The fight against life-threatening infections suffered another blow when one of the world’s biggest drug makers waved the white flag. Business Day reports that Novartis has announced that it is ending antibacterial and antiviral research to "prioritise resources". That comes after GlaxoSmithKline (Glaxo) put some antibiotics assets under review, Medicines Co sold its business and Sanofi shifted its portfolio to Evotec. Allergan said in May that it would leave the field and AstraZeneca, once a leader, washed its hands of antibiotics two years ago.
The report says the pullback revives concern about a world in which routine infections again become lethal as bugs develop resistance to existing drugs. Sales of new antibiotics are too low for big pharma to recoup its investments, and public measures to encourage more activity aren’t moving the needle.
"The market is broken," said David Shlaes, a former pharmaceutical executive and consultant. "We’re at a point now where resistance is moving a lot faster than our ability to provide new antibiotics. This is just another in a long string of really bad news."
The report says the latest retreat comes after a brief period when industry leaders appeared willing to take a risk on the field. Merck spent $8.4bn on antibiotics leader Cubist in 2014. Novartis, Glaxo and other companies pledged at the World Economic Forum in 2016 to fight the threat of drug-resistant bacteria. The US government offered longer patent protection and subsidies, potentially worth hundreds of millions of dollars, to companies willing to invest.
But, the report says, the new antibiotics just have not sold. Only five of the 16 brand-name antimicrobials approved from 2000 to the end of 2017 were able to generate sales of more than $100m annually, according to a study from Duke University’s Margolis Centre for Health Policy. That is a pittance compared with the billions of dollars for new cancer treatments.
The problem for drug makers is that new antibiotics are usually held in reserve and are not used unless they are needed because patients develop resistance to an older medicine. Even the most expensive antibiotics, at about $1,000 a day, are cheap compared with a cancer medicine that will be given for months instead of a few days or weeks.
Meanwhile, developing new antibiotics is becoming more expensive, Gabrielle Breugelmans, director of research for the Access to Medicine Foundation is quoted in the report as saying. The roughly 275 research projects going on around the world might yield two or three medicines, she said. "Novartis pulling out makes us a little worried, because they had a relatively large pipeline" of new antibiotics, Breugelmans said. "Now it is not clear what will happen."
Novartis said it would look for partners for its experimental drugs. If it follows recent precedent, it may wind up handing its assets to a much smaller company. As other drug makers have exited antibiotics, they’ve hived off their assets to biotechs willing to assume a higher risk.
Medicines Co sold its portfolio to Melinta Therapeutics, while AstraZeneca spun out its research to a standalone company called Entasis Therapeutics before selling the rest of its antibiotics unit to Pfizer.
"Anti-infectives in the blockbuster race of Big Pharma don’t make sense," said Werner Lanthaler, CEO of Germany’s Evotec, which took over Sanofi’s portfolio in 2018. "In the commercial model of Evotec, a €200m product that you co-develop with someone can make sense." No one can make a business case for antibiotics without long-term public support, Lanthaler said.
Faced with the prospect of drug-resistant bacteria killing 10m people a year by 2050, according to a UK report, governments are considering more aid. The report says in the US, Congress is considering legislation that proposes an exclusivity voucher for companies that develop badly needed new antibiotics – a voucher that can be transferred to another product or sold. And in India, where superbugs kill nearly 60,000 new-borns every year, the government has provided early research funding to homegrown start-ups including Bugworks Research India.
"We think the tide may be turning from a scientific, as well as a regulatory and pricing, perspective," said Kasim Kutay, CEO of Novo Holdings in Denmark, which launched a $165m fund in February to combat antimicrobial resistance. The fund has received more than 50 investment proposals from Europe and will probably make its first investment by the end of 2018, Kutay said.
The report says Merck, the US drug maker that bought Cubist, said it had committed to its antimicrobial research. So did Roche, the Swiss cancer specialist, which also has a pipeline of antibiotics. Glaxo, the biggest player in the field, said in 2017 that it would carry out a review of its cephalosporins antibiotics business and might look at selling the operations. The company says it had an experimental antibiotic in late-stage development and there was a need for "creative ways to incentivise and reward new research and development in antibiotics".
The departure of some big drug-makers such as Novartis "hopefully is going to add pressure to find ways to correct some market failings," said Graham Lumsden, CEO of Motif Bio, whose experimental antibiotic Iclaprim is under regulatory review in the US "This is where the biotechs have to pick up the slack."
[link url="https://www.businesslive.co.za/bd/companies/2018-07-13-big-pharma-is-leaving-the-field-of-antibiotic-research-in-droves/"]Business Day report[/link]