Washington Editor

WASHINGTON - ImClone Systems Inc.'s failure to advance its cancer drug Erbitux through the regulatory approval process may end up being the catalyst for change at the FDA.

After a six-month investigation into New York-based ImClone and its business practices surrounding development of Erbitux, the House Energy and Commerce Committee has called on the FDA to help examine the drug approval process to determine if such debacles can be avoided in the future.

The committee on Thursday issued a letter to Lester Crawford, FDA deputy commissioner, requesting a meeting with agency officials in order to sift through obstacles that would prevent it from implementing a Special Protocol Assessment approach to protocol development and clinical review within the Center for Biologics Evaluation and Research (CBER).

A Special Protocol Assessment is designed to evaluate individual protocols, primarily in response to specific questions posed by the sponsors.

The design of a well-controlled study agreed to by the drug company and agency in advance of a pivotal trial appears to be particularly important when the study employs surrogate endpoints and is done in a very small population, according to letter signed by committee chairman Billy Tauzin (R-La.) and James Greenwood (R-Pa.), chairman of the subcommittee on Oversight and Investigations. "Both these limitations characterized the studies at the heart of the expedited approval, fast-track submission by ImClone," the letter said.

Indeed, in its investigation, the committee said it found a series of problems associated with the rolling biologics license application (BLA) finalized in October. Aside from reported protocol violations in the clinical trials, ImClone failed to conduct a trial comparing Erbitux to Campostar, and the FDA admitted it used the wrong version of a Phase II trial to determine whether Erbitux would be fast-tracked. (See BioWorld Today, June 14, 2002; June 18, 2002; and Jan. 22, 2002.)

In its letter to Crawford, the committee said "the evidence presented in the hearing record supports the justification for FDA's action in refusing to file the BLA for Erbitux." However, the letter said, "the hearing also showed that the fast-track process in CBER needed improvement."

The committee said there should be a consistent approach to facilitating expedited review for cancer drugs and biologics. "Using Special Protocol Assessments for the design of the registration study or studies makes sense, yet has only been employed once by CBER," the letter said.

Funds have been provided under the Prescription Drug User Fee Act III for management review aimed at, among other goals, coordination of the review processes at CBER and CDER, the letter said. "It would appear that instituting common "best practices" procedures for drugs slated for accelerated approval, at least in the arena of protocols for clinical studies and evaluation of the clinical data flowing from there, for cancer drugs and perhaps other vital medications could and should be done without extensive study or delay."