Washington Report: Opportunity Knocks

The Ides of March was eventful this year at FDA. The White House nominated acting commissioner Andrew von Eschenbach to take over the top job permanently. Then Health and Human Services (HHS) secretary Mike Leavitt joined him and deputy commissioner Janet Woodcock in unveiling a long-awaited list of "scientific projects" to accelerate the development of new medical products. Although Woodcock has been the prime force behind Critical Path, von Eschenbach gets credit for keeping it on the table. But his good efforts may not overcome the political issues blocking his confirmation (see "Nomination on Hold").

Jill Wechsler

Encouraging Collaboration

FDA launched Critical Path two years ago to reverse a downward trend in new drug approval (see "What Ever Happened to Critical Path," Pharmaceutical Executive, January 2006). The initiative aims to identify new research practices and biomarkers in order to streamline clinical studies and better ensure the safety and efficacy of new treatments.

Nomination on Hold

"We now have the science and technology to support a powerful engine for drug development," says James Shannon, head of pharmaceutical development at Novartis, "but the science has not been allowed to flourish in the current regulatory environment; the rules of the road say we can't drive more than 30 miles per hour."

FDA intends for many individual components of Critical Path to be carried out by consortia. One early model is the Predictive Safety Testing Consortium, established by the non-profit Critical Path Institute (C-Path) and eight pharma companies. The participants have agreed to cross-test each other's pre-clinical laboratory methods to determine which are most effective in detecting kidney, muscle, and liver toxicity.

C-Path will submit the resulting data to FDA, which will weigh whether the information supports new guidance on detecting kidney or liver safety problems during development. The goal is to identify the most informative tests—animal, in vitro, or clinical—for predicting toxicity, explains C-Path president Ray Woosley.

With early insight into which compounds have unacceptable side effects, companies can avoid spending on unpromising drug candidates and spur efforts to find safer compounds. Consortium members will have access to data on test methods—and opportunities to license resulting patentable technologies.

Informing Treatment

Another consortium, the Oncology Biomarker Qualification Initiative, was formed by FDA, the National Cancer Institute (NCI), and the Centers for Medicare and Medicaid Services (CMS). The group's first project is to evaluate whether PET scans can provide a marker for early drug response in non-Hodgkin's lymphoma. The project could create a new tool for assessing how well molecular imaging technology reveals drug interaction with a target. The results may be useful, moreover, for tumor staging and helping providers, payers, and patients make treatment and coverage decisions.

Woodcock regards the opportunities list as an evolving document and expects to issue an update of activities underway this summer. One project on the table is an FDA–industry effort to identify biomarkers that already exist, to demonstrate the practical value of such measures.

FDA participated in an Institute of Medicine workshop on cancer biomarker development in March and plans to hold a workshop on what type of evidence is needed to qualify biomarkers for different purposes. This should lead to a general biomarker qualification guidance describing ways to link biomarker validation to intended uses. Additional guidances on specific qualified markers will follow, possibly starting with documents on testing for liver and kidney toxicity. Also on the agenda is draft guidance on drug–diagnostic co-development.

These joint efforts call for drug companies to share data on test results and best practices, something industry is generally reluctant to do. To create the C-Path safety consortium, dozens of lawyers had to define a pre-competitive area for collaboration that avoids anti-trust violations. Participants believe it is in everyone's interest to identify better markers for drug safety and disease, says Shannon. But such projects could collapse if participants don't pull their weight or wrangle over intellectual property. And Critical Path could lose its impetus under less supportive FDA leadership.

Patches and Inhalers

Another opportunity for collaboration involves developing innovative approaches for testing and producing novel drug dosage forms. The Critical Path calls for new testing instruments for delivery systems, such as patches, liposomes, topicals, and nasal and pulmonary inhalers.

Interest is especially keen in this area, since FDA has recently approved several new delivery products, including the first inhaled insulin, Pfizer's Exubera, and a patch treatment for major depression, Somerset's Emsam (selegiline). A patch for ADHD was approved last month.

Such products are popular because health plans and patients appear willing to pay a premium for products they can administer at home with less discomfort and less risk of safety problems. Drugs may be absorbed better from inhalers and patches, which means that patients can take smaller doses—which are less likely to create undesirable side effects.

However, recent evidence that heat effects may overly increase drug absorption rates from patches is prompting a closer look at new dosage forms. FDA's Office of Testing and Research is studying ways to ensure the quality and safety of patches and inhaled drugs; it is studying patch adhesion to skin, in vitro test methods to assess drug release from patches more efficiently, and how to set standards for evaluating factors affecting the quality of inhalation drugs.

Encouraging Generics

Such analysis is likely to facilitate the approval of generic versions of innovative dosage forms. FDA recently approved the first generic allergy nasal spray from Boehringer Ingelheim's Roxane Labs, a version of GlaxoSmithKline's Flonase (fluticasone propionate). Reviewing this first generic nasal spray-suspension product was a challenge for FDA's Office of Generic Drugs, and points to the need for additional standards for new delivery systems. In a speech to the Generic Pharmaceutical Association in February, FDA deputy commissioner Scott Gottlieb pointed out that most topical creams are difficult to evaluate for efficacy with standard in vitro analysis and bioequivalence testing. And liposomes, which can target a therapy to selected tissues, require new methods for assessing bioequivalence.

Resolution of scientific and technical issues related to generic drug bioequivalence is likely to remove some roadblocks to marketing innovative generic products. GSK raised legal and scientific objections to generic Flonase, but gave up after a negative federal court ruling. Meanwhile, Glaxo had hedged its bets by licensing Par Pharmaceuticals to market an authorized generic version, an increasingly common strategy for innovator firms seeking to retain some revenues from blockbuster products facing new generic competition.

The practice, though, has attracted attention from federal watchdogs. The Federal Trade Commission recently announced a broad study on prices and policies related to authorized generics, as requested last year by Senate Finance Committee chairman Chuck Grassley (R-IA) and two Democrats. In addition, the HHS Inspector General plans to assess the effect of authorized generics on Medicaid drug pricing and rebates. Congressional committees expect to hold hearings on the topic, with a focus on how authorized generics should relate to "best price" Medicaid calculations.

The FTC seeks to subpoena wholesale price data, including rebates and discounts, for brand-name and generic drugs from almost 200 pharmaceutical manufacturers. The agency will examine licensing agreements and business plans to assess how authorized generics affect market entry and prescription drug prices. Pharma has until June to comment on whether the FTC is overburdening industry by asking so many companies to produce so much information.

Jill Wechsler is Pharm Exec's Washington correspondent. She can be reached at jwechsler@advanstar.com