GSK's ViiV, armed with long-term Dovato data, eyes 'tipping point' for 2-drug HIV regimen

Changing over two decades of treatment practice can be laborious. For ViiV Healthcare, the process involves delivering long-term data to prove its two-drug HIV regimens work just well as traditional triplets over time. Now, the GlaxoSmithKline subsidiary believes it has the results to boost confidence among doctors and move closer to a major growth boost.

After 144 weeks of treatment, ViiV’s Dovato was still as good as a three-drug regimen containing its own Tivicay and Gilead Sciences’ now generic Truvada at controlling HIV in previously untreated patients, according to data unveiled at the HIV Glasgow congress.

Specifically, in a pooled analysis of the Gemini 1 and 2 studies, 82% of Dovato patients maintained undetectable viral loads in their blood after 144 weeks, compared with 84% for those who got a three-drug cocktail.

Industry watchers have repeatedly expressed concerns over whether just two active ingredients would be able to suppress the virus over a long period of time. But in Gemini 1 & 2, just 1.7% of Dovato patients had two consecutive viral load rebounds and were therefore considered to have failed the treatment, while 1.3% of three-drug patients experienced the same.

Another fear is that resistant viral mutations could develop more easily for dual-drug regimens when patients don’t take their meds as directed. After 144 weeks, there was one case of a resistant mutation in more than 700 patients receiving Dovato. But Kimberly Smith, ViiV’s R&D chief, said the patient may have split up the regimen, taking only one of Dovato's component drugs, since patients in the Gemini studies took Dovato's Tivicay (dolutegravir) and lamivudine components separately.

“That’s why fixed-dose tablets are important, because they increase adherence and make sure that patients can’t split their medications,” she added.

RELATED: Can new Dovato data jump-start uptake of 2-drug HIV regimen? ViiV hopes so

ViiV has been churning out data to support its two-drug HIV regimens, but by the look of prescription figures, interest in the idea remains modest, especially when compared with the launch trajectory for Gilead’s market-leading Biktarvy. Despite two-year results and an expanded FDA label granted in August for patients who already have the virus under control using other drugs, Dovato’s total U.S. scripts over the past few weeks were only growing at a steady 5% month over month, according to IQVIA data cited by RBC Capital Markets.

The three-year data—which ViiV’s market research found is exactly the longevity analysis physicians want to see—on top of that new indication and inclusion in treatment guidelines, “will be a tipping point in terms of building confidence and driving growth for Dovato,” ViiV CEO Deborah Waterhouse said in a Monday interview.

Gilead, by contrast, is offering physicians another swap option with Biktarvy. But getting patients to move over from the Big Biotech's older blockbuster Genvoya and other three-antiretroviral regimens makes for a relatively easy switch, Waterhouse pointed out.

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“We’re trying to change the treatment paradigm,” she said. “For people with HIV, we’re trying to establish … the belief among physicians that you can actually keep the virus suppressed over the long term with two-drug regimens powered by dolutegravir and later cabotegravir at the core. We know it takes time.”

Right now, Dovato holds 3.2% U.S. share among newly diagnosed patients. Waterhouse isn't surprised by that relatively low rate since “if people are going to try a two-drug regimen, they’re probably going to try in switch first, get used to it, and then prescribe it for a person that’s newly diagnosed.”

In the switch market for patients who are already virologically suppressed, Dovato already boasts more than 10% share in the U.S., though Waterhouse acknowledged there was some off-label use before the official August FDA nod in that indication.

RELATED: GSK's ViiV touts 2-month HIV data as sister injection Cabenuva awaits FDA redemption

Acceptance of two-drug regimens is higher in Europe, with nearly 20% adoption among switchers in some territories. Waterhouse attributed the difference to two drivers: a belief that less is better, and drug cost. While pricing is not necessarily factored into physicians’ prescribing decisions in the U.S., studies of drug duos were initially undertaken because of their potential cost benefit over three-drug cocktails, Waterhouse noted.

Other than Dovato, ViiV also has Juluca, which is only allowed in patients for whom the virus is already under control. Together, these two drugs brought in sales of £367 million ($476 million) in the first half of 2020. Biktarvy’s haul totaled about seven times that number, at $3.30 billion.

ViiV’s long-acting injectable, Cabenuva—which combines ViiV’s cabotegravir with Johnson & Johnson’s rilpivirine (approved in tablet form as Edurant)—won its global-first nod in Canada in March. Having resolved the manufacturing issues flagged in an FDA complete response letter, ViiV resubmitted the drug in the U.S. in July and is now looking for a decision by Jan. 28, 2021.