Gilead's Biktarvy Approval Heightens HIV Competition With ViiV

Gilead hopes Biktarvy will enable it to win market share away from ViiV's dolutegravir-containing regimens, but ViiV filed a patent infringement case within hours of the US FDA approval of Gilead's new combo.

Gilead Sciences Inc. has been waiting for its new daily fixed-dose combination therapy for HIV, now known as Biktarvy, to provide new ammunition in its battle for HIV market share against ViiV Healthcare. But the competition wasted no time striking back with a patent infringement suit.

The US FDA's Feb. 7 approval of Biktarvy (BIC/F/TAF) – consisting of the novel integrase inhibitor bictegravir, the second-generation nucleotide reverse transcriptase inhibitor TAF (tenofovir alafenamide) and the older nucleoside reverse transcriptase inhibitor emtricitabine – gives Gilead a direct competitor against ViiV's Triumeq, which consists of the integrase inhibitor dolutegravir, the reverse transcriptase inhibitor abacavir and the nucleoside analogue reverse transcriptase inhibitor lamivudine. It could also enable Gilead to win market share in patients currently taking Tivicay (dolutegravir) as part of a non-proprietary combo including Gilead doublets such as Truvada (emtricitabine/tenofovir disoproxil fumarate (TDF) or Descovy (emtricitabine/TAF).

Within roughly two hours of the announcement of Biktarvy's US approval, ViiV issued a news release stating that it had filed patent infringement litigation in the US and Canada against Gilead asserting that bictegravir infringes ViiV's patents for dolutegravir "and many other compounds that include dolutegravir's unique chemical scaffold." The complaint asserts that similarities between bictegravir and dolutegravir suggest that Gilead simply copied the ViiV drug.

On Gilead's fourth quarter and full year 2017 earnings call Feb. 6, Chief Scientific Officer Norbert Bischofberger highlighted the imminent approval of Biktarvy, noting that the combo demonstrated non-inferiority against established HIV regimens in both treatment-naïve patients and those virally suppressed on other regimens. (Also see "Gilead's CAR-T Therapy Yescarta Slowly Getting Off The Ground" - Scrip, 6 Feb, 2018.)

"BIC/F/TAF met its primary objective of non-inferiority at 48 weeks across all four [Phase III] studies and no participants failed BIC/F/TAF for treatment-emergent virological resistance," the exec said. "Additional clinical trials of BIC/F/TAF are ongoing, including a dedicated study in women as well as a study in adolescents living with HIV."

Safety Advantages Anticipated

Bischofberger said the combo should enjoy multiple advantages compared to its competition, including the fact that no treatment resistance was observed over the four pivotal studies and that it offers a favorable bone and renal safety profile compared to Tivicay-containing regimens. (Also see "Gilead's Bictegravir Data Could Mean Continued HIV Sector Dominance" - Scrip, 15 Feb, 2017.) He pointed out that roughly half of US HIV-infected patients are now over the age of 50, making these safety factors increasingly important.

Biktarvy is approved specifically to treat HIV-1-infected patients with no prior treatment history with antiretroviral therapy or as replacement treatment for infected patients who are virologically suppressed on a stable regimen taken for at least three months with no history of treatment failure or of substitutions associated with resistance to any of the product's three components. The approval carries a requirement for three post-marketing studies – one in treatment-experienced HIV patients between the ages of 2 and 18, one in treatment-naïve patients at least four weeks old and weighing between 4 kg and 12 kg, and one to assess safety and pharmacokinetics in neonates either HIV-infected or exposed to and at high risk for the virus.

The combination also is under review by the European Medicines Agency, with Gilead anticipating approval during the third quarter of 2018.

On ViiV-parent GlaxoSmithKline PLC's quarterly earnings call Feb. 7, the firm reported that the Tivicay/Triumeq franchise generated £3.86bn (more than $5.3bn) in revenue during 2017, making HIV a key growth driver for GSK. (Also see "ViiV's Two-Drug HIV Tablet Juluca Is Disruptive, Yet Uptake May Be Slow" - Scrip, 22 Nov, 2017.) GSK is the majority owner in ViiV, a joint venture shared with Pfizer Inc. and Shionogi & Co. Ltd.

Asked about the potential for patients to switch over to Biktarvy, ViiV Chief Strategy Officer David Redfern noted that the Gilead regimen only demonstrated non-inferiority to Tivicay-containing regimens in its Phase III program, and in some cases the Tivicay regimens were numerically if not statistically significantly superior.

"I think HIV is an increasingly chronic disease," Redfern said. "Patients who are well tolerated, well controlled, typically now visit their physicians probably only once every six months or so. So [treatment is] relatively conservative. … When you look at the clinical data, we don't see any good medical reason why patients well controlled and well treated on dolutegravir today should switch to something else."

During Gilead's Feb. 6 earnings call, CEO John Milligan was asked if he anticipated ViiV lowering prices of Tivicay and/or Triumeq as a strategy for maintaining market share. "That has never happened in the field of HIV, but I don't know what even GSK are planning," he said. "That's all I can tell you."

Bischofberger said one factor that might spur rapid adoption of Biktarvy is how quickly new Gilead HIV combos comprising TAF – such as Genvoya (elvitegravir/emtricitabine/TAF) – were incorporated into US HIV treatment guidelines. While cautioning that Biktarvy would require its own adoption process, he noted "it used to take a long time many years ago, but in the case of Genvoya it took exactly two weeks [after FDA approval]. So it's not true anymore that it takes a long time for [a new therapy] to get on the guidelines."

In a Feb. 7 note issued before the approval, BMO Capital Markets analyst Ian Somaiya said Biktarvy likely would play a key role in protecting Gilead's roughly $14bn HIV franchise and help the business grow to a projected $16.6bn in sales in 2021. (Also see "Is Gilead Vulnerable to ViiV As It Nears End Of HIV R&D Activity?" - Scrip, 3 Nov, 2016.) Biktarvy approval and success are crucial for Gilead, he pointed out, because the company's Truvada and Atripla (efavirenz/emtricitabine/TDF) lose US patent protection in 2021, followed by Descovy in 2022, and Odefsey (emtricitabine/rilpivirine/TAF) and Complera (emtricitabine/rilpivirine/TDF) in 2023.

Prospects For Gaining Market Share

In the near-term, Biktarvy seems best positioned to siphon market share from patients who take Tivicay with Truvada or Descovy due to the convenience of a single-tablet regimen and the renal safety benefit Gilead claims for bictegravir. Such patients comprise an estimated 8% of the US HIV treatment market, Somaiya wrote, while Triumeq patients make up 8%-9% of the US patient base. Shifting patients over to Biktarvy from Gilead's own Genvoya offers another 11%-12% of the market to target, he added.

"Collectively, between 25% and 30% of the HIV market (based on weekly IMS scripts) could be immediately accessible to BIC/F/TAF," the analyst said.

In a note on the approval, Jefferies analyst Michael Yee commented that Biktarvy's label appears clean, with safety and precautions language largely similar to that in the Genvoya label. "Launch should be relatively quick and drive the HIV franchise as a single-digit growth business," he wrote Feb. 7.

Yee added that Gilead believes Biktarvy's launch could outperform that of Genvoya, which realized net sales of $966m during its first 12 months on the market. Jefferies models first-year sales of $850m, although Yee conceded that estimate is conservative.