Tag: delamanid

Anti-Cancer Drugs, Anti-Infectives Added to National List of Essential Medicines

As many as 26 drugs such as Ranitidine, Sucralfate, white petrolatum, Atenolol and Methyldopa have been deleted from the revised list.

New Delhi: Thirty-four drugs, including some anti-infectives such as Ivermectin, Mupirocin and Nicotine Replacement Therapy, have been added to the National List of Essential Medicines taking the total drugs under it to 384.

Several antibiotics, vaccines and anti-cancer drugs will become more affordable by their addition to the list.

However, 26 drugs such as Ranitidine, Sucralfate, white petrolatum, Atenolol and Methyldopa have been deleted from the revised list.

The deletion has been done based on the parameters of cost effectiveness and availability of better drugs.

Union Health Minister Mansukh Mandaviya, who released the list on Tuesday, tweeted, “Released the National List of Essential Medicines 2022.It comprises 384 drugs across 27 categories.Several antibiotics, vaccines, anti-cancer drugs and many other important drugs will become more affordable & reduce patients’ out-of-pocket expenditure.”

Endocrine medicines and contraceptives Fludrocortisone, Ormeloxifene, Insulin Glargine and Teneliglitin have been added to the list. Montelukast, which acts on the respiratory track, and ophthalmological drug Latanoprost figure in the list.

Cardiovascular medicines Dabigatran and Tenecteplase also find place in the list besides medicines used in palliative care.

“Antinfectives such as Ivermectine, Meropenem, Cefuroxime, Amikacin, Bedaquiline, Delamanid, Itraconazole ABC Dolutegravir have been added to the NLM,” Dr Y.K. Gupta, Vice Chairman of the Standing National Committee on Medicines, said.

The drugs in NLEM are included in scheduled category and their price is regulated by the National Pharmaceutical Pricing Authority, Dr Gupta said.

A revised list of 399 formulations was submitted by an expert committee under the Indian Council of Medical Research (ICMR) last year. After detailed analysis of Indian requirements, major changes were sought by Mandaviya.

As Focus Moves to TB Prevention, Who Will Treat India’s 2.69 Mn Patients?

At a recent global conference in Hyderabad, pharmaceutical companies and funding agencies seemed keen on TB prevention. But what about treatment of those already suffering from it?

Between the TB bacteria and the world’s best scientists, it’s not yet clear who will win. TB is still the world’s deadliest infectious disease and India has the world’s highest burden of TB with 2.69 million people.

It’s crunch time for the world when it comes to TB. The 4,000 people who gathered at Hyderabad last week to discuss how to eliminate TB certainly think so. The global goal for this is the next 10 years, but India has committed to eliminate TB in five years.

So far, the deadly TB bug has put up a stiff fight. There were 10 million new cases of TB just last year and the fall rate is low. As many as 1.2 million people died last year from TB. One must remember that TB is curable, so this high death toll suggests that these people did not get adequate treatment.

One of the world’s oldest health institutes, The Union, holds an annual World Conference on Lung Health. This year is the 50th anniversary of this global conference and it was finally held in India, where the world’s largest TB population lives.

All the buzz at the conference this year was on TB prevention. Big pharmaceutical companies like GSK, Sanofi and Otsuka were celebrated for their announcements about vaccines, drugs and trials on prevention of TB. The US’s National Institutes of Health (NIH) announced two large tranches to fund more work on TB prevention, offering nearly $100 million to this end. But there were no big announcements on making TB treatment more accessible or affordable or on ways to funnel new research into treatments.

Also read: Govt Stalls Payments to 26 Lakh TB Patients Over Suspicious Transactions

Treatment as a form of prevention

“Treatment itself is a form of prevention,” says Yogesh Jain, a doctor at the Jan Swasthya Sahyog in Chhattisgarh. “When we successfully test, diagnose and treat people for TB, we prevent the disease from spreading further and we also save the lives of those affected by TB.”

Credit: Global TB Report 2019

After all, 10 million people are estimated to have fallen ill with TB in 2018 alone, according to the World Health Organisation. Over 1.2 million people died from TB in 2018, a number which is particularly staggering in the light of the fact that TB is curable. So while prevention is important, is the global health community doing enough to treat those who are already struggling with TB, including India’s 2.69 million?

If treatment is unaffordable, will prevention be affordable?

As Dr Jain says, diagnosing and treating TB is itself a mechanism that will prevent the spread of TB. But has India been able to successfully do this? And what are the internal and external factors that are impeding India’s ability to diagnose and treat TB?

At the Union conference this week, the US’s NIH announced that it is launching a massive “prevention trial” with Otsuka’s Delamanid to see if it is effective in preventing TB. Delamanid is already recommended as a drug for curing TB. This new trial is going to happen in 12 developing countries, including India. As many as 5,610 people will be enrolled in this trial. Otsuka is donating the drugs needed for this trial. NIH is pumping in nearly $65 million.

