By Karen Pihl-Carey

BOSTON - If every biotech company got its wish, all drugs with good data would fly through the regulatory process and land on the market in a matter of days and weeks instead of months and years.

But while some products - those on a fast-track status or with an orphan drug designation - may receive accelerated approval, that is not the case for most, leading many biotech officials to the conclusion that they must seize these opportunities when they can.

Such was the subject of a panel discussion Tuesday at the BIO 2000 conference. By the second full day of the Biotechnology Industry Organization's seventh annual conference, 10,000 people had registered - twice the number registered at the 1998 conference in New York.

At the session titled "Accelerated Approval: Challenges and Rewards," panelists highlighted the criteria used in bringing a product quickly to market, using Centocor Inc.'s Remicade as a prime example. And a survey, conducted by the University of California at San Diego (UCSD) and PricewaterhouseCoopers, suggests the relationship between the FDA and the biopharmaceutical industry is improving in many areas, allowing important drugs to be quickly expedited through the regulatory process.

With two trials showing Remicade (infliximab) efficacious in patients with Crohn's disease (CD), Malvern, Pa.-based Centocor was able to gain accelerated approval from the FDA in August 1998 for the moderate-to-severe cases of the disease. The FDA required the company to conduct two additional Phase IV studies to determine optimal therapeutic maintenance regimens for patients with moderate-to-severe CD and fistulizing CD. (See BioWorld Today, Aug. 25, 1998, p. 1.)

The added trials are worth the accelerated approval in what Thomas Schaible called a "win-win" situation all-around, for the company, the FDA and the patient population.

"It got us to market quickly," said Schaible, senior director of immunology medical affairs at Centocor. "This is definitely a therapy that meets an unmet clinical need."

But traveling the road to accelerated approval requires surrogate endpoints and data that often are hard to find in small patient populations. Gathering clinical outcome data may take years, said Alison Lawton, senior vice president of regulatory affairs at Genzyme Corp., of Cambridge, Mass.

Nevertheless, unproven surrogate endpoints "need to be shown that they're reasonably likely to predict clinical benefit," Lawton said.

Having an orphan drug designation, meaning less than 200,000 patients suffer from the disease indication, often helps in gaining accelerated approval of a product. Yet companies may find it difficult to enroll the number of patients needed in studies to show statistical significance, Lawton said. Another problem is enrolling patients in the randomized, placebo-controlled Phase IV trials, often required by the FDA for accelerated approval.

"It raises some interesting ethical questions," Lawton said.

If there are no other existing therapies and the drug is available on the market, it is difficult to justify placing patients on placebo when they have no other therapy to the product being studied.

Mark Walton, of the FDA's division of clinical trial design and analysis, said measures, such as the surrogate endpoints and Phase IV trials, must be in place to deal with safety concerns and to weed out unworthy products.

"The accelerated approval is not intended to enable marketing of a product with inadequate confidence that it provides an effect," he said.

Specifically, Walton said, accelerated approval is for a products studied for safety and effectiveness in treating serious or life-threatening illnesses, with the studies showing the product provides a meaningful benefit over existing therapies. Serious means an aspect of the disease has an important impact on the patient's day-to-day function, he said.

The survey conducted by UCSD and PricewaterhouseCoopers found that 48 percent of respondents categorized their communications with the FDA as "excellent," as compared to 41 percent in 1997 and 34 percent in 1995. It also found that 64 percent of respondents indicated the FDA returned inquiries within five days, as compared to 52 percent in 1997 and 45 percent in 1995.

There is a down side, however. Respondents said inadequate technical expertise by the FDA reviewers, as well as a high turnover rate among reviewers, contributed to a delay in approvals.

But sometimes a delay is caused by lack of a company's clarity in its submission to the FDA, said Donald Grimm, managing director of the Improving America's Health survey and former CEO of Hybritech Inc., of San Diego.

"This is always a two-way street," he said. "We have some work to do on our side of the fence on this issue."