The company’s attempt to extend its patent of a critical tuberculosis drug has left millions of patients unprotected. Indians, however, are not among them thanks to our country’s sturdy patent laws. We explain how ‘evergreening’ works—and how it profits companies like J&J at the expense of human lives.
Researched by: Nirmal Bhansali & Aarthi Ramnath
A quick reminder about TB
Tuberculosis is the world’s most lethal infectious disease. In 2021, 10.6 million contracted TB—and 1.6 million died of the disease. Eight countries account for more than two thirds of global TB cases—with India (26%) leading the pack. China comes in a distant second at 8.5%. FYI: TB is a bacterial infection that spreads through the air.
Drug resistant TB: The disease is treatable and curable. The real challenge is multidrug-resistant tuberculosis aka MDR-TB. Between the 1940s and 1960s, eight drugs were developed to treat tuberculosis. However, people often do not take the proper course of the prescribed antibiotics—due to ignorance or more often lack of access. As a result, the bacteria has become resistant to two of the most potent TB drugs:
The Lancet found that almost 44% of patients with TB in countries like Russia, Peru and Thailand showed resistance to at least one second-line drug, or that a medicine used after another drug had already failed. Treating drug-resistant TB can take years and can cost 200 times as much as treating the ordinary form of the disease.
As TB cases receded in rich countries, there was very little incentive for pharmaceutical companies in the West to develop new drugs. That’s until Johnson & Johnson rolled out Bedaquiline in 2012. And it soon became a critical component in treatments for MDR-TB. Most importantly, it was safer than other TB drugs:
The drug is considered a gamechanger because previous treatment involved up to two years of painful injections, which not only caused side-effects such as hearing loss, but had a high death rate.
But, but, but: The price of this ‘gamechanger’ is steep: $1.50 per day (or $272 over the six-month treatment regimen). That’s why Bedaquiline remains unavailable in many countries. It accounts for 70% of the cost when used in a drug cocktail. The estimated price for a generic equivalent would be much cheaper:
Doctors Without Borders has argued that “with scale-up and generic competition, the price of bedaquiline would be expected to drop, bringing it closer to its target price of $0.50 per day,” a price at which bedaquiline would still be profitable for manufacturers. This almost 67% reduction in price would dramatically increase the availability of bedaquiline.
The evergreening of Bedaquiline
Reminder re patents: Most patents for new drugs last for about 20 years. A primary patent gives the company time to recoup the costs spent in researching and developing the medicine. And once the patent expires, other companies can begin manufacturing generic versions—driving the price of the drug down. This is how patents ought to work.
Enter evergreening: Companies, however, try and extend the life of their patent by applying for “secondary patents.” They create minor variants of the drug—claim it represents a brand new innovation. This is called ‘evergreening’—and is aimed at preventing the entry of cheaper generics into the market.
The Bedaquiline manoeuvre: J&J’s patent was set to expire in July. But the company had already applied for secondary patents—and planned to enforce them in 30 lower or middle income markets to protect its profits. It would have extended J&J’s control over the medicine for at least four more years.
The drug would still cost at least $45 per month—a total of $270 for the required six month treatment. J&J’s defence:
J&J has defended its secondary patents by arguing that the profits it makes are vital for developing innovative medicines to eradicate diseases such as TB. In contrast, “Generic manufacturers ... do not typically reinvest in the development of new medicines,” J&J said in a statement to the medical news service MedPage Today.
Big point to note: The research and trials for Bedaquiline were mostly financed by the US government and NGOs—which put in anywhere between $455 to $747 million in direct and indirect financing.
India just says ‘No’
J&J unsurprisingly applied for a secondary patent in India—which has the most TB cases in the world. However, its application was rejected in March. That’s because India has a strict criteria for assessing secondary patents—and it dates back to 1970:
Section 3(d) of The Patents Act, 1970 in India was an innovation in its own right, albeit one in law, which deals specifically with such inventions. The statute clearly defines the standard for follow-on patents on drugs as one of therapeutic efficacy, where applicants may need to supply some clinical evidence. This standard was tested and upheld by the Supreme Court in a landmark decision in 2013 involving a patent application for Novartis’ anti-cancer drug Glivec.
The India Patent Office delivered its judgement in response to a plea filed by two tuberculosis survivors—Nandita Venkatesan and Phumeza Tisile from South Africa.
The J&J claim: was that it had added two novel ingredients to Bedaquiline: a fumerate salt and a wetting agent. Turns out neither additions were innovative—nor did they improve the effectiveness of the drug:
Ms. Venkatesan and her team provided evidence that the preparation of water-soluble compounds through salt formation, which is used to prepare the drug Bedaquiline, has long been known to pharmaceutical manufacturer and is even cited in chapters of Remington’s Pharmaceutical Sciences and other common textbooks on the subject.
As a result, two major Indian manufacturers are already making generic versions of the drug. And the move laid the ground for a historic deal struck by J&J in the following months.
A historic deal: In July—right when J&J’s patent was set to expire—it inked a deal with the Global Drug Facility (GDF)—a non-profit supplier that negotiates bulk purchase of TB medicines on behalf of lower and middle income countries. The company agreed to supply 44 countries with Bedaquiline at a far lower price of $130. And it also agreed to give them access to generic alternatives from Indian companies. The agreement was unprecedented:
While companies sometimes negotiate licenses with a few individual general suppliers, it’s unprecedented for a major pharmaceutical corporation to partner with a nonprofit global supplier such as GDF. In late July, GDF called generic manufacturers to bid on supplying bedaquiline.
While GDF says J&J was not influenced by India’s rejection of J&J’s secondary patent, others disagree:
But others suspect the patent setback in India was an important turning point for the pharmaceutical giant, which declined comment for this article. The loss in India “has broken down J&J’s resistance in allowing generic supply,” argues Leena Menghaney, a lawyer who is global intellectual property adviser with MSF in New Delhi and who offered technical support on the Indian patent challenge. “I think it has played a tremendous role in changing J&J’s mind about licensing the drug.”
But, but, but: The agreement left many other countries in the lurch. For example, 17 countries—including Russia—will not get access to generic versions because J&J has inked a separate deal with a Russian pharma company that controls these markets. Others like South Africa and Indonesia are not part of the GDF alliance. And many of these countries have a high number of TB cases.
Most importantly: It left intact the secondary patents filed by the company—which made many activists unhappy:
“We remain concerned that J&J retains the global authority to determine access to lifesaving generic versions of bedaquiline in countries with a high burden of TB, even after the expiration of the main patent,” said Christophe Perrin… Perrin said the company should not enforce its existing secondary patents and withdraw any pending applications for more. If it does not, governments should override the patents and seek to buy the drug from generic manufacturers.
And that’s exactly what South Africa now plans to do. Its Competition Commission will investigate J&J of charging excessive prices for bedaquiline—and excluding competition from generic drug makers. TB is the leading cause of death in South Africa.
The bottomline: India’s generic drug industry is hardly perfect—neither is the application of our patent laws. As this Hindustan Times column points out, there are serious quality issues with generics sold in India—as opposed to those exported to richer countries. But we are doing far better than many parts of the world—as South Africa or Russia would testify.
Scientific American, Science and TIME are best on the deal between J&J and GDF. Washington Post explains why access to bedaquiline is critical. Two good reads in Mint: This column by Feroz Ali and Sudarsan Rajagopal on India’s patent laws and this piece penned by Nandita Venkatesan and Priyam Lizmary Cherian—the petitioners who spearheaded the campaign against J&J in India. The Hindu has more on why its application was rejected