Lenacapavir Demonstrates Small Margin of Resistance for Those Heavily Treated With HIV

A minority of patients with HIV administered lenacapavir (Sunlenca; Gilead Sciences Inc) demonstrated resistance to treatment and patients with inadequate adherence to their optimized background regimen (OBR) or without fully active antiretrovirals as part of their OBR for treatment of multi-drug resistance and an extensive treatment history, according to new data from the phase 2/3 CAPELLA trial (NCT04150068).

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Lenacapavir is a long-acting injectable for HIV that is administered twice yearly. The new data from the study were presented at the 19th European AIDS Conference in Warsaw, Poland, from October 18 to October 21, 2023.

“The bar is rightly now set high for the efficacy and safety of HIV treatment across a diverse range of [individuals] living with the virus. The next wave of innovation in HIV includes long-acting options that are aiming to help address the differentiated needs and preferences of the diverse range of individuals and communities affected by the epidemic,” Jared Baeten, MD, PhD, vice president of HIV Clinical Development at Gilead Sciences, said in a statement. “These unmet needs fueled our research teams at Gilead to develop [lenacapavir], an innovative treatment option that helps respond to the unmet needs of adults with limited therapy choices.”

The phase 2/3 study was designed to evaluate the safety and efficacy of the drug in combination with other antiretrovirals as part of an OBR. There were 72 individuals enrolled in the study with advanced HIV.

Of the 27 individuals who met resistance criteria, investigators reported that 13 did not develop resistance to lenacapavir whereas 14 developed lenacapavir resistance-associated mutations. The 14 individuals were found to have inadequate adherence to the OBR or an OBR lacking fully active antiretrovirals.

Of the 14 patients, 7 who were resistant to lenacapavir also repressed during re-adherence to OBR or with a change in OBR. Investigators said the findings emphasize the importance of more than 1 fully active agent, when possible, for a regimen for those with multi-drug resistant HIV and limited therapy options.

Furthermore, in a survey that included 25 health care professionals in the CAPELLA study and study coordinators, the majority said lenacapavir would be easy to integrate in real-world clinical practices. They also reported that lenacapavir has a strong potential to improve clinical outcomes and health-related quality of life for those who are heavily treatment-experienced, according to the statement. All individuals in the survey also reported that the injection site reactions did not alter the patients’ willingness to continue treatment.

Lenacapavir is approved in Australia, Canada, the European Union, Israel, Japan, Switzerland, the United Arab Emirates, the United Kingdom, and the United States for individuals with multi-resistant HIV in combination with other antiretrovirals, according to the statement.

Gilead Sciences is currently working to offer long-acting oral and injectable options of lenacapavir as a single agent for prevention of HIV, aiming to address the needs of patients with HIV and those who would benefit from pre-exposure prophylaxis. The use of lenacapavir for HIV prevention is currently investigational and the safety and efficacy has not been established for this use. It is being evaluated as a long-acting treatment option in multiple ongoing and both planned early- and late-stage clinical trials.

References

New data presented at EACS 2023 further demonstrate strong clinical profile of twice-yearly Sunlenca for adults with multi-drug resistant HIV. News release. Gilead Sciences. October 20, 2023. Accessed October 24, 2023. https://www.gilead.com/news-and-press/press-room/press-releases/2023/10/new-data-presented-at-eacs-2023-further-demonstrate-strong-clinical-profile-of-twice-yearly-sunlenca-for-adults-with-multi-drug-resistant-hiv