GlaxoSmithKline's new HIV dual-drug regimen meets phase 3 goal, but analysts want more

GlaxoSmithKline’s ViiV Healthcare already has Juluca, the first complete two-drug HIV therapy, for patients who are virally suppressed. Now, it has new data to back its dual-drug expansion into treatment-naïve patients, but analysts want to see more data before giving their definite thumbs-up.

In two phase 3 studies on altogether about 1,400 people living with HIV, dolutegravir (Tivicay) and lamivudine (Epivir) showed noninferiority at successfully controlling HIV viral load compared to a standard triplet that pairs dolutegravir with Gilead’s Truvada (tenofovir and emtricitabine), ViiV reported Thursday.

“The GEMINI studies … affirm our two-drug regimen strategy, and reinforce our belief that many patients can control their disease with two drugs instead of three or more,” said John Pottage, M.D., ViiV’s chief scientific and medical officer, in a statement.

ViiV plans to file for regulatory approvals later this year based on the 48-week data, and will follow patients up for 96 weeks.

The studies met their primary endpoint, but analysts still have questions they hope to be answered from the full data, especially about HIV drug resistance.

“Going into the readout, the biggest question was around resistance potential since there will only be a single background [nucleoside reverse transcriptase inhibitor],” wrote Evercore ISI’s Umer Raffat in a note to investors.

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ViiV points out in the release that “[n]o patient who experienced virologic failure in either treatment arm developed treatment-emergent resistance.” But because many clinicians worry that noncompliant patients on dual regimen might be more likely to develop resistance vs. those on triple regimen, Raffat said he wants to look at the resistance profile of patients who weren’t 100% compliant in the studies.

Jefferies analyst Michael Yee shared similar curiosity. Noting resistance might not be a problem in the first year, Yee said in his note that “the key according to doctors is whether resistance could develop over time,” especially as real-world patient compliance won’t be the same as in a controlled clinical trial.

Management has previously expressed optimism when asked of the same question, and they hope the full GEMINI readouts, when finally presented, could help put the resistance doubt to rest.

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“We don't believe that there will be [a greater likelihood of resistance in a two-drug regimen versus a three-drug regimen] on the basis of the fact that dolutegravir has a very high barrier to resistance and that it has been very effective in the studies thus far of two-drug regimens,” ViiV’s head of clinical development, Kim Smith, M.D., said during an Evercore event last November.

The news come at an important time for GSK’s HIV business, currently under pressure from Gilead’s three-drug regimen Biktarvy, which is meant for both treatment-naïve and switch-over patients. For the first quarter, despite a group-wide 14% sales growth, Tivicay and its sister combo drug Triumeq posted sales slightly below analysts’ estimate. During the first-quarter call, Glaxo Chief Strategy Officer David Redfern assured investors that dolutegravir was still leading the core-agent market with a share of more than 28%.

Next up on ViiV’s dual-drug development agenda? It expects to announce later this year phase 3 data from two studies that examine cabotegravir and rilpivirine as a monthly regimen, with eyes on it eventually being a bimonthly injectable.