Also read: TB Survivors Disrupt Global Conference, Demand That Drugs Be Made Cheaper

However this lifesaving drug is unaffordable for Indian patients. The Japanese company is offering to sell the drug for a price of Rs 1.19 lakh ($1,700) for a treatment course. Neither can an average Indian patient afford to buy this individually, nor can the Indian government procure the drug en masse at this price.

Even if this new trial is successful, a spokesperson at the NIH said that their funding of this trial comes with no obligations on Otsuka, which will not be obliged to make this drug available to the countries where they did their trial.

So essentially, Otsuka will be able to do their new trial of this drug on Indian patients but Indian patients themselves cannot afford this drug now or perhaps, later.

The Wire reported earlier this year that a declaration being deliberated upon at the United Nations this year removed clauses which compelled countries to ensure that TB drugs are affordable. Clever manoeuvring by Indian and South African diplomats had managed to restore such clauses.

A new TB vaccine

Elevated discussions on disease often pick solutions that are expensive, when in fact, in countries like India, even nutrition is a challenge. But nutrition is vital in preventing TB, like a vaccine.

“If people are well nourished, it protects them from many diseases, not just TB. Well-nourished people are less likely to get TB and more likely to respond well to TB treatment,” says Jain. And while Jain would like to be able to give his patients more of these lifesaving TB drugs, he says his hospital in Chhattisgarh which serves hundreds of patients everyday, is unable to get it from the government.

Also read: New TB Vaccine Gets More Efficient; Another $30 Million Allotted for Research

One of the first press briefings at the conference last week was GSK’s announcement of their new M72 vaccine for prevention of TB. Although GSK takes credit for the it, the vaccine has in fact received tremendous tax and philanthropic funding from the governments of the UK, the Netherlands, and Australia, and from IAVI and the Bill and Melinda Gates Foundation. It has not been solely funded by GSK.

The company has done a small trial but says they will need more money to do further trials. The NIH also announced a $ 30 million fund for research on TB vaccines.

And yet GSK executives at conference refused to put a price on what the vaccine may cost to patients.

As is the trend with nearly all major drugs, including Bedaquiline and Pretomanid, tax money is often used to develop a drug which is not made affordable to the tax paying public.

Once again, the high prices of these lifesaving TB drugs means that even though India has the highest burden of TB in the world, neither can the Indian patient nor can the Indian government afford to buy them. Otsuka is offering Delamanid at $1,700 (Rs 1,19,887) per course, Bedaquiline at $400 (Rs 28,208) per course and Pretomanid at $364 (Rs 25,670).

Many of these drugs have to be taken in combination with each other, raking up the price of treatment. Treatment can go on for at least six months if not more.  India has, so far, not bought any of these drugs and has taken donations of 22,000 courses of Bedaquiline and 400 courses of Delamanid. Executives at these drug companies told The Wire last week that they are not giving any more donations to India.

With all this fresh money coming in for prevention of TB and no interest so far from India to wrestle down the price of TB treatment with pharma companies, India’s 2.69 million TB patients will be left in the lurch.

“In an ideal world, if the TB budget was adequate, all countries will do everything: They will be able to do prevention and manage active and DR-TB with high quality care and also do active case finding,” says Dr Madhukar Pai, director of McGill International TB Centre.

However, he says, in reality, TB budgets are low and thus “countries have to make hard choices, and most will give priority to correct and active TB treatment, and also improve DR-TB care. If we want developing countries to do more prevention activities, then we need to give them the fiscal space to add these new interventions.”

The Indian government has coined a new slogan this year for its TB campaign: ‘TB harega desh jeetega’ (‘TB will lose, the nation will win’).

Right now, however, the TB bug appears to have the lead in the race to 2025.

Anoo Bhuyan was in Hyderabad reporting as one of ‘The Union’s Media Scholars’ at the 50th Union World Conference on Lung Health.

TB Survivors Disrupt Global Conference, Demand That Drugs Be Made Cheaper

Companies owned by people in the Global North control the science and business of TB, making medication unaffordable for poor people in developing countries.

Hyderabad: “F*@#ing killing me! Don’t kill me! This is my life. I don’t want to die…We want medicines. We are dying here. God save us…F*@#ing patents.F*@#ing monopolies. This is my life…”

That was Ganesh Acharya, shouting in front of a global audience of scientists, doctors and others in the public health sector, demanding that tuberculosis drugs be made cheaper and accessible to people like him in the developing world.

Acharya knows about this the hard way: he has survived TB twice and has committed his life to working for TB and HIV patients in India.

Acharya was shouting himself hoarse along with a number of TB survivors and health activists who had come to the renowned World Conference on Lung Health organised by The Union in Hyderabad last week.

