The problem with drug discovery
An expert in the field believes that the way we are developing new drugs is inefficient and flawed.
The development of new drugs is an extremely expensive endeavour with a very high failure rate.
MOST of us tend to take modern medicines for granted. We have faith that there is a drug or procedure out there that will be able to treat and/or cure whatever ailment we have.
And while there is certainly a large number of approved medicines out there in the market, there are still many diseases that don’t have a cure or treatment.
There are also drugs that are becoming less effective, like antibiotics certain bacteria have become resistant to.
Developing a new drug is a very expensive endeavour, with a very high failure rate.
Said University of Oxford Nuffield Department of Clinical Medicine professor of translational medicine Dr Chas Bountra: “I’m interested in trying to discover new medicines.
“I believe the way we are currently doing it is incredibly inefficient.”
He explained: “I believe it is too costly, it is too risky and it is too slow.”
Quoting a 2014 Forbes analysis, Prof Bountra noted that the average cost to develop a new drug that makes it to the market for Amgen was US$3.5bil (RM14.1bil), which he said was unsustainable.
And Amgen was the best performer in the study; AstraZeneca, for example, spent an average of US$11.5bil (RM46.3bil) per new drug.
“And many of these drugs were not completely new drugs. They were what we call ‘me toos’ or new formulations; they were a variant of an existing drug.
“And what we need is more novel drugs,” he said.
The fact is, very few compounds make it all the way to a full-fledged safe and effective drug for humans.
According to the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA), a total of 56 medicines were launched in 2015, while there are currently more than 7,000 compounds in development worldwide.
Looking specifically at cancer drugs, Prof Bountra noted that a 2015 study reported that there were 529 molecules targeting cancer in development in 2002.
A decade later, 45 had made it to the market, 95 were still in development and 389 molecules were terminated.
“So we took 389 molecules into the clinic, into phase 1, 2 or 3 studies (clinical trials), and terminated them.
“Imagine how much money we spent on those 389 molecules.
“Imagine how many people’s careers went into that.
“But most important, imagine how many patients were exposed to those 389 molecules, and then they were terminated,” he said.
The same study also calculated that only 7.5%, or less than one in 10, of molecules targeting cancer in phase 1 clinical trials made it to the market.
Even those molecules that made it to the final phase 3 clinical trial stage only had a 33%, or one in three, chance of making it to the market.
Meanwhile, the IFPMMA Facts andd Figures 2017 report stated that 9.6% – still less than onne in 10 – of all drugs in developmeent make it to the market from phasee 1 clinical trials.
Meanwhile, only halff, or one in two, drugs in phase 3 clinicalc trials make it to the market.
“This process is too rrisky,” said Prof Bountra.
He shared that an analysis done by his Oxford colleagues three years ago showed that it took between six to 30 years for a molecule targeting cancer to make it into phase 1 clinical trials from the time of its discovery in the lab.
According to the IFPMA, it takes an average of 10 to 15 years to develop a new drug from the time of discovery in the lab to the market.
“This is too slow,” he said.
What patients want
Speaking at the 2nd CambridgeOxford-Sunway Biomedical Symposium held at Sunway University in Selangor recently, Prof Bountra said: “We need to think about our customers and our stakeholders.
“And the customers in drug discovery, of course, are our patients.
“And the various stakeholders could be academic collaborators, it could be collaborators in industry, iti could ld b be patient i organisations, i i it i could be governments, it could be regulatory agencies, it could be the payers of those medicines, etc.”
He opined that patients, their families and caregivers, as well as society, want novel, effective and affordable medicines quickly.
According to the research and expert opinions Prof Bountra quoted, there has been no new drug for Alzheimer’s disease since 2002, nor has there been a truly novel antibiotic since 1984 or psychiatric drug for the last three or four decades.
“In 2014, 44 drugs were approved by the FDA (the US Food and Drug Administration); 39% of those were novel.
“In 2015, 51 drugs were approved by the FDA, and coincidentally again, only 39% were novel,” he said, adding that in 2015, 86% of prescriptions were for generic drugs.
He also shared that a 2014 analysis had looked at the then 71 drugs available to treat solid tumours and how much they had increased progression-free survival for the patients who had such cancers.
The answer was two-and-a-half months on average.
Progression-free survival is the amount of time during and after treatment that a patient lives without the cancer getting worse. It is usually used to measure how well a cancer treatment works.
Meanwhile, the overall increase in survival was, on average,
2.1 months.
“And of these 71 drugs, they concluded that only 30 had clinically meaningful efficacy,” he said.
He noted that the need for more affordable drugs is increasingly becoming a global issue.
He shared an analysis done in the United Kingdom on cancer drugs in the years 2000 and 2013.
In 2000, there were 698 cancer drugs available, with an average of 181 days of treatment, and an average cost of £3,000 (RM16,420) or 20% of the GDP per capita.
In 2013, there was an additional 63 drugs available for a total of 761 cancer drugs, with an average of 263 days of treatment, and an average cost of £35,000 (RM191,568) or 140% of the GDP per capita.
“And that trend is continuing,” he said.
GDP per capita is a country’s gross domestic product divided by its population, and is used to measure a country’s standard of living.
As for needing new drugs quickly, Prof Bountra commented that “of course, for patients, even tomorrow isi too l late”.
How does it work?
“This industry employys some of the smartest peeople on the planet; they have access to any techh- nology they want, they