How push from survivors and an HIV support group led to a cheaper tuberculosis drug

Doctors had given up on Phumeza Tisile, a 31-year-old South African who was first diagnosed with tuberculosis in 2010. They asked her “to consult a priest to prepare [her] soul”.

It was a doctor with Médecins Sans Frontières, an international medical relief organisation, who came across her case. Tisile had caught an extensively drug-resistant form of tuberculosis. The doctor managed to procure the drug that could cure her – linezolid.

“I was lucky to be in a certain place at a certain time. And I survived,” said Tisile.

Her treatment took three years and eight months. But, as a result of the medication’s side-effects, Tisile lost her ability to hear.

As she recovered, she thought of those who had no access to the expensive and patented drugs that could cure the infectious disease.

At that point, in 2013, apart from linezolid, bedaquiline was a new entry to the list of few drugs that showed promise to treat multidrug resistant bacteria.

But it was patented, access was limited, and cost was high.

“It seemed so unfair to millions of others,” Tisile said.

She began working with the South African group, TB Proof, as an advocacy officer in Cape Town. “I realised if there’s no advocacy or voices from the community, nothing will be done,” she told Scroll.

Through conferences and meet-ups, she built a network beyond South Africa.

At one such meeting, she met Nandita Venkatesan, an Indian who, like her, had survived tuberculosis but lost her hearing ability.

In 2019, the two women filed an application with the Controller of Patents office in Mumbai opposing a secondary patent grant to Janssen Pharmaceutica, the manufacturer of the bedaquiline drug. No application was filed in South Africa, where the medicine is under a patent at least till 2029.

Six years before them, a patient group called the Network of Maharashtra People Living with HIV had filed a similar application opposing Janssen’s patent. The human immunodeficiency virus, or HIV, damages the immunity of those who contract it, making them highly vulnerable to tuberculosis. Prohibitive costs of tuberculosis medicines are a challenge for HIV positive patients, too.

“It is easier for HIV positive people to acquire tuberculosis infection and die of it, because our immunity is lower than normal population,” said Shabana Patel, from the Network of Maharashtra People Living with HIV.

With this patent grant, Janssen would have held monopoly rights over the production of bedaquiline till 2027. A patent allows exclusive rights to the inventor and prevents others from making and selling the drug.

What Janssen was trying to pull off is called evergreening of patents, where big pharmaceutical companies extend the period of a patent by introducing minor variations in drug formulation.

In March this year, however, the Controller of Patents rejected Janssen’s request for a secondary patent, effectively paving the way for generics to enter the market once the primary patent ends in July 2023.

It was an example of how determined advocacy by patient groups, with the help of legal aid organisations, can stop big pharmaceutical companies from profiting from life-saving medicines – even at the expense of patients.

How it started

“The genesis of challenging patents lies in the AIDS movement,” said Leena Menghaney, South Asia regional head of Médecins Sans Frontières. “It first began in Thailand in 2001 to remove patent rights from a drug used for HIV treatment called didanosine. Then, in South Africa, people began challenging patents for HIV medicines at the turn of the century.”

In India, too, HIV support groups and patients have been at the forefront of opposing patents of some crucial medicines.

Among them is 45-year-old Patel, who was diagnosed with HIV in 1998.

In 2000, she and six other HIV infected people decided to start a network to support patients and battle social stigma against HIV. “We started the Network of Maharashtra People Living with HIV,” said Patel. “We wanted to bring a human face to represent the HIV movement.”

She soon realised that their fight went beyond a demand for social equality. “Right to live is an essential right. If we don’t get medicines, how will we survive?” she said.

Several medicines, which could save the lives of HIV patients, were patented and highly priced at the time.

Patel came in contact with Anand Grover, a senior lawyer who heads the Lawyer’s Collective, a legal aid organisation that works for patient rights. The collective began educating Patel and activists like her about laws related to patenting drugs.

Grover said the 1995 World Trade Organization’s Trade-Related Aspects of Intellectual Property Rights agreement or TRIPS, made it necessary for member countries to allow patents for any invention. Although India put up a resistance, it eventually became one of the final signatories.

“Around 2000, India realised that the patent law would have to be modified due to the TRIPS agreement,” Grover said.

In 2005, India passed an amendment to its Patents Act of 1970, allowing a patent to be filed for a product or a process.

A crucial Section 3(d) was introduced, which stated that a patent will not be granted for merely introducing a new substance unless it can prove advanced efficacy. “That amendment is crucial, for it gave a platform to file an appeal against a patent,” Grover said.

The Indian Patents Act allows for any person or group to oppose a patent application before it is granted.

Initially, Grover said, Indian manufacturers opposed patent applications when they saw the lucrative business in generics.

Later, when global pharmaceutical companies began allowing the generics companies to produce drugs under voluntary licence agreements, they stopped opposing patents. “The only people who could challenge the patents were from civil society,” said Grover.

In 2006, the Madras patent office rejected Novartis’s application to patent Gleevec, a cancer drug to treat leukemia – the first case of patent rejection after the 2005 amendment.