TB survivors used the opportunity to repeatedly confront the global audience about the unaffordability of TB drugs, especially by people in the developing world where the disease hits the hardest. India tops the world with 2.69 million TB patients, 27% of the world’s TB burden.

After the protest by Acharya and other TB survivors, Sambuddha Ghosh, an Otsuka Pharmaceutical scientist, took the mic to respond to them: “We do acknowledge that the price is high but we are working on it.”

Also read: New TB Vaccine Gets More Efficient; Another $30 Million Allotted for Research

Otsuka makes the life-saving TB drug Delamanid, which the company is selling for a minimum price of $1,700 (Rs 1,19,887) for one course. Delamanid is often taken along with other drugs like Bedaquiline, which is being sold for $400 (Rs 28,208) per course.

TB survivors and activists were not impressed by Ghosh’s muted response and continued their protest: “Otsuka! Drop the price! Delamanid ke patents se azaadi (Freedom from the patents on Delamanid)!” they shouted, as they held up posters, distributed flyers to the audience and then left the hall.

TB’s disproportionate burden on the developing world 

TB survivors also disrupted a session where a top executive from Cepheid was present. Cepheid makes the important diagnostic tool called GeneXpert and there was due to be a discussion on how important their product is while diagnosing TB.

TB survivors stormed this session and shouted slogans saying that GeneXpert’s technology was developed primarily with public tax money from the US and UK. Apart from the fact that the machine itself is expensive, the cartridges that need to be refilled in it are also adding to the cost of using this technology.

Survivors shouted, “What time is it? It’s time for five!”

According to calculations made by TB survivors and activists from Médecins Sans Frontières and Treatment Action Group, cartridges should be priced at $5 in order to make it viable for the company but also affordable for TB patients. Nearly 12 million cartridges have apparently been sold in 2018, just in the public sector.

Also read: Health Care Is an Essential Human Right – and so Is a Proper Diagnosis

Phillipe Jacon, a senior Cepheid official, addressed them and said, “We appreciate everything the activist community has said here.” He said his company has received a number of questions from the activists and that Cepheid would respond in a week.

The tension between pharmaceutical company executives and the TB survivors pointed out to the unequal burdens of TB: TB is a disease of poverty and a disease of the developing world. All the high burden countries in the world for TB, led by India, are all in the developing world. But companies owned by people in the Global North control the science and business of TB, making it unaffordable for poor people in developing countries.

The Global North has already dealt with TB and no longer faces a crisis. In some Western countries, their entire TB burden is in double digits, whereas India has 2.69 million TB patients. 

One clear example of the burden of TB is in travel visas: Indians who wish to travel to the UK for a long period have to get screened for TB before being given a visa. This ensures that TB is contained in developing countries.

TB drugs unaffordable for developing world

TB survivors disrupted at least four sessions at the conference in which pharmaceutical company officials were speaking. They demanded that companies and organisations like Johnson and Johnson, Otsuka, TB Alliance and Cepheid bring down the prices of life-saving drugs and diagnostics.

Survivors were particularly interested in and protested against the high prices of Bedaquiline (made by Johnson and Johnson), Delamanid (made by Otsuka), Pretomanid (which was developed by the TB Alliance) and the GeneXpert diagnostic (made by Cepheid).

TB survivors also staged an intervention at the opening ceremony of the global conference. Soon after Vice-President of India Venkaiah Naidu left the hall, TB survivor Nandita Venkatesan did a Bharatanatyam dance performance.

She delivered a rousing speech after that, demanding that the global community stops making decisions for TB patients without thinking of patients’ best interests. “Nothing about us, without us,” she said.

As she wound up her speech, about 50 TB survivors and activists took the stage. “This disease is not just about the science. It’s about those who lost their lives to the disease and the rights of those affected with the disease,” they said.

Also read: Dying in Dust: For Rajasthan’s Miners, Silicosis Deepens Struggle With TB

Another session where they protested at was the announcement of a new drug which is poised to be an important breakthrough in TB treatment. Pretomanid is the new drug making a buzz, as it has recently been approved by the US drug regulator.

Pretomanid, Bedaquiline and Delamanid are the only three drugs that have entered the scene in the last nearly four decades with any hope of treating TB. However, the TB Alliance says it will sell the drug at a minimum price of $364 (Rs 25,670). This drug too will need to be taken along with Bedaquiline and Linezolid and the cost of the entire regimen and course will be $1,040 (Rs 73,342).

Pretomanid has been developed by the TB Alliance with taxes and philanthropic money. TB Alliance is registered as a non-profit and not as a pharmaceutical company. So activists and survivors say they are surprised that TB Alliance has decided to file for patents in several countries, has licensed the drug out to only two pharmaceutical companies for manufacture and will sell the drug in only select markets, and has not published any of their data from their very small trial of the drug.

