GSK's Dovato matches Gilead's HIV juggernaut Biktarvy with less weight gain in Spanish trial

In HIV treatment, Gilead Sciences’ popular Biktarvy serves as a benchmark for newer drugs to overcome. In a new head-to-head study, GSK’s two-drug regimen Dovato showed comparable antiviral efficacy to the Gilead triplet.

The phase 4 study, coded PASO DOBLE, found that among Spanish patients who already had their HIV under control, switching to Dovato worked as well as to Biktarvy in maintaining viral suppression after 48 weeks of treatment.

At the time of the analysis, 2.2% of 277 Dovato takers had snapshot viral RNA at or above 50 copies/mL in their blood samples, compared with 0.7% of 276 patients on Biktarvy. The 1.4-percentage-point difference met the trial’s prespecified non-inferiority margin of 4%. The results will be presented at the 25th International AIDS Conference in Munich, Germany.

The study was sponsored by the SEIMC-GeSIDA Foundation and conducted across 30 sites across Spain. It recruited virologically suppressed patients who were taking multi-tablet regimens, or using older, more toxic drugs such as efavirenz or tenofovir disoproxil fumarate (TDF). Both Dovato and Biktarvy are given as a single pill per day.

In a key secondary endpoint, the trial found that Biktarvy takers experienced significantly more weight gain than their Dovato-receiving counterparts. The adjusted mean change in body weight was 1.81kg (3.99lbs) and 0.89kg (1.96lbs) for the two groups, respectively, during the 48 weeks.

The proportion of individuals who experienced weight gain of more than 5% was significantly higher for Biktarvy, at 29.9%, than it was for Dovato, at 20%.

Further, the weight-gain difference appeared to be more pronounced when a patient switched from a TDF-containing regimen. Among those patients, 40.7% of individuals in the Biktarvy arm had more than 5% weight gain, versus 19.5% for Dovato. Biktarvy contains the newer, less toxic tenofovir alafenamide fumarate (TAF), while Dovato doesn’t use tenofovir.

“This is a meaningful outcome, as treatment-related weight gain is an important topic for many people living with HIV,” Harmony Garges, M.D., chief medical officer at GSK’s ViiV Healthcare, said in a statement.

Weight gain is a known effect associated with certain HIV meds, including integrase inhibitors such as dolutegravir used in Dovato and bictegravir used in Biktarvy. It’s also an issue with TAF, with the combination of the two mechanisms known to be more likely to cause weight increases.

“The HIV treatment regimens that are commonly prescribed today are all highly effective, which makes it critical that we study the impact of these therapies beyond just viral suppression,” Esteban Martínez, M.D., Ph.D., lead investigator of the PASO DOBLE trial, added in a statement.

The exact mechanisms for weight gain remain unclear. Various hypotheses have explained the phenomenon as a result of immune recovery or an improved appetite thanks to the newer drugs’ tolerability advances. But no conclusion has been reached.

As Martínez duly noted, HIV medications are already highly efficacious. So for next-generation therapies, companies have been focusing on their features beyond efficacy, including reducing side effects or dosing frequency.

Dovato marks GSK’s effort in the first category. By slashing the number of drug ingredients from three to two, Dovato was designed to avoid some longer-term toxicities for patients.

The key competition between GSK and Gilead now lies in the development of longer-acting regimens based on two-drug constructs. GSK has attracted some followers with its bimonthly injection Cabenuva. But the British pharma has acknowledged that even longer dosing intervals will be necessary to make a bigger impact. Gilead is slightly ahead with its twice-a-year drug Sunlenca and is actively looking to develop a complete regimen based on the capsid inhibitor.