Tuberculosis: Status in India and Bedaquiline Patent Challenge

Context:

• Two tuberculosis survivors from India and South Africa have challenged a patent to prevent pharmaceutical giant Johnson & Johnson (J&J) from extending its monopoly on Bedaquiline, one of the two newest anti-TB drugs in 50 years.
• Both survivors of drug resistant TB are now advocating for a wider rollout of newer drugs like Bedaquiline over other painful injections and drugs with severe side effects.

About:

The patent challenge has been filed with support from Médecins Sans Frontières (MSF). J&J patent application is being challenged for the salt form of Bedaquiline, which does not merit patenting under India’s patent law. If granted, J&J’s monopoly on bedaquiline would be extended from 2023 to 2027, delaying entry of generics by four additional years.

The patent application in question – for the formulation of Bedaquiline – was filed in 2007, and became publicly available in 2008, as part of standard procedures when developing new medicines. The application was first considered by the Indian Patent Office in 2012 and remains under review.

Differing views on Patent Challenge

Survivors and Médecins Sans Frontières

• To prevent an extension of the patent monopoly that will continue to block people from accessing more affordable generic versions of Bedaquiline.
• This strategy of ‘patent ever-greening’ by filing additional, often unmerited patents, is commonly used by corporations to extend monopolies on their drugs beyond the standard 20 years.
• The development of Bedaquiline benefitted from considerable public investment, and the evidence for its potential to improve cure rates with fewer side-effects was the result of a collective effort of the global TB community.
• About 558,000 people developed DR-TB in 2017, but only 25 per cent of them were treated. The standard DR-TB treatment in most countries has included drugs that need to be injected daily and are associated with several serious side-effects. The cure rate is only 55 per cent.

Johnson & Johnson (J&J)

• Company is committed to ensure that bedaquiline reaches as many patients as possible, and it is a committed partner in India’s efforts to combat TB.
• A formulation patent would not prevent generic manufacturers from developing the active pharmaceutical ingredient in their own formulations after July 2023.
• Introduction of Bedaquiline in India, J&J has donated more than 10,000 courses to support the government’s efforts to scale up access.
• Beyond providing access to bedaquiline, it has also supported efforts to improve diagnostic capacity, train health workers on the clinical management of TB, and raise awareness of TB at the community level.

Tuberculosis

It is an infectious disease caused by bacteria (Mycobacterium tuberculosis) that most often affect the lungs. TB is spread from person to person through the air. About one-third of the world's population has latent TB, which means people have been infected by TB bacteria but are not (yet) ill with disease and cannot transmit the disease.

Drug-resistant forms of TB

Misuse or inappropriate use, as well as poor quality of antibiotics have resulted into drug-resistant forms of TB. These drug-resistant forms range from multi-drug resistant TB (MDR-TB) up to extensively drug-resistant TB (XDR-TB):

Multi-drug resistant TB: It is resistant to at least Isoniazid and Rifampicin, two of the most effective TB drugs. It can only be treated with expensive, newer antibiotics over a longer period.

Extensively drug-resistant TB: It is resistant to almost all forms of medical treatment with little hope of survival for the victims.

Is Tuberculosis Curable?

Tuberculosis is curable and preventable but it is a complex disease. On the one hand, it can affect different areas of the human body, such as the lungs, the lymph nodes, the skeletal system or the brain. On the other hand, different types of TB exist, which can either be completely curable, but in the case of drug-resistant forms could also mean certain death.

Since 2000, 53 million (WHO estimates) lives have been saved through effective diagnosis and treatment. Active, drug-sensitive TB disease is treated with a standard 6-month course of 4 antimicrobial drugs that are provided with information, supervision and support to the patient by a health worker or trained volunteer. The vast majority of TB cases can be cured when medicines are provided and taken properly.

Globally in 2016, WHO estimated that 4.1% of new cases and 19% of previously treated cases of TB were of MDR/RR-TB. There were an estimated 600,000 incident cases of MDR/RR-TB. Cases of MDR-TB (490,000) accounted for 82% of the total. The countries with the largest number of MDR/RR-TB cases (47% of the total) are China, India and the Russian Federation.

