NeoPharm/FDA IL-13 Soon To Enter Clinic; Elengold Details CBER Research

FDA's first major research collaboration with regulated industry will enter Phase I clinical trials in the near future, FDA's Center for Biologics Evaluation & Research Deputy Director for Operations Mark Elengold told the PDA/FDA joint conference Sept. 29.

In October 1997, FDA struck a cooperative research and development agreement with NeoPharm whereby the Bannockburn, Ill. company will commercialize an interleukin-13 anticancer immune therapy that was discovered in CBER labs.

Elengold described IL-13 PE38QQR as a Pseudomonas exotoxin anticancer agent that was discovered in the lab of CBER researcher Raj Puri, MD/PhD. The discovery was made "by Dr. Puri and his group in developing various methods for dealing with an application potentially for IL-13," he said.

"What he found was, it was possible to join the IL-13 molecules with various oncologic agents that would be targeted specifically to the tumor cell sites," Elengold explained. "Further studies are being investigated in vivo in animal models at this point, and we are expecting a Phase I clinical trial to begin real soon."

Elengold presented the collaboration as evidence that CBER research is an integral part of the center's function and can lead to novel therapeutics. FDA Commissioner Henney has continually emphasized building the FDA science base.

FDA research sometimes is conducted specific to a sponsor's product in review development or specific to a policy issue affecting the industry (such as defining a disease area). Often, research is associated with creating review standards and methods for review for modalities, such as xenotransplantation or gene therapy, Elengold said.

Over the past few years, CBER research has received a declining level of funding. Alternative funding arrangements, including partnerships, have been sought. Partnership mechanisms include Cooperative Research And Development Agreements (CRADAs), interagency agreement grants, and material transfer agreements, whereby reagents and supplies can be exchanged between collaborators while protecting intellectual property rights. CBER enters about 30 MTAs annually, Elengold reported.

Another CRADA supporting center research is with the Cystic Fibrosis Foundation for the development of hybrid nucleotide vectors as tools to repair defective CFTR genes. Correction of the CF gene contrasts with other research focusing on gene replacement.

FDA also has an agreement with NIH's National Institute of Allergy and Infectious Diseases to investigate regulation of chemokine anti-HIV activity by proteolytic processing. "We understand the protein process and pathways that control the immune therapeutic activities...When the license applications for those types of products hit our doorway, we...will not have to get up to speed."

CBER has a second collaboration with NIAID, for development of an edible recombinant DNA tuberculosis vaccine. CBER gives NIAID "BL3" laboratory space and NIH provides funding for CBER's research on edible TB vaccines. "That's the one you read about in the paper every couple of weeks, where they are going to put a gene into a carrot that is going to provide immunity," Elengold noted. "We are not the primary people pushing it but we are involved with those people who are, because ultimately we need the scientific expertise to review it."

An interagency agreement with the Department of Defense is investigating CPG-based oligonucleotides as rapid-induction vaccines against possible biowarfare agents. CBER has also begun a project with the World Health Organization.

Elengold noted that CBER does accept monetary and non-monetary gifts to the agency, but they may "not pose any real or apparent conflict of interest." He noted that some CBER investigators "have been able to fund their research with grants from various disease-based organizations. We also have built a funds-only CRADA, where there is no material, people, or equipment exchanged; it is only so we will be able to accept money," he explained.

While CBER develops its own research plan each year, "we receive a fair number of unsolicited proposals," Elengold said. "The procedure for approval is a very cumbersome one, designed to prevent real or apparent conflicts of interest. When we have a CRADA we write it up with the company." The offices of facilities and acquisitions, general counsel, ethics, and the CRADA review board have to approve it, and then the other center directors look at it. "We are working on streamlining that and down-delegating approval authorities to the center," he said.