TB survivor’s shouted at a panel discussion with top officials of the TB Alliance: “Whose drug? Our drug!”

Mel Spigelman, president of the Alliance, then took the mic but refused to address any of the concerns raised by the survivors and activists. He told the audience, “This is not the forum to discuss this issue.”

Anoo Bhuyan was in Hyderabad reporting as one of ‘The Union’s Media Scholars’ at the ‘50th Union World Conference on Lung Health’.

India Looks to Expand TB Programme With New Drug Bedaquiline

The health ministry has said that drug-resistant TB patients will be put on an injection-free – so entirely oral – regimen.

New Delhi: Taking the lead from South Africa, India is also looking to get all drug-resistant tuberculosis patients on to the new and breakthrough drug Bedaquiline, made by pharmaceutical company Janssen.

India has the highest TB burden in the world, and the Modi government has pledged to eliminate TB by 2025, despite the global goal being 2030.

The ‘India TB report 2019’ was launched on Wednesday, detailing the annual progress of India’s TB control programme.

At a press conference in Delhi, Vikas Sheel, a senior bureaucrat in the Ministry of Health, explained the government’s plan for TB treatment. He said that drug-resistant TB patients will be put on an “injection-free regimen”.

An injection-free regimen would be an entirely oral regimen, which will save patients the hardship of painful injections. The drugs in TB injections have left many patients deaf. Having injections in a regimen also makes it hard for unwell patients to keep coming to meet doctors, especially in far-flung areas, in order to take their injections. An entirely oral regimen will help in this regard as well, because patients can take the medicines at their own homes.

An entirely oral regimen also means that patients will be moved off painful injections and on to Janssen’s oral TB drug, Bedaquiline. At some point, more patients will also be put on another oral drug, Delamanid, made by Otsuka.

Also read: TB Killed Shreya Tripathi, But Her Death Could Have Been Avoided

Writing in the TB report, Dr K.S. Sachdeva says, “The introduction of Bedaquiline and Delamanid along with a shorter regimen of 9-11 months for drug resistant TB patients, has made it easier for those with MDRTB to complete their treatment. There has been an increase in proportion of patients on injection-free drug regimes, which went up from 67% in 2017 to 98.5% in 2018.” Sachdeva is the head of India’s central TB division.

The report says that “India envisages implementing injection free regimen for all TB patients” and that they have taken a “policy decision on discontinuation of regimen for previously treated TB patients”.

Some public health activists say just expanding Bedaquiline access is insufficient and the government also needs to take a decision on expanding access to Delamanid. This means negotiating with Otsuka Pharmaceuticals to bring down the price, and begin giving Delamanid in conjunction with Bedaquiline, for pre-XDR and XDR TB patients.

The government’s announcement of an all-oral regimen today is a “welcome step”, says Leena Menghaney from Doctors Without Borders. But she says an injectable-free regimen is not possible for all drug-resistant TB patients, especially those with fluoroquinolone resistance, “until both Bedaquiline and Delamanid are made available together for patients with pre-XDR and XDR TB”. She says the high price of Delamanid ($1,700 for six months) creates a “chilling effect on the willingness of TB programmes to scale up the drug”.

The government’s TB report also says that one of the “major achievements” in 2018 is the “successful completion” of the conditional access programme for Bedaquiline. Based on this, they are now feeling confident about a “pan-India expansion of Bedaquiline access”.

A total of 1,669 patients were put on Bedaquiline for this. It was initially tried out in five states in 2016-2017 (Assam, Delhi, Gujarat, Maharashtra and Tamil Nadu). In 2018, 2,827 patients were put on the drug. In total, nearly 3,000 patients have been given Bedaquiline through the government programme since 2016.

The government is now looking at a “country-wide expansion” of regimens containing Bedaquiline.

Also read: India’s TB Patients Need Bedaquiline Now, Never Mind the Critics

What is Bedaquiline?

Bedaquiline in India has been hard fought. Initially, the Indian government was willing to give the drug only in five government centres. Then a young TB patient named Shreya Tripathi went to court asking the government to give her access to the drug. The World Health Organisation’s committee of experts has been assessing this new drug every year, and coming back with more and more encouraging reviews.

Slowly the Indian government too has been rolling out the drug more widely. The announcement today signals that they are ready to take it much further and give it to all TB patients who may be resistant to certain drugs.

Phase three clinical trial data has not been released by Janssen about this drug and the Indian government’s conditional access programme was not run as an official clinical trial either. But public health professionals have been proceeding anyway, based on the WHO’s advice and data coming out of programmes like in South Africa.

