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The first final guidance in over 13 years for the development of new antiretroviral drugs for the human immunodeficiency virus (HIV) has been released by the US Food and Drug Administration (FDA).
The first final guidance in over 13 years for the development of new antiretroviral drugs for the human immunodeficiency virus (HIV) has been released by the US Food and Drug Administration (FDA).
The final guidance, titled Human Immunodeficiency Virus-1 Infection: Developing Antiretroviral Drugs for Treatment, replaces the draft guidance under the same name that was issued in June 2013. It also takes the place of the final guidance issued in October 2002, titled Antiretroviral Drugs Using Plasma HIV-RNA Measurements — Clinical Considerations for Accelerated and Traditional Approval.
The purpose of antiretroviral therapy is to suppress the viral load, called plasma HIV-ribonucleic acid (RNA) levels. The current way to go about this is typically with three antiretroviral drugs from two or more classes, and sometimes even more in certain patients. The new final guidance addresses the development of clinical trials to test novel antiretroviral drugs moving forward.
“For new HIV drug combinations of two or more or more early stage entities that are not expected to offer benefits over currently effective therapy, combination toxicology studies usually should precede phase II and phase III clinical trials evaluating the investigational combination as referenced in ICH M3(R2) [Nonclinical Safety Studies for the Conduct of Human Clinical Trials and Marketing Authorization for Pharmaceuticals],” the final guidance specifies.
The FDA stresses that the guidance does not address preventing HIV transmission with antiretroviral drugs. It also does not discuss how non-antiretroviral drugs should be developed.
The guidelines are broken down based on patient population:
The FDA recommends the following primary endpoints for phase II and phase III trials:
The secondary endpoints should focus on:
Time points for measuring viral RNA will vary depending on the patient population in the study, but early assessments (with one to four weeks) are particularly important in Group 2.
“Because treatment of HIV requires multiple drugs to achieve and maintain viral suppression below detection and to reduce the emergence of drug resistance to single drugs and drug classes, treatment INDs [investigational new drugs] that include two or more investigational drugs or that allow co-enrollment in several treatment IND programs simultaneously are desirable,” the guidance concludes.