Materials and Links

Background:

CCR5 antagonists, the next therapeutic class for treatment of HIV infection, have the potential to significantly alter the landscape of HIV treatment by providing a new class of drug that targets a host cellular receptor rather than a viral enzyme.

The development of any new drug class for HIV treatment occurs in the context of existing therapies and raises issues and concerns related to potential class-specific toxicities, drug resistance and pharmacokinetic interactions. The development of CCR5 antagonists raises additional issues specific to this class of drugs, including their effect on the dynamics of R5, X4 and R5X4 virus strains and the long-term effects on host inflammatory and immune systems.

Many of the issues that need to be addressed will be common to all CCR5 antagonists in development. A project designed to facilitate discussion on common issues has the potential of moving this field forward by providing clarity and reducing uncertainty and helping to achieve the development goals more rapidly compared to each organization working on their own. Such a "working group" would include representatives from regulatory agencies, pharmaceuticaland diagnostic companies, basic and clinical science, and advocacy.

The Forum for Collaborative HIV Research, a coalition of representatives from government, industry, patient advocates, health care providers, academia and foundations is ideally suited to host these discussions. The mission and goals of this project are a very good fit with the mission/goals of the Forum and our membership includes all of the entities listed. The Forum is a public/private partnership whose mission is to enhance and facilitate HIV research. This is accomplished by bringing together all relevant stakeholders to address emerging issues in HIV/AIDS. Through our work, we identify gaps and impediments, frame issues and help set research strategy. Regulators value the input they receive from Forum members outside the constraints of formal advisory committee meetings, and companies appreciate the ability to communicate with regulators on broad topics, rather than just within the narrow context of their own submissions. The goal is to optimize care and treatment of those affected by HIV/AIDS.

Objectives:

To help drive and advance the development of CCR5 inhibitors for the treatment of HIV infection by providing a neutral, all-stakeholder platform for ongoing discussions of issues.

• To develop consensus on development issues, such as appropriate monitoring of safety and efficacy in a range of diverse populations and other development issues
• To facilitate the flow of information and develop clarity on the various issues associated with the development of this drug class.
• To publicize the outcome of the discussions in the form of Forum reports, editorial reviews, presentations at major conferences

Topics to be addressed by the group include:

• Issues related to clinical research with CCR5 inhibitors in naïve patients
• Issues related to clinical research with CCR5 inhibitors in pre-treated patients
• Issues related to research in pediatric populations
• Diagnostic issues for identifying R5 and X4 tropic viruses
• Monitoring long-term effects on viral populations
• Monitoring long-term effects in host populations
• Impact of host CCR5 receptor gene heterogeneity on efficacy and toxicity

Status:

The first working group meeting was on May 23rd 2005 in Washington DC. A second meeting was held on December 14, 2005 in Washington DC.

The Steering Committee for this project includes:

Ben Cheng - Forum for Collaborative HIV Research
Lynda Dee - AIDS Action Baltimore
Bill Freimuth - Human Genome Sciences
Wayne Greaves - Schering-Plough
Trip Gulick - Cornell University
Dan Kuritzkes - Harvard University
Louise Martin-Carpenter- GlaxoSmithKline
Howard Mayer - Pfizer
Veronica Miller - Forum for Collaborative HIV Research
Jeff Murray - Food and Drug Administration
Neil Parkin - ViroLogic
Kim Struble - FDA