Uncovering drugs that successfully combat neurodegenerative diseases such as Alzheimer's has been like finding a needle in a hayloft.
Industry statistics show that only 7 percent of experimental drugs to treat neurodegenerative disorders, which also include Parkinson's and Lou Gehrig's disease, make it through human trials to win regulatory approval. And these are drugs that already have survived animal testing and other screening measures because of their likely positive effect on certain diseases.
"There's a lot of room for improvement," said Brian Corrigan, a senior director at Pfizer Inc. in Groton.
So Pfizer, like several other major pharmaceutical companies, has turned to computer simulators to help boost the odds that they will design drug trials to bring much-needed treatments to patients as quickly as possible. Scientists at Pfizer's Groton labs have used predictive modeling for the past five or six years, and computer-simulation tools for at least three years, Corrigan said, and the company is employing them to help with four separate Alzheimer's drug-development programs.
While many drug failures over the years are related to lack of effectiveness or safety concerns, some are tied to inexact experimental designs that result in potential blockbuster medications being rejected because doses, trial durations or patient numbers are not optimal to yield statistically significant results. With simulators, Corrigan said, data from previous drug trials are used to play out various scenarios hundreds or thousands of times to help determine an experimental design that will most likely offer significant results.
Even using powerful computers in a cloud environment, "It takes days and days," Corrigan said.
These predictive tools reached a new era of acceptance in June when an Alzheimer's drug-trial simulator developed by the Arizona-based nonprofit Critical Path Institute won endorsement for the first time from the U.S. Food and Drug Administration as a so-called "fit-for-purpose" drug development tool. Janet Woodcock, director of the Center for Drug Evaluation and Research, said at the time that simulation "set the stage for applying new technologies to accelerating medical product development."
Other simulators are currently in the works to tackle tuberculosis, Huntington's disease and Parkinson's, according to a November article in The Wall Street Journal.
Helping clear the way for predictive innovations in drug research, companies such as Pfizer and Eli Lilly & Co. provided data from previous Alzheimer's drug trials to the Critical Path Institute, which partnered with the Coalition Against Major Diseases to reach out to the pharmaceutical industry, patient-advocacy groups, academic institutions and government agencies to help bring the project together.
"Alzheimer's disease clinical development tools that are derived from real-world findings and take into account a variety of factors help to increase our confidence that a clinical study is accurately designed," said Richard Mohs, a Lilly vice president, in a statement.
Richard Lalonde, head of clinical pharmacology at Pfizer, said major pharmaceutical companies shared data for more than 6,000 patients with mild to moderate Alzheimer's symptoms to help develop an effective simulation tool.
"This is a great example of a rising tide lifting all boats," he said in a statement.
Corrigan added that sharing information in a "pre-competitive space" allows all the participating companies to improve their understanding of the disease. It also meant developing a standardized scoring system that could be used to assess the effect of a given remedy on brain function, making it easier to compare results of drugs produced by different companies.
The idea is to develop simulation technology to the point that many of the spectacular drug failures seen in the industry over the past few years - including Pfizer's own heart medicine torcetrapib and Alzheimer's pill Dimebon - will be eliminated. Avoiding failures can save companies hundreds of thousands or even millions of dollars in drug-development costs that can easily surpass $1 billion for a major advancement.
Corrigan said simulators can be used at any stage of the drug-development process but are most likely to be employed at the end of midstage trials that show a medicine is safe and indicate a likelihood of effectiveness. This is when the complicated late-stage trials are conducted by trying medicines at various doses in a large number of patients.
It's not yet clear how successful simulators will be in improving the rate at which experimental drugs win approval, but Corrigan said he was confident that it is an important platform for analyzing information so that the industry can begin moving the needle on its current 11 percent chance of gaining approvals for all drugs that enter human testing.
"It's gaining a lot of traction," Corrigan said. "It helps us see if the trial design is appropriate for the treatment effect."