Monday, February 15, 2016

Ending TB Epidemic – An Unreachable Milestone in Sustainable Development Goals?


Is it possible to end the epidemic of TB in the next 14 years as contemplated in the Sustainable Development Goals? Simple answer is a straight no!
The world is justifiably happy that the Millennium Development Goals (MDG)on TB of arresting and reversing the TB mortality trend has been achieved.  TB mortality has fallen 47% since 1990. This reduction by half is a significant achievement made possible by the enthusiastic implementation of DOTS and WHO and national governments deserve credit.
The Goal 3 of the Sustainable Development Goals (SDG) calls to end the epidemics of AIDS, tuberculosis, malaria and neglected tropical diseases by 2030 and combat hepatitis, water-borne diseases and other communicable diseases.
Achieving SDG targets will require management of the complex drug resistance (DR) problem in TB, particularly in high incidence countries like India.  
Why is it tough
The Global Tuberculosis Report 2015, reported 6 million cases of TB globally in 2014. It is estimated that around 3,00,000 had multi drug- resistant (MDR TB) while only 1,23,000 were detected. 1,90,000 people died of MDR TB. Globally, only 50% of MDR cases get successfully treated. More than half of the global DR TB cases are in India, China and Russian Federation.
As per WHO estimates, the cost per patient treated for drug-susceptible TB in 2014 ranged from US$ 100−500 in most countries. This is mostly met by public health system through DOTS, supported by Global Fund. The cost per patient treated for MDRTB was typically US$ 5000-10,000. The MDR TB costs almost 10 times and does impact national TB budgets significantly. If the large number of undetected MDR TB cases come up for treatment, even at the current costs there will be a significant burden on national TB control budgets. There are limitations on the reach of public facilities and many patients avail private care which is paid out of pocket. That is why there are serious concerns about the cost of new TB drugs.
Experts are unanimous that new drugs are needed to manage drug resistance.
Happily, there are new drugs are on the horizon. FDA has approved Janssen Pharmaceutical’s Bedaquiline (tradename Sirturo), based on Phase IIb results. Its Phase III trials are ongoing. Similarly, Otsuka Pharmaceutical’s Delamanid has also been approved by EMA based on Phase IIb results; its Phase III trials are still ongoing. TB Alliance is testing PA 824 in combination with other drugs. There are other candidates like, Sutezolid, a drug developed by Pfizer, now licensed to Sequella and AZD 5840 of Astra Zenecca.
Concerns
Yet, there are serious concerns of affordability and accessibility of the new drugs. This is due to the particular nature of TB. TB has earned the sobriquet ‘poor man’s disease’, and is prevalent in the less fortunate neighborhoods in the tropics.
The Cost of the New Drugs
Janssen has priced the Sirturo (Bedaquiline) at $ 30,000 in US for the course of treatment. Delamanid of Otsuka is marketed in EU under the tradename Deltyba in Europe and is priced at around US $ 30,000 (Delamanid costs £1,045.83 in UK and €1,500 in Germany, for a course).
The new standard of price seems to be USD 30,000. Janssen is offering the drug at a discounted price of $ 3000 in middle income countries and $ 900 in low income countries.
Even with the discounted price of $ 3000, if we add this price to the WHO’s lower estimate of the current cost of $ 5000, a course of MDR TB treatment with the addition of new drugs could cost around $ 8000. So the MDR TB regimen is likely to cost around Rs 5,00,000 or more in India.
This likely cost of MDR TB regimen would be beyond the means of a large number of TB patients. A comparison could be with the Income Tax payment threshold amount in India. India has a threshold limit of Rs 2,00,000 (~$3000) above which all are required to pay income tax and file returns. As per news reports, only 35 million tax payers (3.5 crore) have income above this limite and pay Income tax, which is just 3% of Indian population. Even in this bracket, the majority of the tax payers fall in the category of Rs 2,50,000 to Rs 5,00,000 bracket
As per the last census, the average household size in India is 4.8. Most of these households may have only one breadwinner. That adds to the financial strains of healthcare. The healthcare costs in India is largely borne by the patients with about 70% out of pocket expense (as compared to less than 30% in developed world). With most of the affected population being poor, the way the new drugs are being priced, MDR TB treatment will be priced out of reach of most of the affected population in the most affected countries.
Affordability is only one part. There is also a more serious concern of access to the new drugs.
Accessibility Issues
Both Bedaquiline and Sirturo are available only to patients in US and Europe, that too in limited numbers. It is reported that by March 2015, only around 1000 patients have received Bedaquiline. The results of the Phase III trials approved in 2013 is yet awaited; an indication of the length and complexity of TB clinical trials. Even if the trials are successful, Janssen has registered the drug only in 21 countries. Otsuka has moved for registration only in Europe, Japan and South Korea. WHO has issued guidelines on the use of Bedaquiline and Delamanid, but the limited access keeps the drugs away from the patients in a large number of countries.  
There is little progress in the case of Sutezolid, which remained dormant in the hands of Pfizer for a long time before Sequalla got the license. Sequalla has not yet announced any plans for trials in the developing world.
On their own the pharmaceutical companies are not interested in venturing into the developing world, as markets TB drugs are not attractive enough.
Affordable Diagnostics
DR TB cannot be tackled detecting it at the earliest. This requires better diagnostics tools that detect resistance which enables the physicians to prescribe the right therapy. The new diagnostics like Xpert are expensive and require frequent purchase of costly cartridges. What is required is an affordable high quality diagnostic tool.  
Concerted Steps Needed
The above background points to the need of concerted action by health policy makers to get new drugs for TB to the patients in the high burden countries. There has to be a global effort to push the clinical trials of all drugs in pipeline in the developing world where the disease is predominant. Conduct of clinical trials will require access to funds and facilities to conduct complex TB trials. The regulatory authorities in high burden countries will have to be equipped to take up registration of new TB drugs on priority. WHO and global civil society and patient groups will have to push for such measures. Unless such steps are taken WHO’s issuance of guidelines for Bedaquiline and Delamanid would only be of academic interest and useless for a majority of the afflicted. A promising candidate which is progressing in trials is PA 824 of TB Alliance which is undergoing trials in combination with other drugs. In line with its mandate TB Alliance is likely to make the drug affordable and accessible.
No such new initiatives are visible, at least in India which harbours one fourth of global TB burden. We seem to be content with the slow progress of DOTS. 
At the rate, we are going, the SDG goals are unlikely to be met, as the deadline is just 14 years away. Without globally coordinated measures to make affordable new drugs available we will still be grappling with the TB epidemic in 2030 and, Goal 3 of SDG will remain elusive for most nations.
The twinning of hope and the despair on the TB drug-discovery horizon reminds one of Charles Dickens:
It was the best of times, it was the worst of times, it was the age of wisdom, it was the age of foolishness, it was the epoch of belief, it was the epoch of incredulity, it was the season of Light, it was the season of Darkness, it was the spring of hope, it was the winter of despair, we had everything before us, we had nothing before us, we were all going direct to Heaven, we were all going direct the other way - in short, the period was so far like the present period…

1 comment:

  1. Thanks for this great article Zakir. It is indeed sad that instead of national govts. negotiating the price with these companies and bring it down to an affordable rate, they are happy to take donations. India is taking donation from J&J of 10000 course of Bedaquiline for the next few years. I am sure this trend will be followed with Otsuka for Deltyba too in near future. The big pharma seem to be having their way with no intervention from policy makers at all

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