Long-Acting Lenacapavir Shows Efficacy in Heavily Treatment-Experienced Patients
Findings from the CAPELLA study reveal virologic suppression and a safety profile for multidrug-resistant HIV-1.
Onyema Ogbuagu, MD
Image credit: IDWeek 2024
A recent study presented at IDWeek by Onyema Ogbuagu, MD, associate professor of medicine and pharmacology at Yale School of Medicine, highlights the efficacy of long-acting subcutaneous lenacapavir (LEN) for treating multidrug-resistant HIV-1 in heavily treatment-experienced (HTE) individuals. Over a three-year period, the CAPELLA study demonstrated significant virologic suppression and a favorable safety profile for this first-in-class capsid inhibitor.
Study Details
At the conclusion of the CAPELLA study, 61% of participants achieved HIV-1 RNA levels below 50 copies/mL. This figure increased to 84% when excluding individuals with missing data. Notably, 88% of those receiving LEN achieved a half-log reduction in viral load, compared to only 17% on placebo.
In our exclusive interview with Ogbuagu, he stated, “We're excited to present the three-year results from the CAPELLA study, which looked at lenacapavir. This is an exciting compound because it's a first-in-class novel capsid inhibitor for HIV treatment, studying it in patients for whom there is an identified need.” He emphasized the unique position of this therapy in addressing the complex challenges faced by HTE patients, who have often exhausted available treatment options.
The study enrolled 72 participants, with a median age of 52 years. Among them, 64% had a CD4 cell count below 200 cells/μL. By Week 156, the median increase in CD4 cell count was 115 cells/μL, indicating improved immune function among participants. Ogbuagu remarked on the significance of these findings: “These are really amazing numbers for a very hard-to-treat population. Our study showed that even as far out as three years, the injection was safe and well tolerated.” Participants received LEN oral initiation followed by subcutaneous (SC) LEN every 6 months combined with an OBR.
In terms of safety, injection site reactions (ISRs) were primarily mild, with most reactions categorized as Grade 1 or 2. Dr. Ogbuagu underscored the importance of thoroughly assessing the safety profile of LEN, saying, “One of the new categories of adverse events we consider with parenterally administered compounds like lenacapavir is injection site reactions, which we don't worry about with oral therapies.” He noted that while ISRs were common, the vast majority of cases were manageable and typically resolved quickly.
“The good news is that, in general, even though the vast majority of participants did have some form of injection site reactions, they tended to be mild—typically Grade 1, with occasional Grade 2 reactions,” he explained. He also acknowledged that some nodules and induration could persist between injections, yet added a reassuring note: “Despite the proportion of individuals who reported these reactions, people tend to tolerate them safely. Additionally, we find that over time, individuals get used to the injections and report fewer adverse events as time goes on.”
Resistance Considerations
Antimicrobial resistance to LEN was noted in 14 participants, primarily linked to poor adherence to their optimized background therapy. Ogbuagu discussed the need for careful management of these patients to avoid resistance development. “If we backtrack, we remember that many of the patients we included in the study had very high rates of resistance to antiretroviral drugs,” he stated. “Almost half had resistance to two or more drugs in all four main classes of antiretroviral drugs.”
He emphasized the importance of supporting adherence to the optimized background regimen, noting, “The vast majority of those who developed resistance were individuals who were poorly adherent.” His advice for clinicians is clear: “You really want to use lenacapavir in combination with at least one additional fully active agent where possible to mitigate the risk of emergent resistance.”
The results of the CAPELLA study have important implications for future treatment guidelines for HTE individuals with MDR HIV. “Lenacapavir is just a welcome addition to the repertoire of drugs for multi-drug resistant HIV,” Ogbuagu said. He highlighted the advantages of LEN as an injectable treatment that can be administered in a clinical setting: “Inherently, due to its mechanism of action and the way it's administered, we can support adherence for individuals because we give the injections in the clinic. This allows us to remind people of their appointments and keep track of their treatment history.”
Overall, the findings from the CAPELLA study reaffirm the efficacy and safety of LEN as a treatment option for HTE individuals with multidrug-resistant HIV. The long-term data support LEN’s role in achieving sustained virologic suppression, highlighting its potential as a critical component of HIV treatment regimens for patients with limited options.
With the integration of LEN into clinical practice, healthcare providers can enhance adherence and improve treatment outcomes for this challenging patient population. Ogbuagu’s insights underscore ongoing support and management to maximize the benefits of this innovative therapy in the fight against HIV.
