17 Nov Researchers Push for Faster Drug Development
As the number of new molecular entities approved by the federal Food and Drug Administration plummets year to year, researchers are scrambling for ways to speed up the laborious drug development process.
Currently it takes about 18 years from the start of target discovery—identifying a certain enzyme or cell or protein one wants to influence—to introduce a new drug to market. The sheer length of that timeline has led pharmaceutical companies and the research firms that contract with them to develop faster and faster methods of high-throughput screening (HTS) and better tools to do it.
One person knee-deep in that battle is Sherri Millis, group leader of assay development for Pierce Biotechnology in Rockford, Ill. Speaking at the 20th Annual Life Science and Venture Conference in Madison recently, Millis noted bluntly that the key is lots and lots of throughput in the lab, which means creating better assays (tools for identifying potential compounds to fight disease).
“The more tools that are available, the more likely pharmaceutical companies will discover drugs,” Millis told a gathering of about 50 people at the conference. “We need to be able to manage this massive amount of information, especially as we increase the throughput.”
Speed is key because the number of chemical compounds that drug companies test against a particular enzyme has increased dramatically, from about 10,000 to 20,000 since the 1980s to about 1 million today, according to Keith Wood, Ph.D., research fellow with Promega Corp. in Madison, who spoke at the conference.
While research equipment companies are trying to find ways to increase the number of samples per test plate, thereby increasing speed, screening all those compounds against just one enzyme to find potentially useful ones still can take three months to a year, which may be one reason why only eight new molecular entities were approved by the FDA in 2002.
To quicken the hunt, Wood is working on developing photon-emitting probes that enable observation of a single target molecule, particularly fluorescent and chemically luminescent materials—all because scientists simply aren’t smart enough to predict how someone will react to a certain chemical, he noted. Therefore, “we’re trying to find a way to go through a large number of compounds to find out what would happen in the human body,” Wood said.
Another reason for the slowness of the process may be that pharmaceutical companies’ aversion to risk, i.e. accepting new discovery methods, said conference attendee Gerald Mattys, CEO of Medisyn Technologies, Wayzata , Minn.
Rather than follow the traditional path of singling out certain compounds that are active with a target enzyme or protein, Mattys and his team began by identifying a target disease, lung cancer, and then designing new molecules from compounds known to be active against lung cancer. That paradigm overhaul is not necessarily what drug companies want to hear, however.
“We’re finding in talking with pharmaceutical companies that they’d love to get their hands on new drugs; but you have to prove things the way they’re used to seeing them,” Mattys said. “The data that comes from old method is still required for you to get into door, rather than them taking risk and pulling a compound in early and doing an assessment without all data used to looking at.”
A third possible reason for the 18-year cycle: may be that researchers traditionally test compounds in a way that yields one set of results in a solution (in vitro) and quite another in a living organism (in vivo). That observation has led many researchers to gravitate toward cellular assays that test compounds in a manner that more accurately predicts what will happen in the body when it comes to absorption, distribution, metabolism, excretion and toxicity (adme-tox in laboratory parlance).
“I think that we will focus more on cell-based assays for the future,” said Millis, who received her Ph.D. in biochemistry from UW-Madison. “It will first of all hopefully decrease the time from drug identification to a new molecular entity on the market, and it will also increase the probability that the identified compound will actually act as a drug in vivo.”
Mattys noted that getting the industry to move on new and faster ways of doing drug discovery may get a jolt from the $35 billion worth of patented drugs due to lose their patents in the next three years.
“Certainly the senior executives see the need for riskier bets or new ways of doing business,” Mattys said. “But it’s not translating to masses yet in R&D organizations.”
New discovery platforms, such as ACTIVTox® from Amphioxus Cell Technologies in Houston, can more closely mimic the human body’s function. Amphioxus’ platform is a human liver cell line that faithfully reproduces normal processes in the liver, where most drugs are metabolized. Pierce and Amphioxus have a co-marketing agreement for ACTIVTox and a complementary Pierce technology.
As cell-based assays begin to gain a greater profile in the research community, the whole goal will be to give drug companies the means to reverse the falling tide of new drug approvals.
“If we wisely take the information we’re getting and apply it to screening for potential drugs, we’ll be able to decrease the time frame and increase correct drug potential,” Millis said.