Although India has only put about 3,000 patients on Bedaquiline, the government was given a donation of 10,000 courses of the drug through USAID. The government says that 6,750 courses of this have been delivered and the rest were scheduled to be given to patients by March 2019, though it has not confirmed if this was done. The Indian government requested USAID for another 10,000 courses of Bedaquiline in 2019.

Only Handful in India Will Have Access to TB ‘Wonder Drug’ Delamanid Next Month

Four-hundred doses of Delamanid, one of the last known drugs in the arsenal against multi-drug resistant tuberculosis, will be sourced by Indian pharmaceutical company Mylan from its Japanese manufacturer Otsuka.

Mumbai: In less than a month from now 400 patients, across seven states in India, will have access to a life-saving tuberculosis (TB) drug called Delamanid – one of the last drugs in the world’s arsenal against drug-resistant TB. These are patients who have stopped responding to most of the known TB drugs, and some of them have stopped responding to all TB drugs.

Living under the onslaught of the TB bacteria, all they could do was wait. That is set to change now – but only for a handful.

“We will get 400 courses of Delamanid within a month and patients will have access to it under the government’s conditional access programme (CAP),” Sunil Khaparde told The Wire on the sidelines of the TB symposium organised by the Family Welfare Training and Research Centre in Mumbai.

These 400 courses of Delamanid will go to patients in Punjab, Chandigarh, Rajasthan, Karnataka, Odisha, Kerala and Lakshadweep, across 21 centres under the government’s Revised National TB Control Programme. They will be free of cost to the patients. Globally, a six-month course of Delamanid costs $1,700 per patient (Rs Rs 1.16 lakh).

One-tenth of India’s drug resistant TB patients are in Mumbai, and they will not have access to Delamanid, nor will the patients in the private sector.

“The centres are spread across states which weren’t the first to get bedaquiline,” Khaparde told The Wire.

Indian has close to 2.8 million new TB cases every year. That means one in every fourth TB patient on the planet calls India home. Of this, nearly 2.8% of the people will not respond to most known TB drugs. Among the existing TB patients who have had a relapse, one in ten will not respond to most drugs.

Delamanid comes as a relief to this group of patients. However, the states with the highest drug-resistant TB burden have been kept out for now.

Maharashtra alone has over 8,000 patients with multi drug-resistant (MDR) TB, closely followed by Uttar Pradesh. Between the two, they have nearly 1,500 extremely drug resistant (XDR) TB patients. What’s worse, while these states have access to the drug bedaquiline, children with drug resistant TB and patients with HIV/TB co-infections don’t have any drugs. Bedaquiline is not suitable for these two groups as it is likely to do them more harm than good. And in its absence, they have no alternatives.

“Areas with the highest drug resistant TB burden should have access to the drugs,” said Syed Imran Farooq, country director for Challenge TB, a USAID-funded project that pushes for greater access to new drugs and regimens for patients.

Delamanid is the only drug that the WHO has approved for use in drug-resistant TB patients as young as six. The B.J. Wadia hospital for children in Mumbai, which has India’s only paediatric TB ward, will not have access to Delamanid.

‘Current drugs never tested’

“It is important to understand that the TB drugs that are currently used on thousands of drug resistant patients have never been clinically tested and have terrible side effects like permanent hearing loss,” explained Jennifer Furin, an infectious diseases specialist and medical anthropologist, Harvard Medical School. “After bedaquiline, Delamanid is only the second new TB drug in 50 years. It is both effective and a safe medication that can even be given to children,” she said, questioning the government’s rationale in restricting access to the drugs.

Most clinical trials don’t enroll children. As a result of this, when the drugs are out, it is difficult to know their effects on children. However, “the Delamanid trials involved children and there is data about the efficacy of the drug for the group,” Furin said.

India reports nearly 423,000 TB deaths every year – or one in three TB deaths in the world.

The US-based generic drugs manufacturer Mylan will be distributing Delamanid under an agreement with Japanese pharmaceutical corporations Otsuka in India. In a statement to The Wire, Mylan confirmed that they had initiated a technology transfer process with Otsuka so that, in the future, Delamanid could be manufactured in India. Mylan said it expects many paediatric cases to be in the 400-patient group who will get the drug.

“The first step is to have the drug in the country’s TB programme. But the delay is due to Otsuka. For years, despite holding a patent monopoly, it delayed filing the dossier for registration of the drug in India,” Leena Menghaney of Doctors Without Borders (MSF), an international organisation fighting for access to medicines for patients in the developing world, told The Wire. MSF has been providing a handful of patients access to both bedaquiline and Delamanid in India on compassionate grounds. The successful results were published in the journal Lancet in May this year.

When Otsuka did file to register the drug, it failed to include the paediatric indication. The government can approve the use of a drug only when a pharmaceutical company applies, which Otsuka delayed doing for years.

