Gilead Sciences and GlaxoSmithKline will go head-to-head with rival versions of an improved class of HIV medicines, after clinical studies showed that Gilead’s new drug bictegravir was as effective as GSK’s product, reports Reuters Health.
Four late-stage studies from Gilead all met their goals, with bictegravir matching the efficacy of GSK’s established dolutegravir, which has been the cornerstone of the British group’s growing HIV business in recent years.
Both drugs are so-called integrase inhibitors, a type of medicine that has proved extremely effective at blocking the Aids virus. They are designed to be given alongside older antiretroviral therapies.
The report quotes Gilead as saying that drug combinations testing bictegravir had proved equally good, or “non-inferior”, to combinations using dolutegravir, as measured by their ability to suppress levels of HIV.
The news confirms a looming competitive threat to GSK’s important ViiV Healthcare business, but it also suggests the balance may not tip overwhelmingly in favour of Gilead. The report says the results are nonetheless a success for California-based Gilead, which Berenberg analysts said was likely to take a meaningful portion of growth in the HIV treatment market, with annual bictegravir sales reaching $3.8bn by 2020.
Gilead plans to apply this year for regulatory approval to sell its combination of bictegravir and emtricitabine/tenofovir alafenamide (FTC/TAF), with a submission in the US in the second quarter and Europe in the third quarter. And if Gilead uses a priority voucher at the US Food and Drug Administration, it could launch in the US market in the first quarter of 2018, some industry analysts said.
The report says for a long time Gilead has dominated the HIV market but GSK fought back strongly with dolutegravir, which has been a star performer recently. Now Gilead is hoping to reaffirm its dominance with its new three-drug combination based around bictegravir. GSK, meanwhile, is working on a two-drug treatment regimen.
Two of Gilead’s studies tested its combination against a regimen containing GSK’s dolutegravir in previously untreated patients. The other two trials involved patients who were already on HIV therapies, one of which including GSK’s dolutegravir, but were switched to the Gilead combination.
According to the report, data showed the Gilead combination was as effective and also well tolerated. No patients discontinued treatment due to kidney problems, a common side effect seen with HIV treatments.
Antiretroviral therapy has turned HIV from a death sentence into a manageable condition but patients need to stay on treatment for life, so there is a growing focus on making medication as well-tolerated as possible, the report says.
Gilead Sciences has announced that four Phase 3 studies evaluating a fixed-dose combination of bictegravir (50mg) (BIC), a novel investigational integrase strand transfer inhibitor (INSTI), and emtricitabine/tenofovir alafenamide (200/25mg) (FTC/TAF) for the treatment of HIV-1 infection met their primary objectives of non-inferiority, reports Business Wire. Three of the ongoing studies are designed to explore the efficacy and safety of BIC/FTC/TAF compared to regimens containing dolutegravir (50mg) (DTG) among treatment-naïve patients (Studies 1489 and 1490), and among virologically suppressed patients switching from an existing antiretroviral regimen (Study 1844). A fourth ongoing study in virologically suppressed patients compares switching to BIC/FTC/TAF versus remaining on a suppressive regimen of two nucleoside/nucleotide reverse transcriptase inhibitors and a boosted protease inhibitor (Study 1878).
“Since the approval of Viread 16 years ago, Gilead has continually worked to develop and improve treatments for people living with HIV. This investigational single tablet regimen brings together the potency of an integrase inhibitor, bictegravir, with the demonstrated efficacy and safety profile of the FTC/TAF backbone,” said Dr Norbert Bischofberger, executive vice president, research and development and chief scientific officer, Gilead Sciences. “Based on the results from these Phase 3 studies, the combination of bictegravir and FTC/TAF could represent an important advance in triple-therapy treatment for a broad range of HIV patients, and we look forward to submitting regulatory applications in the US and EU this year.”
Studies 1489 and 1490 are double-blind studies in which treatment-naïve patients (n=600 in each study) were randomized 1:1 to receive BIC/FTC/TAF and abacavir/dolutegravir/lamivudine (600/50/300mg) (ABC/DTG/3TC) (Study 1489) or DTG+FTC/TAF (Study 1490). The primary endpoint is proportion of patients with HIV-1 RNA levels <50 copies/mL at Week 48, and the lower bound of the 95% CI for non-inferiority is 12%. The studies remain blinded through 144 weeks.
