Regulatory Focus™ > News Articles > HIV Drug Development Guidance Revised, Reflecting New Approach to Treatment-Resistant Populations

HIV Drug Development Guidance Revised, Reflecting New Approach to Treatment-Resistant Populations

Posted 04 June 2013 | By Alexander Gaffney, RAC

US regulators have released a new guidance document aimed at providing clarity to the process of developing drug products to treat-not prevent the transmission of-Human Immunodeficiency Virus-1 (HIV-1), bringing up to date a development paradigm last updated more than a decade ago.

The guidance revises Antiretroviral Drugs Using Plasma HIV RNA Measurements--Clinical Considerations for Accelerated and Traditional Approval, a guidance released to the public in 2002.

FDA regulators said the guidance contains four major changes:

  • more details on nonclinical development
  • a greater emphasis on recommended trial designs for HIV-1-infected heavily treatment-experienced patients for whom there are few remaining treatment options
  • use of a primary endpoint evaluating early virologic changes for studies in heavily treatment-experienced patients
  • use of the traditional approval pathway for initial approval of all antiretrovirals with primary analysis time points dependent on the indication sought instead of an accelerated approval pathway followed by traditional approval

"Longer term trials may be appropriate for patients who are treatment-naïve or have limited prior experience, whereas shorter term trials may be appropriate for patients with limited treatment options," FDA explained.

The guidance goes on to recommend that studies designed to meet the needs of treatment-experienced patients, those patients for whom few existing therapies may still work, use a factorial design using several products at once if multiple drugs are available for use, and a placebo-controlled superiority trial if only one option is. Such trials should be short, as longer term comparisons run the risk of the virus developing resistance to the investigational treatment.

Instead, FDA recommends a primary efficacy evaluation of an investigational drug versus a placebo occur at 7-14 days after initial treatment. Thereafter all patients can receive the investigational new drug, followed by a second assessment at 24 weeks to assess for response, safety, durability of response and viral resistance.

The entire 43-page guidance may be found here.


Draft Guidance: Human Immunodeficiency Virus-1 Infection; Developing Antiretroviral Drugs for Treatment

Federal Register


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