At the moment, the Indian government maintains that they are getting the drug as a loan from the Japanese government. “The terms have not been made public, so we don’t know the extent to which it will affect access to medicines,” Menghaney said.

Countries like South Africa, which also have a large number of drug-resistant TB cases, don’t just provide access but give their patients an oral dose of bedaquiline unlike – India where patients still have to take painful daily injections for as long as six months.

While India has committed itself to eliminating TB by 2025, this they will need to reduce the number of new cases by 15-20% every year to do this, by the government’s own admission.

Some drug resistant patients who will need both bedaquiline and Delamanid are also not going to be given the combination. “The whole system of restricted access makes no sense. 2025 is in seven years. Restricted use of innovation is certainly not a way to end TB,” Furin said.

Disha Shetty is a freelance science journalist.

Interview: ‘You’re Going Into a Battle on Tuberculosis, and You Need to Have an Army’

Narendra Modi recently reaffirmed India’s commitment to eliminating TB by 2025, five years before the rest of the world. The executive director of the ‘Stop TB Partnership’ spoke to The Wire about the road ahead.

Last week, India hosted the ‘Delhi End TB Summit‘, with a host of world leaders including the World Health Organisation’s (WHO) director-general, Tedros Adhanom Ghebreyesus. India has the world’s highest population of people living with tuberculosis (TB), including about one million who are estimated to not yet be diagnosed. At the summit, Prime Minister Narendra Modi said, “I am confident that India can be free of TB by 2025.”

The Wire’s Anoo Bhuyan interviewed Lucica Ditiu, the executive director of the ‘Stop TB Partnership’, a global network of organisations working to eliminate TB while consolidating political support for it. The partnership cohosted the summit along with WHO and the Indian government. Ditiu discussed India’s plan to eliminate TB by 2025, which is five years sooner than the global target of 2030. She also discussed issues around access to drugs for drug-resistant TB and civil society’s demands for the Indian government to force cheaper production of these drugs.

As someone who has been tracking TB for a long time, where do you see India- What are we doing right and wrong on TB at this moment?

LD: I see India doing very good things, now. They have not covered the entire country and the scale is obviously not there- we’re speaking of a country with the largest scale of TB patients that one can think of. But in terms of policy and the National Strategic Plan, most of the things that should be done, are there. I think finances for the plan are increasing. So in terms of what should be done, the mindset, the political and financial commitment, things are not bad. Not perfect. But it’s a very good beginning.

I’ll tell you what needs to be worked on. There are two things in my opinion. Firstly, India plans to end TB by 2025. Ending it doesn’t mean it will go to 0 people with TB. There is a definition at the global level. Currently, India’s level is more than 200 per 1,00,000 people. The definition of zero TB, is 10 per 100,000. It’s a long way to go, as you know. But the important thing is, now we’re in 2018, so, to eliminate TB by 2025, we need to make an intensive effort. The country and its leaders should know that the same level of enthusiasm and energy that we see now needs to persist for the next 7 years. This is the biggest challenge because it’s very difficult to maintain the engagement, political commitment, effort and funding. For me this is a huge threat because if something else becomes more important than TB, India will not achieve its goal of eliminating TB.

My second worry is about the implementation arrangements. This is related to the fact that you can have the best decision and the funding, but there are many steps from the capital in Delhi to the smallest village in Delhi. The real distance is also in the mind. At this huge scale, the systems should be constructed and put to work so that this becomes possible.

Dr Lucica Ditiu, Executive Director of the Stop TB Partnership. Credit: StopTB Partnership

Lucica Ditiu, executive director of the Stop TB Partnership. Credit: StopTB Partnership

This is what I want to say to the government, that it will be extremely important to have the mind to think this for India. At this scale, you’re going into a battle with TB, and you need to have an army. The worst thing can be that all of these things are available, but because of bureaucracy, legislation and complications, things don’t get implemented. It’s not just India, this has happened in many other places as well.

India’s goal is to eliminate TB by 2025, which is 5 years sooner than the rest of the world. But we also have the largest TB population in the world. After these days of deliberations with the Indian government, what is in place and what is not in place?

LD: This is very much linked to the first question. What is in place as I said, is an incredible political commitment. I have to tell you that Prime Minister Modi is the only head of state currently of such a large nation that came out there and set up a very bold target, asked for a strategic plan and personally monitors what’s going on. Funding is increasing, I understand. I understand the government has plans for nutritional support of TB patients very soon.

What I think needs to be worked on, as I said and everyone is aware of, implementation arrangements need to be done. How do you expand? You need to have a very large management team beyond the technical capacity, at the central level and state levels. That’s why the ministries of state are very important and they came as well for the summit.

But specifically, what is not in place? What can you prescribe to India, on the biggest, most gaping holes?

