Evergreening

On 18 July 2003, Johnson & Johnson filed a patent for bedaquiline, a new antibiotic against Mycobacterium tuberculosis. If and when it was approved as a medicine, J&J would hold the exclusive rights to manufacture and sell bedaquiline across the world until 18 July 2023. After that, other companies would be allowed to make generic versions of the drug.

The patent became public in February 2004, and the astonishing activity of bedaquiline was reported in Science in early 2005. Researchers in Belgium led by Koen Andries showed that the compound was effective in the test tube and in mice – killing an order of magnitude more bacteria than previous TB drugs. Andries – not one of the chemists listed as the inventors on the patent application – said it was ‘like a dream come true’ for his team: ‘What drives us most is the medical need for such compounds.’

In December 2007 J&J filed a secondary patent on bedaquiline fumarate, the ‘pharmaceutically acceptable’ form of bedaquiline that’s given as a medicine. It can be made by adding fumaric acid to bedaquiline; a standard chemical manouevre used for many drugs. At first glance, this is strange. J&J’s original patent had already made sure to claim exclusivity not only over bedaquiline but over its pharmaceutically acceptable forms as well, and had listed fumaric acid as an example of what could be added.

The secondary patents were an attempt to extend the exclusivity on bedaquiline beyond the so-called ‘patent cliff’ of 18 July 2023, allowing J&J to control the global supply and price of the drug for another four years, a process known as ‘evergreening’.

Predicting the economic potential of a medicine is an old problem for capitalism. ‘If we speak frankly,’ John Maynard Keynes wrote in his General Theory, ‘we have to admit that our basis of knowledge for estimating the yield ten years hence of a railway, a copper mine, a textile factory, the goodwill of a patent medicine, an Atlantic liner, a building in the City of London amounts to little and sometimes to nothing.’

J&J came close to cancelling their whole bedaquiline research programme. Andries has said that after initial trials in 2006 went poorly, ‘management gave us the chance to do one last clinical trial with the drug. If it didn’t work out, they would pull the plug.’ When the statistician showed him the results of the next trial, though, Andries saw immediately that ‘we had hit the bullseye.’

TB is preventable and usually curable with a cocktail of four drugs, but around 1.6 million people die from it every year, largely because of a lack of access to treatment. Another growing problem is drug-resistant forms of the bacteria, which undermine the cheap standard treatment and can only be treated with increasingly toxic and painful injections. Bedaquiline, which could be given orally and for a much shorter time, was a revolution.

It was first approved as a medicine in the US in 2012 and is now listed as an essential medicine by the WHO. What should a fair price be for an essential drug? J&J sell bedaquiline at tiered prices around the world: it is more expensive (but easily available) in wealthy countries and cheaper (but hard to come by) where it is most needed. According to Médecins Sans Frontières, in late 2022 it was nearly three times as expensive as it would be in low-income countries if generic forms were available.

India has around 130,000 drug-resistant TB cases a year, but according to the British Medical Journal only ten thousand people have so far received bedaquiline in the eight years it has been licensed for use in the country. Activists and TB survivors lodged oppositions with the Indian Patent Office to the bedaquiline fumarate patent, arguing that it didn’t represent genuine innovation. The IPO decided in their favour in March, which meant that on Tuesday, after twenty years, bedaquiline became a generic drug in India.

The patchwork and messy nature of patent law means, however, that J&J still hold the secondary patents in many countries. Last week, the American writer John Green accused J&J of ‘denying access to bedaquiline to around six million people’ and pursuing a ‘bad business model’. Green encouraged his online community to call on J&J to renounce their patents. A few days later, J&J announced a partnership with the non-profit Global Drug Facility, a negotiating block for generic manufacturers. The details are limited, but under the deal J&J will permit generic versions of bedaquiline to be manufactured in countries with a high TB burden.

Campaigners have welcomed the news but highlighted how the deal falls short: J&J could have renounced their secondary patents altogether. The Treatment Action Group, an HIV/Aids organisation, has called the deal ‘a creative procurement solution’ that does something for the access crisis ‘without solving the larger structural injustices’. There are also notable gaps in the deal. It could have been universal, but instead J&J have chosen to not include some countries (in Eastern Europe, for example) where drug-resistant TB is common.

The big pharmaceutical companies always claim that patent rights are the mechanism to fund new medicines. It’s true that companies develop new drugs because they have an expectation of reaping future profits – though they are always tight-lipped about the precise costs of their research. But it’s also true, as research by the Treatment Action Group shows, that the amount of public money spent on the development of bedaquiline, depending on how you calculate it, was between 1.6 and 5.1 times J&J’s investment.

Meanwhile, J&J has started the process of suing the Biden administration. The company objects to new legislation that will allow Medicare to negotiate lower prices for widely prescribed but in-patent drugs, including one that J&J sells. The first negotiations are due later this year. According to J&J’s filing, the legislation threatens their fundamental constitutional rights: not only its Fifth Amendment right to private property, but also its First Amendment right to free speech, because J&J will be compelled to make ‘false and misleading statements’ that any resulting price is ‘fair’.