WASHINGTON - Executives from two companies whose biotechproducts passed muster last week before the FDA's Oncologic DrugsAdvisory Committee (ODAC) boiled down their advice to othercompanies seeking to learn from their success: Communicate wellwith the FDA and have good data.

In interviews with those executives, BioWorld Today asked them toelaborate on what seems to be awfully simple advice.

Last week the ODAC approved NeXstar Pharmaceutical Inc.'sDaunoXome, a liposomal formulation of the anticancer agentdaunorubicin. (See BioWorld Today, June 9, 1995, p. 1.) TheBoulder, Colo.-based company's Phase II data on DaunoXome hadbeen soundly rejected by ODAC two years ago.

However, the tone was much different this time around. ODACChairman Charles Schiffer, professor of medicine, University ofMaryland Cancer Center in Baltimore, praised NeXstar's Phase IIIrandomized clinical trial. He said that the next manufacturer seekingapproval for a similar therapy would have to address the fact thatNeXstar completed a randomized clinical trial.

U.S. BioScience, whose third application for Ethyol (amifostine), aselective cytoprotective agent, also was approved by ODAC lastweek said good communication was key to its success. (SeeBioWorld Today, June 12, 1995, p. 1.) The West Conshohocken,Pa.-based company had two previous applications for Ethyol rejectedby ODAC.

U.S. BioScience Senior Vice President Barbara Scheffler toldBioWorld Today that they listened when the FDA's medical officertold the company to focus its data on the issue of renal toxicity. AfterODAC rejected its second application for Ethyol, U.S. BioScienceofficials went home and reworked the data. "We performedadditional analyses to look at the renal toxicity issue in more detail,"Scheffler said.

Michael Ross, NeXstar's vice president for medical and regulatoryaffairs, attributed his company's failure to convince ODAC in 1993of the merits of DaunoXome to insufficient data. "We didn't have thedata. We went in with Phase II data - and limited amounts at that.Several members of ODAC told us that they knew DaunoXomeworked but that we didn't have the data to prove it.

"We should have waited longer until we had enough data beforeappearing before the advisory committee," Ross said.

Is Phase III data better than Phase II? Perhaps, Ross said. "By havinga randomized clinical trial, you know how your drug stacks upagainst another drug. You know its strengths and weaknesses," hesaid.

"Phase III data is easier to interpret and understand. Its main valuelies in the randomized data," Ross said.

"If you do go in with Phase II data, make sure you have discussed thedata with the agency. Make sure the data is carefully analyzed andyou recognize its limitations," Ross advised.

While U.S. BioScience was not plagued with data problems, it didhave a misconception at FDA to clear up. "After the second ODACmeeting on the Ethyol application, U.S. BioScience officialsdetermined that the FDA medical officer mistakenly thought thatrenal toxicity was only a secondary finding.

"But we pointed out that renal toxicity had always been a primaryend point. We thought that some of the confusion was a result of thenew FDA review team that had been in place for only a year and didnot know the history of the drug," Scheffler said.

"That misunderstanding underscored the need for U.S. BioScience tocommunicate more effectively with FDA," Scheffler said. It held aseries of meetings beginning soon after ODAC's second rejection.One even included ODAC Chair Schiffer. He was invited at therequest of FDA.

The meetings continued until right before last week's ODACmeeting.

"We built up a good rapport with the FDA medical officer andstatisticians. We responded to each of their requests for data and evenprovided them with full data sets so they could reproduce ourfindings," she said.

Scheffler urged other biotech firms to take a lesson from U.S.BioScience's mistakes. "When you are developing a product, youbecome so familiar with all of its aspects that every piece of dataseems clear."

"But we realized that you can't give an advisory panel 500 pages ofinformation. They won't get the message. Keep the presentationfocused and to the point. Look through the available data anddecided what's critical to your case," Scheffler advised.

Like U.S. BioScience, NeXstar devoted considerable time andresources to make sure the FDA understood its data and that thecompany appreciated the agency's concerns. "We worked hard atcommunicating with FDA. There have been multiple telephoneconversations each week since January. We provided the agency withall the data requested to perform their analysis," Ross said.

"FDA might have put a different spin on our data but there were noinappropriate criticisms," Ross said. n

-- Michele L. Robinson Washington Editor

(c) 1997 American Health Consultants. All rights reserved.