LD: The plan is there. I don’t think there are things that are hugely missing. If we want to make the impact of ending TB by 2025 which is proposed in the national strategic plan, then good. The plan just needs to be implemented.

We also realised recently that India has been under-reporting TB. That’s because of the complicated architecture of the health systems. There are a lot of cases that come to the private sector but they haven’t been tabulated in Indian records. What do you make of the scale of TB in India and what needs to be done to get a more accurate picture of the scale?

LD: This is very correct. It is estimated that maybe a million people with TB are consulting the private sector every year and little is known about what is going on with them- so, regulating the private sector is an important part of ending TB and is a part of the national strategic plan. The scale is large here, in terms of the private sector. There are many types of private hospitals, like your big private networks. But also there are very small cabinet type providers all over, which are the first entry points for many patients. So, there is an entire component in there to bring them on board in different ways.

For a long time, WHO promoted public-private mixes. But at that time, in their perspective, they were sort of obliging the private sector to play ball. That does not work with the private sector. There needs to be thoughts about models that work in other places- to give a carrot to the private sector for them to report TB, but also to continue to provide care to those with TB. This is part of the national strategic plan. It’s not a new thing coming from me. It is there. As I said, implementing it and going with it beyond big cities, to every single state, that is the challenge.

What is your stand on the TB drugs Bedaquiline and Delamanid for drug resistant TB? I have seen your tweets on this. Where do you stand and what do you think India should do on this?

LD: Bedaquiline and Delamanid are two good drugs, but not the drugs that will cure TB on their own. They are drugs to be added to another regimen. According to WHO, its not for everybody. It’s for a subset of a subset of patients. There are about 40000 people who might need it in India but not more than that. But for more than 2 million people with TB in India, this is very small number. And WHO and international recommendations are saying that it should be given under certain conditions. So it’s a very good drug. They are two very good drugs to make life of people with certain types of TB much easier.

India has access to Bedaquiline as part of a donation between USAID and Janssen currently. I understand, that the Government of India entered into a discussion to see what they can do from 2020 onwards. By then we may get new regimens that include these drugs but will be shorter. So hopefully, many things for India and the world will change by then.

But what I want to say, as I told our colleagues in civil society, is that India should accelerate diagnosing people with drug resistant TB this year. Because Bedaquiline and Delamanid are for these people. In order to give the drug, you need to have people diagnosed. This part of the strategic plan needs to be implemented. To diagnose people and put them on treatment.

These two drugs have some side effects. Any drug will have side effects. However, the side effects of these drugs are linked to cardiovascular systems, so you need to have proper systems to monitor these drugs. You cannot give it to me and say “Lucica, go and be somewhere in a village and I’ll see you in three months,” because in the meantime if I get side effects, I need to see a doctor and have a conversation about it. To really scale up Bedaquiline and Delamanid, you need to ensure you have the ability to diagnose these people, and the right system in place to monitor them.

So I think this is a good opportunity to build all this while this donation programme still exists. And then go to 2020 on a bigger scale. I think this is the plan of the government.

On the issue of Bedaquiline and Delamanid, phase 3 trial data has not come in from anywhere in the world. Phase 3 trials have not even been conducted in India. In light of this, what is keeping you confident about Bedaquiline and Delamanid, and their safety and efficacy?

LD: South Africa is using Bedaquiline and Delamanid a lot in their clinics, but under the conditions I told you about, because WHO has issued clear standards. Under those WHO standards, evidence from the field, like South Africa, is very encouraging for people who have a very bad prognosis. People with several months of multi-drug resistant treatment, who were not doing well, did very very well after treatment with Bedaquiline. But indeed, we need more evidence to go at the huge scale and that’s what WHO is preparing itself very soon for, looking into whatever data is coming in.

Even in the US when [Bedaquiline] was given an accelerated approval, Janssen was told to come back with the data. That was in 2012. Does it worry you that the data hasn’t come out so far? Why don’t we have this data yet?

LD: My focus now is very much on the scale of the programme. I don’t know the real answer to this.

The Indian government does waive off phase 3 trials, but that is when phase 3 has been done somewhere else.

LD: We spend a lot of energy on Bedaquiline and Delamanid. I don’t think that pays back. I think that’s a very good discussion but there are many questions to be answered on this and they have to go in parallel. To properly treat multi-drug resistant TB, you need a cocktail of drugs. These two drugs, the research phase in South Africa, show good results, for small groups of people. You know what I mean? But speaking of treating two million people in India, and finding one million in the private sector, is a huge undertaking. And I’ll be very happy for India to find more people in need of Bedaquiline and Delamanid. They can have as much as they want next year. That’s what I’m focused on. I don’t think I’m the right person to comment on the pure research of Janssen and what they’re doing on the trials.

