Washington Editor

WASHINGTON - Firms seeking to gain approval of follow-on biologics (FOBs) should be required by law to conduct clinical trials to demonstrate the products' safety and effectiveness, the Pharmaceutical Research and Manufacturers of American (PhRMA) told a congressional subcommittee.

However, the lobbying group for the drug industry said, the FDA should be granted the authority to establish the type and extent of data necessary to support FOBs' approval applications.

PhRMA noted that FOBs trials might be less extensive or different from those used for approval of the referenced innovator products.

But the Generic Pharmaceutical Association argued that a statutory mandate for FOBs trials is unwarranted and that the FDA should be given the discretion to make decisions about such studies on a case-by-case basis.

Reps. Frank Pallone (D-N.J.), chairman of the House Energy and Commerce Subcommittee on Health, and ranking member Nathan Deal (R-Ga.) invited 36 groups in early April to respond to specific questions about their views and concerns on follow-on biologics to help the lawmakers determine a legislative path forward.

The subcommittee recently released the responses from 29 of those groups.

Lawmakers have introduced five pieces of FOBs legislation that seek to create a regulatory pathway for the FDA to approve such products in the U.S. The European Union established an approval path for FOBs, or biosimilars as they are known there, in 2004.

Jim Greenwood, CEO of the Biotechnology Industry Organization, said that while his group strongly supports the passage of an FOBs bill this year, he insisted that the legislation should recognize that biologics are fundamentally different from traditional medications in their complexity, development and production processes, and that FOBs "are not generic drugs."

Biologics are manufactured from living cells or organisms by programming a cell line to produce a desired protein in a highly controlled environment. The manufacturing process for each biologic largely defines the clinical properties of the resulting product.

Since an FOBs version will be manufactured using a different cell line and process from that of the innovator biologic, it will "inevitably lead to differences in the structures" between the two products, Amgen Inc. wrote in its response to questions posed by the subcommittee.

"As it is not possible to predict the clinical consequences of such differences, it is necessary to conduct clinical studies in order to demonstrate similarity to the innovator biologic and an absence of clinically meaningful difference," the Thousand Oaks, Calif.-based biotech contended.

Clinical trials always will be important to address questions such as immunogenicity, pharmacokinetics and common adverse events under controlled conditions before a product is marketed, Genentech Inc. maintained in its response.

"New legislation should not cause patients to take a biologic that had not been appropriately tested in humans; the risks are too high," the South San Francisco-based firm declared.

Genentech argued that there are many examples of how "seemingly minor changes in a biologic's manufacturing process have resulted in significant changes in the product - changes that could only be detected through clinical testing."

Millennium Pharmaceuticals Inc. said that at least some level of human trials should be mandated for all FOBs. However, the Cambridge, Mass.-based firm said the FDA should be given discretion about the scope of such trials, provided that the agency addresses those issues in product-class specific guidance.

"This will ensure that the American public is exposed only to FOBs that are demonstrated to be safe and effective, and not to result in adverse immune responses," Millennium stated.

But the public advocacy group Consumers Union, which publishes Consumer Reports, argued that clinical trials for FOBs "should be the exception and not the rule," and only be required in special circumstances at the discretion of the FDA.

"A requirement for clinical trials is too high a barrier for the FOB industry," the group contended, adding that a requirement for clinical trials would inhibit the development of FOBs and would be costly to the industry.

The more the legislation allows FOBs to be regulated like generic drugs - while letting science drive the decisions at the FDA - the greater the savings and access to consumers will be realized, said Seattle-based Cell Therapeutics Inc.

The company suggested that legislation that creates a pathway for regulatory approval of FOBs should be similar to the 1984 generic drug law or the FDA's 505(b)(2) guidelines, to ensure that the FDA does not take an "unreasonable position" that could negate lawmakers' intent.

The Federal Trade Commission cautioned lawmakers to avoid some of the pitfalls and unintended consequences that plagued the 1984 generic drug law, specifically, loopholes that have allowed exclusion payment settlements, which have forestalled entry of cheaper generic versions of drugs into the marketplace.

Such agreements are settlements of patent litigation in which the brand-name drug firm pays its potential generic competitor to abandon the patent challenge and delay its product's entrance into the market.

Exclusion payment settlements are becoming more prevalent, the FTC said. At least 33 such settlements were finalized in 2007, according to the agency. (See BioWorld Today, May 27, 2008.)

"In any legislation on generic biologics, Congress should seek to avoid creating a new arena for this costly type of collusion," FTC Acting Secretary Landis Plummer told the subcommittee in the agency's response.

FDA Calls for Black Box on Older Antipsychotics

The FDA last week used its new powers granted by Congress to require makers of older, so-called conventional antipsychotics to add a black-box warning in product labeling.

The agency previously had to negotiate such changes with drugmakers, but under the FDA Amendments Act of 2007, regulators now can demand, rather than request, safety labeling changes.

The new warning alerts prescribers about an increased risk of death in elderly patients treated with antipsychotics for dementia-related psychosis, an unapproved indication.

A similar boxed warning was added in 2005 to the labeling of atypical antipsychotics, which are newer drugs.

Antipsychotics are approved primarily to treat symptoms associated with schizophrenia. However, regulators noted, physicians are increasingly prescribing the drugs for off-label uses, such as dementia-related psychosis.

Some of the drugs that will receive the new boxed warning include Haldol (haloperidol), Loxitane (loxapine), Compazine (prochlorperazine), Stelazine (trifluoperazine) and Thorazine (chlorpromazine).

However, during a briefing with reporters, regulators acknowledged that it was unclear how many of the older antipsychotics remained on the U.S. market and which firms still are marketing the drugs, which are available mainly in generic forms.

GSK Shares Cancer Cell Lines with Public

Pharma giant GlaxoSmithKline plc has made genomic profiling data for more than 300 cancer cell lines publicly available to the National Cancer Institute's Bioinformatics Grid (caBIG).

The NCI's caBIG network, launched in 2004, enables the collection, analysis and sharing of data and knowledge from laboratory bench to patient bedside.

Access to the data, which is available free on the NCI's website, allows researchers at academic institutions, small research facilities and nonprofit organizations to forego the costs and time involved in identifying and cataloging each cell line.

The genomic data being shared by London-based GSK through caBIG come from cell lines derived from a wide variety of tumors, including breast, prostate, lung and ovarian cancers, the firm said.

"The ability for researchers to share data via the caBIG network is exactly what this initiative was designed to enable," noted Robert Clarke, professor of oncology, physiology and biophysics at Georgetown University in Washington.

"As more scientists throughout the cancer community, in the U.S. and globally use caBIG and find it easy to share data and collaborate, both basic and clinical research will be improved," he added.