TB Burden in India

As per the Global TB Report 2017, India accounts for about a quarter of the world’s TB cases (approx.28, 00,000 occurred and 4.5 lakh people died due to TB) and also shares the highest burden of both TB and MDR TB. There are an estimated 79,000 multi-drug resistant TB patients among the notified cases of pulmonary TB each year. India is also the country with the second highest number (after South Africa) of estimated HIV associated TB cases.

India also has more than a million “missing” cases every year that are not notified and most remain either undiagnosed or unaccountably and inadequately diagnosed and treated in the private sector.

Government Policy for TB control in India for last 25 Years

• In 1993, to overcome the Weakness of previous NTP, the Revised National TB Control Programme (RNTCP) was launched. The programme was based on DOTS (the internationally-recommended strategy for TB control) which promotes diagnosis by sputum smear microscopy, direct observation of treatment, standardized regimens.
• In 1997, the RNTCP was launched as a national programme with a plan to scale up in a phased manner; through the general health service infrastructure.
• DOTS was officially launched as the RNTCP strategy in 1997.
• In 2006, WHO introduced a six-point Stop TB Strategy to counter new challenges HIV-related TB and MDR-TB.
• In 2009, a revised “National Framework for Joint TB/HIV Collaborative Activities” was launched by the RNCTP and the National AIDS Control Programme.

The National Strategic Plan (2017-2025): It is crafted in line with other health sector strategies and global efforts, such as the draft National Health Policy 2015, WHO’s End TB Strategy and the Sustainable Development Goals. It is aiming to achieve elimination of TB, by 2025. During plan period, targets for TB are:

• • 80% reduction in TB incidence (i.e. reduction from 211 per lakh to 43 per lakh)
  • 90% reduction in TB mortality (i.e. reduction from 32 per lakh to 3 per lakh)
  • 0% patient having catastrophic expenditure due to TB
• TB elimination have been integrated into the four strategic pillars of “Detect – Treat – Prevent – Build” (DTPB).
• It has also linked Bank Account, AADHAR and NIKSHAY for direct cash benefits to patients.

Prevalence of disease

The implementation of DOTS under the RNTCP has improved treatment success rates and probably led to a decline in the duration of disease. WHO estimates suggest that the prevalence of all forms of TB decreased from 506 per 100 000 population in 1995 to 280 in 2007, at a rate of about 6% per year.

WHO estimates that the TB mortality rate decreased from 44 per 100 000 population in 1995 to 29 in 2007, a rate of about 4% decline per year, and giving about 335 000 deaths due to TB in 2007 . Under the RNTCP, case fatality in new cases has remained below 5% nationally but is significantly higher in districts where the prevalence of HIV in women attending antenatal clinics is greater than 3%.

Economic impact

TB is more prevalent in people living in poor circumstances and the cost of TB to patients and their families is considerable. Direct costs include transportation, and in the private sector, diagnosis and medical treatment; indirect costs include work lost or school missed for children. Some TB patients spend 20% to 40% of their annual family income being treated for TB in the private sector before reaching the RNTCP services.

TB morbidity and mortality mainly affect people in their most productive years, and impose a cost on the economy. In 1999, it was estimated that implementing DOTS in India would generate economic benefits equivalent to between 0.9% and 3.3% of GDP. An in depth economic analysis has been recently completed by WHO in collaboration with the RNTCP shows that the number of disability-adjusted life years (DALYs) lost due to TB per 100 000 people in India has improved by 33% from 1990–2006. However, TB is still the cause of substantial economic loss. In 2006, TB caused a loss of 7.9 million DALYs and a reduction of US$ 23.7 billion in economic well-being (equivalent to US$ 21 per capita). The cost of TB control averaged just US$ 26 per DALY gained over 1997–2006 and generated a return of US$ 115 per dollar spent.

Budgetary provisions:

Between 2002 and 2009, the annual budget for TB control in India grew from US$ 36 million to US$ 100 million.

In 2019 Budget, Government has allocated Rs 1200cr for social and nutritional support to TB patients under national strategic plan. The cost of implementing the new NSP is estimated at USD 2.5 billion over the first three years (2017-2020), a steep increase over the current budget.

Conclusion:

 India has scaled up basic TB services in the public health system, treating more than 19 million TB patients under RNTCP. But the rate of TB decline is too slow to meet the goals of NSP (2017-2025) and 2030 SDG and 2035 End TB targets.