Drug development: Teaching old pills new tricks

Exploding research costs and falling sales: there seems to be no cure for the pharma industry’s two big afflictions. But it may have found a way to both cut costs and open up new markets: repurposing drugs already approved for treatment of one disease or those that failed to gain approval in the late stages of development. Alas, this is not as easy as it sounds—mostly for legal reasons.

Finding new uses for old or failed drugs is on average 40% cheaper than inventing a new drug from scratch: it allows to skip the early stages of development. Since coming up with a new drug can cost more than $1 billion, such savings are nothing to sneeze at. Repurposing also trims the risk of failure because new drugs hit a dead end mostly during the early stages of development.

In 2007, a report in Nature, a science journal, counted 41 drugs that have found new uses. But there should be many more, experts say. This is why America’s National Institutes of Health, the country’s biggest government agency financing drug research, and the Medical Research Council, its British counterpart, each have launched new grant programmes. Worth $20m and £10m ($15m) respectively, they are meant to allow university researchers analyse failed drugs from big pharma firms such as Pfizer, AstraZeneca and Eli Lilly and see whether they can be repurposed.

Yet such schemes are not enough, as work by Grant Churchill, a researcher at Oxford University, shows. In a recent paper in Nature Communications, another science journal, he describes how he and his colleagues looked for a drug to treat bipolar disorder, which causes uncontrollable mood swings. Instead of developing a new compound, they tested a library of known ones and found that ebselen, a drug first developed to treat stroke, was a candidate. Their claim, based on animal tests, is that ebselen is as good as and much safer than lithium, currently considered the best treatment for bipolar disorder.

But this was where things hit a hurdle that is hard to overcome. Universities do not have the money to further develop promising drug candidates that need to be tested on a large scale. Expensive human trials are usually carried out by pharma firms, which own the patent for a drug and thus can hope to make their money back. But in the case of many repurposed drugs, like ebselen, the patent has expired. Filing for a new one, which is possible, is not of much help: patients could simply buy versions of the drug which are already available from other makers.

One way of solving this problem would be to change the patent system, for instance by extending the length of patent protection, but this could hamper innovation in other ways. A better solution, argues Benjamin Roin, a law professor at Harvard University, is to have regulators grant the drugmaker that has repurposed the drug some exclusivity and thus time to recover research costs: it is rare that a drug is used in the same form and the same dosage for two different diseases; regulators could wait a few years before they allow other firms to offer the drug for the new purpose. If old drugs can learn new tricks, regulators should do so, too.

First published on economist.com.


  1. Singh et al., A safe lithium mimetic for bipolar disorder, Nature Communications2013.
  2. DiMasi et al., The price of innovation: new estimates of drug development costs, Journal of Health Education2003.
  3. Chong & Sullivan, New uses for old drugs, Nature2007.
  4. Roin, Unpatentable Drugs and the Standards of Patentability, Texas Law Review2009.

Image credit: The Economist

Cancer drugs: Refusing to die

Suicide is a part of life. Whenever any of the 100 trillion or so cells that make up the human body malfunction, which happens all the time even in healthy tissue, they are programmed to provoke their own death. The mechanism hinges on a protein called TRAIL, which is produced by the damaged cell and binds to receptors on its surface, causing inflammation. That is a signal for the immune system to sweep in and, through a process called apoptosis, break down the damaged cell and recycle its parts to feed healthy ones. If this self-destruct is subverted, however, the result is a tumour.

When TRAIL’s tumour-suppressing ability was first discovered in 1995 researchers hoped that by discriminating between cancer cells and healthy ones, TRAIL would do away with the debilitating side-effects associated with traditional treatments like radio- and chemotherapy. These are good at destroying tumours but also cause lots of collateral damage. Unfortunately, it turned out that simply injecting a synthetic version of the molecule into the patient’s body provoked only a limited immune response in a handful of cancers.

That, says Joshua Allen from the Pennsylvania State Cancer Institute, was because people assumed that cancer’s subversion of TRAIL consisted merely in halting the molecule’s production within the cell. It turns out, however, that cancerous cells also suppress their TRAIL receptors, so no amount of synthetic TRAIL sloshing about would ever be enough. What you need, Dr Allen reasoned, is something to reboot the TRAIL-producing pathway within cells as well as to unblock their TRAIL receptors. Only then would the immune system be spurred into action.

