ViiV Healthcare’s success with monthly combo HIV med making Gilead sweat over its HIV franchise. After World Cup fiasco, England chasing California in $$$$/rep race.

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The News:

GlaxoSmithKline PLC’s (London) ViiV Healthcare unit now has results to support a two-drug monthly injection co-developed with Johnson & Johnson (New Brunswick NJ) as it pushes ahead with its ambition for two-drug HIV therapies to challenge archrival Gilead Sciences Inc. (Foster City CA).

The injection combines ViiV’s investigational integrase inhibitor cabotegravir with Janssen’s Edurant (rilpivirine), which is already paired with Tivicay (dolutegravir) in Juluca, the world’s first complete two-drug therapy, says FiercePharma.

In a Phase 3 trial called Atlas on patients already virally suppressed, the monthly regimen showed similar efficacy compared with a three-drug therapy at week 48, the two companies reported. If approved, this regimen would give people living with HIV one month between each dose of antiretroviral therapy, changing HIV treatment from “365 dosing days per year, to just 12,” said John Pottage, MD, ViiV’s chief scientific and medical officer, in a statement.

Detailed data from the Atlas study will be presented later, and another study called Flair that’s testing previously untreated patients will deliver top-line results soon. In that study, patients start with traditional triplet treatment and then switch to the monthly injectable. GSK is also testing the regimen as a bimonthly injection in Phase 3.

GSK’s strategy is to rewrite the HIV care textbook and establish two-drug therapies as the new standard, because exposing patients to fewer drugs could mean that fewer side effects would develop over time, during treatment that can last for decades.

The Atlas readout followed two closely watched results unveiled last month from oral two-drug regimens taken daily. In one study, a combo of Tivicay and Epivir (pdf) (lamivudine) matched a three-drug regimen of Tivicay plus Gilead’s Truvada (tenofovir and emtricitabine) at containing treatment-naïve patients’ viral load through a year of therapy. No treatment-related viral resistance manifested in the two-drug arm.

Steve’s Take:

 Now this is exciting. England vs. California. And I’m not talking about soccer (okay, football), cricket or skateboarding.

ViiV Healthcare has shown its monthly two-drug HIV treatment works as well as a daily three-drug treatment, which could help reduce the total number of drugs taken by patients.

Earlier this year, ViiV reported positive Phase III results for two other HIV treatments that use different two-drug combinations given daily. One of these, called Juluca, recently received approval in the US and Europe, making it the first dual HIV treatment to get market authorization.

Not widely reported, however, is that Gilead also obtained positive Phase 3 results for its own two-drug HIV therapy this year and is seeking regulatory approval from the EMA and FDA, says LaBiotech. ViiV is suing Gilead over patent infringement, claiming one of the drugs Gilead uses in its treatments is too similar to ViiV’s drug dulotegravir.

HIV treatments have come a long way since the disease was discovered in the 1980s. But while reducing the number of drugs patients require is an important step forward, biotechs should ultimately strive to find a functional cure, which some believe could become available within the next decade.

Steve's Take: Finally, a functional cure for #HIV could become available within the next decade Click To Tweet

But as analysts have said, to challenge the three-drug market currently led by Gilead, GSK still needs more data to quell concerns about potential long-term resistance, especially in the real world. As new data on Juluca showed, 89% of participants who were on the two-drug therapy for 100 weeks maintained viral suppression, below the 93% who switched to it for only a year. In addition, three patients who didn’t take their drugs as directed developed Edurant-specific resistance.

While Pottage at that time said resistance development was normal in clinical trials that long, doubters might see it as evidence of the approach’s lower potency in the long run.

Thanks to Tivicay-based drugs, GSK’s HIV franchise registered 11% sales growth at constant exchange rates during the second quarter, to reach £1.19 billion ($1.5 billion), with £24 million of that from Juluca. According to CEO Emma Walmsley, speaking on the earnings call, Juluca now has a 3.7% share of new-to-brand prescriptions; total weekly scripts in the US exceed a thousand.

GSK’s current HIV growth plan faces a powerful rival in Gilead’s just-approved Biktarvy, a three-drug regimen. In the second quarter—the first full quarter it was on the market—Biktarvy sold $183 million in the US.

“Based on its current trajectory, we anticipate that Biktarvy will become the No.1 single tablet regimen for treatment-naïve patients and will overtake Genvoya as the most successful launch in HIV history,” said CFO Robin Washington on Gilead’s second-quarter earnings call.

According to Washington, a quarter of switch-overs to Biktarvy came from Tivicay-based drugs.

Bottom Line:

“ViiV has the potential to differentiate itself from current and future competitors, while effectively competing head-to-head with Gilead,” according to James Mather, pharma analyst at the data and analytics company, GlobalData. “The fact that Juluca is not available for treatment-naïve HIV-1 patients limits its potential patient share, particularly in the face of Gilead’s latest STR, Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide) which received approval for use in treatment-naïve and virally-suppressed patients earlier this year.”

GlobalData believes that the pricing of dolutegravir/lamivudine could be an important factor in the uptake of this two-drug STR following its launch, ThePharmaLetter notes. A price higher than ViiV’s other STRs, Juluca and Triumeq (abacavir/dolutegravir/lamivudine), could be justified, as dolutegravir/lamivudine has some distinct advantages over both products–its label will likely include treatment-naïve patients, and it is an efficacious alternative for patients who cannot tolerate side effects associated with sustained abacavir use.

Competition from Biktarvy, along with widespread availability of generic lamivudine, might be the major limiting factor on what ViiV can charge for the new STR, GlobalData observes.

Mather adds: “From a larger competitive landscape standpoint, these positive results for a two-drug ART regimen strengthens the outlook for ViiV’s portfolio, particularly when considered alongside its long-acting, NRTI-free combination of cabotegravir/rilpivirine, which is also in Phase 3 trials.”

GlobalData expects the combined sales of dolutegravir/lamivudine, cabotegravir/rilpivirine, and Juluca to exceed $7 billion across the USA, France, Germany, Italy, Spain, UK, Japan, Brazil and China by 2025.

“The range of two-drug regimens being developed means that ViiV has the potential to differentiate itself from current and future competitors, while also effectively competing head-to-head with Gilead,” Mather added.

After the World Cup fiasco, England could use a “win” in the HIV games. The stakes are monumental, and not just dollar-wise. There’s also the reputational “win” going forward with its science prowess in this evolving space. And the competition is a tough-nose striker from lowly-little Foster City in California’s earthquake capital. Certainly not in the same class as a Batistuta, Ruud van Nistelrooy, and Ronaldo. But who is?

Should be quite a match, though.

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