"You don't need fancy math to tell you that pharmaceutical productivity is in trouble," said Mahdi Fawzi, keynote speaker at the Molecular Medicine Tri-Conference on February 22 in San Francisco, California. But you do need solid calculations if you want to reverse that trend.

The pharmaceutical industry spent a whopping $38 billion on drug development in 2005 but still came up short, with only 20 new FDA-approved drugs. The year before saw 36 such approvals.

Fawzi, executive vice president of preclinical development at Wyeth, shared some of his company's strategies for combating productivity problems, including some of the latest tweaks to the new system.

It's no secret that Wyeth has made major changes in how it does things, led by new R&D head Robert Ruffolo, who came on board in 2000. One fundamental switch was to "embrace attrition," as Fawzi explains. Once they accepted that 80% of all their compounds would fail at some point in development, they were able to estimate how many projects were needed at each stage to keep the pipeline fed. That meant increasing development-stage projects three-fold — going from 4 per year to 12. The company expanded every other stage of the pipeline as well, with a goal of submitting 2 new molecular entities (NMEs) to regulators each year.

Of course, no plan goes forward without some hitches. As they evaluated their progress, Wyeth's management was dismayed to learn that the true overall attrition rate was actually even higher than their original calculations. In reality, 85% of compounds were dropping out at some point. That meant they had to bump up the number of projects entering the beginning of the pipeline accordingly: 15 projects are now set in motion to reach the same goal of 2 NMEs per year. (See Table 1 below.)

"He [Ruffolo] has re-engineered the whole system, and the sustained results speak to his success," said Fawzi. Over the past 61 months, Wyeth has put 62 compounds into development. The time it takes for projects to go from the very first step in development to an investigational new drug (IND) submission has been cut from 23 months to 12. Most important, the company has filed more than 50 INDs over the past five years without having a single regulatory hold-up. None of its new drug applications have been held up either.

The changes at Wyeth are broad and bold. "We aligned our vision throughout the R&D function," Fawzi said. Preclinical development is now divided into learning and confirming phases. During the first of these phases, the focus is on clinical proof-of-concept and seeing in vivo correlation with in vitro studies. Instead of "wishful thinking, the work is data driven," Fawzi said. Projects do not advance until they are truly validated.

On the other side of that fence, in the confirmatory phase of development, the focus turns to maximizing success. Here, risk-taking is minimized and the goal is to have back-up plans at the ready in order to help projects meet aggressive timelines.

Other changes include such practical steps as having a single batch of drug available for both IND-enabling toxicology and first human studies. Scale is also being increased where needed. Fawzi said the company is "gearing up" to be able to do approximately 3,000 pharmacokinetic studies per year.

The Wyeth model does not rely heavily on outsourcing either. "If you reduce cycle time, you don't need to outsource," he said. Wyeth used to spend about $130 million per IND filed. That figure is now closer to $23 million.

As Fawzi admitted, the big question is, "Can we sustain it?" Or will additional adjustments, even major ones, be required down the line? For now, Wyeth has at least addressed one of the biggest problems in the industry by actually having a full pipeline to even worry about. 

Table 1: Wyeth's Preclinical Productivity Equation: Reaching 2 NMEs/Year

 Source: Adapted from Mahdi Fawzi presentation, Molecular Medicine Tri-Conference, February 22, 2006.

 ©  Copyright 2006, Cambridge Healthtech Institute. All Rights Reserved.