So he and his colleagues sifted through a library of molecules maintained by America’s National Cancer Institute and found a molecule, called TIC10, whose biochemistry seemed to fit the bill. When enough of these molecules accumulate in a cancer cell, they activate a protein called FOXO3a. This binds to DNA and flips on many biological pathways, including those involved in the TRAIL mechanism that lead to the immune-system alerting inflammation.

As Dr Allen and his colleagues report in Science Translational Medicine, tests in mice with brain tumours confirmed the biochemical hunch. Murine subject given TIC10 lived twice as long as those that received no treatment. The drug also worked for lymphoma, as well as breast, colon and lung cancers. And it did not seem to cause the wasting side-effects typically associated with chemotherapy, suggesting that it can indeed tell cancer cells from healthy ones. As an added bonus, TIC10 is small compared to TRAIL, and cheaper to concoct than the complex protein is.

Last year Dr Allen secured a $1.3m grant from Pennsylvania’s department of health to begin clinical trials. These will be carried out in collaboration with Oncoceutics, a drug company. Nine out of ten promising molecules which work in mice fail in humans, so “Cure for cancer” headlines must wait. If TIC10 does live up to its promise, though, it would make one killer app.

First published on economist.com.

Image from here

A nebulous future

Before Apple launched iCloud in 2011, Steve Jobs allegedly offered to buy Dropbox, a file-sharing service founded in 2007, for $800m. When Dropbox declined, Apple’s late boss disparaged it as a feature, not a company. Soon after, Dropbox raised $250m, putting its value at over $4 billion. Earlier in December Dropbox concluded a promotional campaign that, in just a few weeks, added 2m new users, bringing the total to over 100m, roughly double the number when Jobs made his comment. Consumers, it seems, can’t get enough of the feature.

Dropbox dominates online file-sharing. It boast three times as many users as its closest direct rival, YouSendIt. (Its dominance is even more pronounced when it comes to the volume of data stored.) It eats up 20% of all bandwidth consumed globally by browser-based file-sharing services, against 1% for YouSendIt. Dropbox users save more than 1 billion files every day.

Most of them use the free version of the service. The company makes money by charging for extra storage. Around 4% of users plump for the premium version, though the proportion is growing, according to Arash Ferdowsi, one of the Dropbox’s co-founders. The recent campaign, called Space Race, gave away free space to university students in return for getting their peers to sign up to the service. The hope is that when access to this extra storage runs out after two years, the students, by then freshly-minted professionals, will pay to keep using it.

Dropbox relies on individuals and small firms, for whom its rudimentary security features are good enough; bigger businesses with sensitive information prefer more secure services like Box.net. The advent of competitors in the nebulous form of iCloud, Google’s Drive and Microsoft’s Skydrive, which come pre-installed on their respective makers’ gadgets, does not seem to have dampened enthusiasm for Dropbox. Unlike iCloud, which boasted 190m users by October thanks to its deep integration with Apple’s mobile devices, the service is “platform neutral”—ie, works across different devices and operating systems—and allows easy file-sharing, both useful traits in an increasingly connected world where few people hew devoutly to a single device-maker.

Google and Microsoft clouds emulate Dropbox in these respects. But at a little over 10m users each, they do not yet benefit from from the incumbent’s powerful network effect. If you are sharing files with a dozen other people on Dropbox, a move to Google or Microsoft would require all 12 to move with you.

Dropbox is also striving to make itself the default choice for smartphone users. In 2011 it struck a deal with HTC, a Taiwanese phonemaker, to preinstall Dropbox on its Android devices. In return it gives HTC users 5GB of space for free. HTC has been struggling of late, but Mr Ferdowsi says that his company is in talks with other manufacturers, hoping for similar arrangements.

A bigger long-term worry is the plummeting price of digital storage. With its vast scale, Amazon has driven down costs substantially for the likes of Dropbox, which leases server space from the e-commerce giant. But Google Drive already offers 100GB for $5 a month, half what Dropbox charges for the same amount of storage. And Google can advertise its cloud across its myriad online offerings. Dropbox’s margins are only likely to get wispier in the future.

First published on economist.com.

Image credit: Dropbox