BioWorld International Correspondent

BRUSSELS, Belgium - The European Medicines Agency said the carcinogenic risk posed by HIV medicines needs to be reconsidered, and it outlined Monday its concept for new guidance on genotoxicity and carcinogenicity evaluation of those agents.

The agency is concerned because some classes of anti-retroviral agents have shown equivocal genotoxic properties, others are clearly genotoxic and nearly all have exhibited positive findings in the available two-year rodent carcinogenicity studies.

As the agency pointed out, when those agents were introduced, the life expectancy of HIV patients was limited and any potential carcinogenic hazard was of low relevance. But because the outlook for HIV-infected patients on medication has increased in recent years, "a carcinogenic risk should be considered now in the evaluation of the benefit/risk balance of these products."

So far, HIV products usually have been exempted from the standard carcinogenicity studies required before a new medicine is authorized. The agency is proposing that the exception might be limited in the future only to substances with a clear additional clinical benefit to the currently available therapy, based on a case-by-case assessment.

Potential carcinogenicity also should be addressed prior to long-term exposure in pediatric clinical trials, the agency said, and there also is a need to study the hazard of an interaction from the reported additive mutagenic effects between nucleoside reverse transcriptase inhibitors.

The agency's safety working party and its experts on HIV medicinal products are expected to draft a guideline for the pharmaceutical industry, for release for consultation in May. The aim is a more consistent assessment of applications for marketing authorization by regulators.

Separately, but also on Nov. 22, the agency released plans for new guidance to industry on nonclinical testing for inadvertent germline transmission of gene-transfer vectors. It is concerned about vertical germline transmission of vector DNA from exposure of gonadal tissue to gene-transfer medicines.

While inadvertent germline transmission has not been observed in clinical trials to date, there have been recent findings of vector DNA in semen of clinical trial participants. With new technologies allowing more advanced and effective in vivo gene-therapy strategies, the risk of inadvertent germline transmission might increase; updated guidance on the extent of nonclinical testing to investigate the risk is warranted, the agency said. The new guidance also is expected to be released for consultation in May.