The Superbug is rising: where are the new antibiotics?
Infections kill more than cancer, so why are pharma firms giving up on new researches
LONDON: A ccording to Alan Westwood, chief executive of Matoke, a company hoping to develop a new form of antibiotic, the issue of antibiotic resistance is one of the most troubling issues of our times.
It is one of the biggest threats to human health. In 30 years, it’s estimated 10 million people will die annually from infections impervious to what have been the most powerful weapons in our pharmaceutical arsenal. This is more than the combined number of people dying today from cancer and diabetes.
Superbugs — bacteria which are resistant to all known antibiotics — are evolving fast as uncontrolled sale and misuse of antibiotics are creating resistance rates as high as 20 per cent for some infections.
It is an emerging crisis on a global scale. So you would think that pharmaceutical companies the world over must be racing to find new antibiotics and pouring billions into research.
They’re not.
Research into antibiotics is declining
Most of the giants of Big Pharma have abandoned antibiotics research, ditching these divisions or slashing spending to focus on other, more lucrative areas of science.
In 2016, there were only 200 research scientists developing new antibiotics in the industry, compared with 4,000 working on cancer research, according to professional services firm Pricewaterhouse Coopers (PwC).
Data collated by the British pharmaceutical industry’s trade body shows research spending on drugs to combat infection fell from 7 per ent in 2009 to just 2 per cent less than a decade later. Globally, there are about 50 new antibiotics in clinical development, a tiny number, and of these, only two represent a completely new type.
Just eight big pharmaceutical companies were still conducting research into new antibiotics in 2018, according to the Access to Medicine’s foundation. Since then, two of them, Novartis and Sanofi, have shut down their antibacterial programmes. Only GSK, Pfizer, Merck, Johnson & Johnson, Roche and Shionogi remain.
Why is this area of science so unloved? What can be done to change things before it’s too late?
With the looming superbug crisis, there is a pressing need for new treatments. But what’s also happening is that returns on new antibiotics have been poor over the past 15 years. In many cases, companies haven’t even recouped the cost of developing them.
Why is that? The main reason is simple: new antibiotics do not sell well. Most antibiotics on the market today are effective against most infections and their patents have long since lapsed, so they are cheap [because they are manufactured as generic drugs by a host of smaller companies]. When a new antibiotic is launched, it must therefore prove it is superior to these existing treatments to command a higher price.
We have been through all the low hanging fruit and are now having to be more innovative and find new sources of antibiotics.
On top of this, rising resistance rates have led to a global effort to keep new varieties behind lock and key, for use only when everything else has failed. As a result, sales of new antibiotics have been low.
This might be best for patients, but it’s not so good for drug makers. They are typically reimbursed on the volume of medicine sold.
The lack of investment in the sector also means there has not been a genuinely new class of antibiotic launched in the past 20 years. The ones to hit the market have been variations of existing medications, says Glynn Edwards, chief executive of antibiotics company Summit Therapeutics.
Edwards says health auth-orities would rather stick to cheap generic varieties than pay a premium for an antibiotic which isn’t really that different.
An example of why new antibiotics fail to succeed
Matoke’s Westwood, a veteran of the antibiotics market, having worked in Bayer’s antimicrobial division in the 80s and 90s, illustrates the problem.
“There are five companies that have recently launched antibiotics in the US,” he says. “They were funded from the investment community over the last decade with $2.8 billion (Dh10.3 billion).
“Since then, their share price has on average fallen by 50 per cent and they’ve lost $1.8 billion of the investment money. That was down to weak sales.”
Only 200
Westwood was at Bayer when it developed the broad-spectrum blockbuster antibiotic Ciprofloxacin, one of the world’s most widely prescribed antibiotics. It was launched in 1987 and lost its patent in 2004. It is still on the World Health Organisation’s list of essential medicines.
“We sold a lot. Then in the mid-90s it became difficult, because pricing was coming under pressure and the market was becoming genericised, meaning it was much more difficult to have an impact with a new antibiotic, because in reality, there was nothing truly new coming out.”
Bayer, like many of its rivals, lost its appetite for antibiotic research.
Antibiotics Vs other drugs
For Big Pharma, treatments for chronic diseases, such as hypertension or diabetes, are more lucrative. They are medications that people take every day of their lives, offering a steady income. Successful cancer drugs meanwhile yield hundreds of billions over their lifetime. In the end, pharmaceutical companies have to act in the best interests of their investors.
“The price pressure became intense, antibiotics got squeezed to the point where profitability just was not sustainable. That started to happen in the beginning of the 2000s,” says Westwood.
Big Pharma and governments alike struggle to see value in antibiotics, but for the broader health system they are the most precious of all drugs.
“One thing perhaps people don’t understand is the whole delivery of modern medicine is built on foundation of successful antibiotic drugs,” says Bill Love, chief scientific officer at Destiny Pharma.
“Thanks to antibiotics, you don’t have cancer patients dying of infection, surgical patients dying of infection, children dying from pneumonia. You treat an infection you are cured. If you fix that major pricing element either by carrot or stick, then Big Pharma will definitely come back into this space.”
From Komodo dragons to Iceland: the difficulty in discovering new antibiotics
New varieties of antibiotics have become rare mainly due to the sheer difficulty of discovering them. “We have been through all the low-hanging fruit and are now having to be more innovative and find new sources of antibiotics,” says Seema Patel, head of medical at Pfizer’s hospital medicines division. “Because of this, the way Pfizer goes about drug discovery is not in the same way as it might have been a decade ago.”
10million
Indeed, antibiotics research today is much more collaborative than it used to be, involving academics and researchers and moving away from the lab.
In their search for new cures, scientists are looking further afield: they’re studying Kom-odo dragons to see if a compound in their blood could provide a source for a new antibiotic. They’re examining new species of bacteria in deep thermal vents in Iceland and the antibiotic properties in horseshoe crabs.
Luring back the Big pharma
Steps are being taken to lure the pharmaceuticals industry back into antibiotics. Governments and organisations, such as the Biomedical Advanced Research and Development Authority in the US, The Gates Foundation and the Wellcome Trust now offer generous research grants.
GSK, a British pharmaceutical giant, says these grants have made it possible for the company to continue to carry out research and are holding together a “very fragile industry pipeline”.
Encouragingly, Pfizer moved its antibiotics business from “legacy established products” to “novelty products” this year, which suggests more research could be on the cards.
How UK is leading the change
For all the grant money in the world, pharmaceutical companies won’t pile back into antibiotics unless the economics fundamentally change. Here, the UK is leading the way. The government announced in January that it would change the way it pays for antibiotics this year.
Details of the new pricing structure are vague, but GSK and Pfizer have been helping to develop it. They want to be paid based on the value antibiotics deliver, not how often they are used.
The UK alone can’t solve the antibiotics crisis, but it is the first country to take action. The rest of the G20 club of rich nations have pledged change, but none has made any progress.
“You always need a first mover. So it’s brilliant the UK has stepped forward and recognised it needs to use a different model for antibiotics. If we can show that we can successfully push a couple of products through this new structure, others might follow suit,” says Payne. “Overall, progress globally is good, but it is not fast enough to prevent a superbug outbreak from killing us all.”