The patent had been opposed by the Cancer Patients AIDS Association and Section 3(d) formed the basis of the rejection.

The case went up to the Supreme Court, which in 2013 rejected the patent request.

The Novartis case gave a boost to patient groups, Patel said. “We began filing patent opposition against expensive HIV medicines,” she said.

In 2011, the Indian Patent Office also rejected pharmaceutical giant Abbott’s request for a patent on the combination of antiretroviral drugs, lopinavir and ritonavir, both used to treat HIV.

The fight for cheaper bedaquiline

Before bedaquiline got its present name, it was labelled as the TMC 207 compound. A Belgium company, Janssen Pharmaceutica, was the first to discover the compound in 2002 and began researching it. In India, the patent application was published in 2005. The patent would last till July 2023.

In December 2012, the United States Food and Drug Administration granted bedaquiline an accelerated approval to treat multidrug-resistant tuberculosis. Soon, word about bedaquiline and its increased efficiency in treating tuberculosis, began circulating in patient groups. But accessing it was a major challenge.

Three years ago, Janssen had applied for a secondary patent in India, this time for the fumarate salt of the base compound TMC 207. The same year, Johnson and Johnson took over Janssen.

By then, in countries with a high tuberculosis burden, Médecins Sans Frontières began to educate civil society activists about the technical details of the fumarate salt, how it was being used to file another patent and how that would defeat all efforts to make the drug more accessible to the majority of tuberculosis patients.

“Knowing that the company would try to evergreen its patent, we had started collecting data on patent registration applications across countries,” said Menghaney of Médecins Sans Frontières.

In 2012, the year the United States Food and Drug Administration approved bedaquiline, tuberculosis had killed 1.3 million people globally. Of those, 1,87,000 had HIV. India accounted for 26% of the total tuberculosis deaths, a World Health Organization report said.

“Bedaquiline was now all the more important to save lives,” Patel said.

But the drug was not part of medicines given for free under the government’s tuberculosis programme, and was not easily available to purchase. Only a few doctors were able to procure it on compassionate grounds on a case-by-case basis. “It was crucial that generic versions were introduced,” Patel said.

In 2013, the Network of Maharashtra People Living with HIV filed an application opposing Janssen’s application to get a secondary patent for the fumarate salt.

The long wait

Grover said in the last decade patient groups have become active enough to follow up patents on their own. In the case of bedaquiline, though, there was silence on the part of the Controller of Patents.

In 2018, the World Health Organization changed tuberculosis treatment guidelines, and recommended countries replace injectable drugs with bedaquiline, which helped shorten the time needed for treatment and had a higher success rate of curing the infection.

“That got me thinking, that this will be an important drug for the future,” said 33-year old Nandita Venkatesan, currently a data journalist with Mint.

She said India needed a shorter regimen and it had to do away with injectables, which are drugs administered intravenously. Apart from pain from repeated injections, the drugs can also cause severe effects such as hearing loss and kidney damage.

“Although bedaquiline has its own share of side-effects, it was better than the injectables,” she said.

Venkatesan, now cured of tuberculosis, said she had no personal stake in the patent opposition application. “It seemed like the right move for patients,” she said,

With Tisile, she filed a second pre-grant opposition in 2019 to push harder for access to bedaquiline.

Then Covid-19 hit, and for two years again, the patent office was silent.

In November 2022, it began online hearings. The patients’ group argued that the fumarate salt provided no greater therapeutic efficacy over the base compound and a secondary patent had no merit.

In March this year, the patent office rejected Janssen’s application.

The impact

The decision is expected to reduce the cost of bedaquiline treatment by half. Currently, it costs around Rs 22,000 for a six-month course. “Just bedaquiline accounts for 50% to 70% of the treatment regimen cost,” said Menghaney from Médecins Sans Frontières.

Drug makers Macleods Pharmaceuticals Ltd and Lupin Limited have already applied for pre-qualification in the World Health Organization for their generic versions, Menghaney said. Pre-qualification is a process where the World Health Organization labels or certifies a pharmaceutical product to be of standard quality.

India’s HIV positive patients, too, have benefited when patents have been rejected.

Ganesh Acharya, an HIV positive activist, said the cost of the combination of lopinavir and ritonavir, important to control the HIV infection, was priced Rs 12,000 for a month’s course when Abbott had exclusive rights for production.

Once its patent was rejected, many manufacturers brought out generic versions. “Now the cost is Rs 3,400 or so for a month’s course,” Acharya said. “For a poor person, this is not very affordable, but at least it is not completely out of reach.”

Although India provides free antiretroviral medicines for HIV patients, every few months, government centres suffer a stock-out, forcing patients to buy medicines.

An HIV positive person able to continue medication has a greater chance of increasing their immunity against other diseases. Someone who drops out of treatment becomes vulnerable to other infections. In Acharya’s case, he suffered from tuberculosis twice.

“That is why it is so important for life-saving drugs to be cheaper and more accessible to the poor,” said Acharya.

This reporting was supported by a grant from the Thakur Family Foundation. Thakur Family Foundation has not exercised any editorial control over the contents of this article.