
But these bodies have been dependent on public funding agencies like the National Institute of Health, US, and its sister organisations for derisking and supporting clinical development. This dependence on public funding is prompted by the multifold challenges in the clinical development process for registering new molecules for TB treatment like the need to underwrite the financial risk due to unattractive returns; assessment of challenges in regulation and determining how to make drugs accessible to patients.
The Council of Scientific and Industrial Research (CSIR) has facilitated discovery of new drugs for TB in a public-private partnership (PPP) model as evinced in the development of Risorine, an adjunct therapy for TB, by Cadila Pharma.