The US Food and Drug Administration (FDA) on Wednesday issued a new draft guidance detailing its expectations for sponsors looking to develop systemic drugs for pre-exposure prophylaxis (PrEP) to prevent sexually acquired HIV-1 infection.
FDA says the guidance covers the overall development program and clinical trial designs for developing such drugs, which can include new investigational drugs (INDs) or already-approved HIV drugs that are repurposed or reformulated for PrEP use.
For sponsors looking to develop investigational drugs, FDA says it encourages early communication via the pre-IND new drug application consultation program
In the draft guidance, FDA provides considerations for the nonclinical and clinical development of HIV PrEP drugs, as well as recommendations for dose selection, patient adherence and clinical trial design as well as special considerations for pregnant women and adolescents.
For nonclinical development, FDA refers sponsors to its guidance Human Immunodeficiency Virus-1 Infection: Developing Antiretroviral Drugs for Treatment
for virology considerations.
FDA says sponsors should evaluate whether the drug under investigation has the potential to enhance HIV infectivity.
"For example, sponsors should evaluate monoclonal antibodies for potential antibody-dependent enhancement of infection," FDA writes.
The agency also says that animal models of infection can be used to support clinical development, such as identifying potentially effective drug combinations or dosing regimens.
For pivotal studies, FDA says sponsors should conduct two adequate and well-controlled phase 3 studies in healthy, non-HIV-infected sexually active adult men and women who are at risk of acquiring HIV.
However, FDA says that a single phase 3 study may be acceptable if the results of the study are "statistically persuasive" and supported by additional evidence, such as having previously been demonstrated to be effective at treating HIV. Sponsors considering a single phase 3 trial are instructed to contact FDA's Division of Antiviral Products to discuss their approach beforehand.
FDA also recommends that sponsors use HIV infection rate per 100 person-years as the primary endpoint for their studies, and that all participants in the trial be followed for at least a year, with the majority of participants receiving 24 months of follow-up.