In study 1,844, patients (n=520) who were virologically suppressed (HIV-1 RNA levels <50 copies/mL) on a regimen of ABC/DTG/3TC or DTG+ABC/3TC were randomized 1:1 to stay on their existing regimen or switch to BIC/FTC/TAF in a blinded manner. Study 1878 is an open-label study in which patients (n=520) who were virologically suppressed on a boosted protease inhibitor of darunavir (800mg) or atazanavir (300mg) plus a nucleoside/nucleotide backbone of ABC/3TC or emtricitabine/tenofovir disoproxil fumarate (200/300mg) were randomized 1:1 to either maintain their current regimen or switch to BIC/FTC/TAF. The primary endpoint in these studies is the proportion of patients with HIV RNA ≥50 copies/mL at Week 48, and the lower bound of the 95% CI for non-inferiority is 4%. Both studies were randomised through 48 weeks, after which point patients continuing in the studies enter an open-label extension receiving BIC/FTC/TAF.
BIC/FTC/TAF met the definition of non-inferiority in all four studies, with comparable proportions of patients having HIV-1 RNA <50 copies/mL (Studies 1489 and 1490) and HIV-1 RNA ≥50 copies/mL (Studies 1844 and 1878). In all studies BIC/FTC/TAF was well tolerated and no patients discontinued study medication due to renal events. No patients randomized to the bictegravir or dolutegravir arms developed treatment-emergent resistance. One patient randomised to the protease inhibitor arm in Study 1878 developed an abacavir resistance mutation (L74V).
Gilead plans to submit data from these Phase 3 studies for presentations at scientific conferences in 2017.
Bictegravir in combination with FTC/TAF as a single tablet regimen is an investigational treatment that has not been determined to be safe or efficacious.
GSK and ViiV Healthcare have, meanwhile, announced regulatory submissions to the European Medicines Agency (EMA) and US Food and Drug Administration (FDA) for a single-tablet, two-drug regimen of dolutegravir (Tivicay, ViiV Healthcare) and rilpivirine (Edurant, Janssen Sciences Ireland UC) for the maintenance treatment of HIV-1 infection.
The submissions are based on the SWORD studies that included more than one thousand patients who previously achieved viral suppression on a three- or four-drug (integrase inhibitor, non-nucleoside reverse transcriptase inhibitor, or protease inhibitor-based) antiretroviral regimen. The results of these studies were presented at the 2017 Conference on Retroviruses and Opportunistic Infections (CROI) in February.
A recently acquired priority review voucher was submitted to the FDA along with the dolutegravir and rilpivirine 2-drug regimen New Drug Application (NDA). Under the Prescription Drug User Fee Act, the anticipated target action date is six months after receipt of the application by the FDA. The $130m cost of the voucher will be reported as an R&D expense in GSK’s Q2 2017 Adjusted results.
Use of dolutegravir and rilpivirine as a two-drug regimen for HIV-1 maintenance therapy is investigational and not approved anywhere in the world.
Deborah Waterhouse, CEO ViiV Healthcare said, “As people living with HIV plan their lives, there is a need for new options to best manage their lifelong treatment. At ViiV Healthcare, we are not only developing potential new medicines to treat and prevent HIV infection, we are challenging the traditional HIV treatment paradigm to develop new treatment regimens. We look forward to working with regulatory authorities to bring this new single tablet, two-drug regimen to appropriate people living with HIV.”
Dr John C Pottage, Jr, chief scientific and medical officer, ViiV Healthcare, commented, “Traditionally, we have used a regimen of three or more drugs to maintain HIV viral suppression, but to best serve people living with HIV we must always question the status quo. We believed that dolutegravir would have the right profile to be a core agent in a two-drug regimen. Data from the SWORD studies supported our hypothesis that a two-drug regimen of dolutegravir and rilpivirine could maintain viral suppression and these regulatory submissions mark what may be a step change in HIV treatment. We are grateful to the study participants and clinicians who have contributed so much to making these submissions possible.”