GlaxoSmithKline launches full-on assault on Gilead with 2-drug HIV regimen data

GlaxoSmithKline's quest to trounce three-drug HIV therapies with its own two-drug regimens just got a boost. In detailed data from two trials, a combination of Tivicay (dolutegravir) and Epivir (lamivudine) squashed viral loads just as well as standard triple therapy did.

The two studies, from GSK's Gemini program, encompassed 1,400 previously untreated patients and pitted the Tivicay/Epivir combo against Tivicay plus Gilead Sciences' Truvada (tenofovir and emtricitabine). Both combos pushed HIV viral load below 50 copies/mL at week 48, with 91% of the GSK duo's patients reaching that level compared 93% of those taking Tivicay along with Gilead’s Truvada (tenofovir and emtricitabine), ViiV revealed at the International AIDS Conference in Amsterdam.

The new data add to GSK's case for a new HIV treatment paradigm based on cheaper two-drug regimens that carry less side effects—and that can challenge Gilead’s market-leading position in HIV.

It was a key milestone for the pair, because the viral load in new patients is usually quite high, and “you have a higher mountain to climb,” John Pottage, ViiV’s chief scientific and medical officer, told FiercePharma. And the new data shows trial patients with the highest viral loads—over 100,000 copies/mL, seen in 20% of the study participants—saw results consistent with those in patients with fewer copies.

The results held true in the 10% of trial patients who were 50 years and older, too, Pottage said. Though the triplet slightly topped the two-drug regimen, the difference wasn't statistically significant, he said.

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But climbing over that mountain is just one step for any HIV treatment, because patients will likely live with it for decades. Since ViiV floated the two-drug idea, analysts have been closely watching ViiV's data for emerging treatment resistance in the dual-drug patients. The worry is that the regimen wouldn't be strong enough to control the virus and that patients who don't take their meds as prescribed could develop resistance more easily than those on traditional triplet combos.

In the GEMINI studies, rates of virologic failure—where the antiretroviral therapy failed to suppress the virus— were within 1% across all arms, and no treatment-emergent resistance occurred. “You’ll always have virologic failure in studies because people may miss doses, [but] the incidence is very low [in the Gemini studies],” said Pottage. “And even when it did happen, nothing happened to the virus, it’s still susceptible to [the DTG+3TC therapy].”

Analysts, however, including Evercore ISI’s Umer Raffat and Jefferies’ Michael Yee, have previously noted that resistance-related viral mutations might not be a problem in the first year, but could happen over time.

Evidence might be found in 100-week data ViiV just released on Juluca (dolutegravir and rilpivirine), GSK's first-ever complete two-drug therapy, approved only for patients already virally suppressed. In pooled data from two of its Sword studies, 89% of participants on Juluca for 100 weeks maintained viral suppression, four percentage points below the 93% of patients who switched to it for just a year. Among 513 subjects on Juluca through week 100, three nonadherent patients developed mutations for resistance to rilpivirine. One of them had pre-existing mutations at baseline.

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Some might see the emergence of resistance as an alarming sign, but Pottage stressed that the numbers are very small. “It is what you would expect in any clinical trial at this time point, even with three-drug regimens,” he said.

“This 100-week data should provide physicians with further confidence that they may be able to reduce the number of antiretroviral drugs required to effectively maintain virologic suppression in their patient’s HIV,” said Pottage in a statement.

To truly change the HIV treatment paradigm to a two-drug approach, longer-term data will likely be needed. Pottage admitted some physicians will still want to see more stats, and analysts said that initial skepticism could lead to a slow ramp-up for Juluca and DTG+3TC. ViiV will file for regulatory approvals based on the 48-week data, but will carry on the Gemini research for up to three years in the hope of proving the duo's efficacy is durable.

Gilead currently holds about 52% of the HIV market, while GSK has about 22%. GSK is betting on its dolutegravir-based therapies could outdo Gilead’s bictegravir combos. But at least for now, Gilead’s new drug Biktarvy (BIC/FTC/TAF) is pressing ahead toward the $6 billion analysts pegged for its peak sales, while Triumeq and Tivicay sales for the first quarter were below analysts’ estimates.