Confidence usually it comes from data, but the data has not yet come in. A letter has been signed by 60 individuals and organisations worldwide asking India to make this drug accessible. I’m trying to understand what this is based on. Where do you stand on this letter asking India to issue a compulsory license on the drugs? This would allow generic companies to make the drug at a cheaper price. Is this what India needs to do?

LD: To be honest, I think the letter was very limited. I was very disappointed. Civil society in India should ask, where is the missing million? They should ask the government to work with the private sector and find those. Making all that effort in a letter only on Bedaquiline and Delamanid, I don’t think will move the needle. If I was in civil society, I would want to ask for every single person in India to have quality care and treatment. That’s what they should ask. By going piecemeal and speaking only about Bedaquiline and Delamanid now in 2018, when we don’t know how it works, when we don’t know how many people need it, for me was a missed opportunity. It was a bold letter. But new tools, new drugs, new regimens, more money for research, should have been part of it. That should have been something in it.

If the focus is trained on Bedaquiline and Delamanid, are we missing something else?

LD: They just need to implement the national strategic plan. If India can do that, it will be kilometres ahead. The attention should be on finding everyone with TB, diagnosing them and putting them on treatment. And I think if the civil society wants to move, and interact with the government, then they should ask to be part of not only developing the implementation plan, but also monitoring it. Civil society should be watching and asking if the money for nutrition reaching people, if the diagnostic technology accessible, etc. That’s what I think civil society should do- organise themselves to be a part of the solution and also a part of the monitoring.

India is being criticised for being slow on the access to these drugs. Given what we know – that the drugs are showing good results, but we don’t have all the data. That there are other issues which India also needs to simultaneously attend to. That infrastructure for monitoring needs to be in place, but India is challenged on that… Given all this, is it wise for India to continue on a conservative conditional access programme as it is currently doing? Or open the flood gates?

LD: I don’t know. As I keep saying, I’m looking at this from a different perspective. More data is needed for these two drugs, to understand how they work, how they interact with each other, with HIV drugs, with children. We need to know more. South Africa is providing more evidence. A time might come – in fact, it already has come – when we will put these two drugs together and see, what if we put other innovative ideas and obtain a regimen that can be just four or five months in length…

So we cannot afford to throw these drugs into a population, create resistance to them and lose them. In terms of whether India will scale or not, I don’t know. But the need for more data is very great.

Japan’s Otsuka Aims to Apply For TB Drug Approval in India Within 90 Days

Health experts say expanded access to the drug is key for India to achieve its ambitious goal of eliminating TB by 2025.

A patient suffering from Tuberculosis rests inside a hospital in Agartala, capital of India’s northeastern state of Tripura, March 24, 2009. Credit: Reuters/Jayanta Dey/Files

Mumbai: Japanese drugmaker Otsuka Pharmaceutical aims to apply for approval of its tuberculosis (TB) drug delamanid in India within three months, a senior company official said, as calls grow for expanded access to the life-saving medicine.

India accounts for about a quarter of the world’s TB cases and experts say improved access to delamanid in the country is critical to control the global spread of drug-resistant strains of the airborne disease.

Otsuka had an initial meeting on the matter with the Drug Controller General of India (DCGI) in late 2016, Marc Destito, communications director of Otsuka’s global TB programme, told Reuters on Monday.

“A follow-up meeting with the DCGI is currently envisioned within the next month to discuss next steps,” Destito said.

There is no clear timeline on when the DCGI will decide on the approval but the submission of the application would start a process that could eventually give thousands of patients with drug-resistant TB in India access to the last-resort drug.

Otsuka Pharmaceutical, a subsidiary of Otsuka Holdings, has had a patent on the drug in India for eight years but it has not yet applied for approval to launch it, drawing criticism from international health experts and activists.

Health experts say expanded access to the drug is key for India to achieve its ambitious goal of eliminating TB by 2025.

Only a few dozen eligible patients in India have been able to get the drug on request since it was first approved in the EU in 2014 and thousands more need it.

India’s public health system had about 79,000 drug-resistant TB patients at the end of 2015, according to the World Health Organisation’s (WHO) Global Tuberculosis Report.

Actual demand is probably higher, though, as roughly 60% of TB patients in India are treated by private clinics.

Destito said Otsuka has held initial talks with the Indian government about making some 400 courses of delamanid available at select treatment centres after approval under a conditional access programme.

Otsuka is also in talks with the WHO and the Indian Council of Medical Research (ICMR) about making delamanid available to patients in India through a clinical trial later this year.

The study would include patients resistant to most standard TB drugs who need delamanid and Johnson & Johnson’s bedaquiline, said ICMR head Soumya Swaminathan, adding that initial talks suggested up to 500 patients could be included.

Delamanid and bedaquiline are the first new TB drugs to be introduced in decades and experts say their rollout has been slow globally to ensure patients do not become resistant.

(Reuters)