Islatravir

Some 20 years after helping introduce the first once-daily single tablet HIV regimen, Gilead Sciences has crossed the regulatory finish line with a new oral treatment option in the U.S. The FDA approval of Bixlenvo tees up a new HIV treatment option for virologically suppressed adults, including those on complex drug regimens for whom other single tablet options are a poor match. The daily tablet weds the tried-and-true integrase strand transfer inhibitor bictegravir with Gilead’s more recent capsid inhibitor lenacapavir. The tablet marks a fusion of two eras of Gilead’s history. Bictegravir is one of three ingredients in current HIV standard-of-care Biktarvy, which has defined much of Gilead’s recent trajectory combatting the virus. For its part, lenacapavir—first approved as Sunlenca as part of an HIV treatment option in 2022 and then as Yeztugo as a twice-yearly PrEP injection last summer—signals where the company is headed next with its HIV franchise. In a statement Thursday, Gilead CEO Daniel O’Day framed the approval as meaningful to those HIV patients wanting to switch up or simplify their treatment. “Our goal at Gilead is to provide multiple options for HIV treatment and prevention,” he said. The green light was backed up by data from Gilead’s late-stage Artistry-1 and -2 studies, which sought to enroll a broad spectrum of people living with HIV. Artistry-1 specifically looked at Bixlenvo in patients presently managing their HIV with complex multi-tablet regimens, due to factors like acquired drug resistance, tolerance issues or drug interactions. Artistry-2, on the other hand, pitted Gilead’s new doublet pill against its own Biktarvy, where it proved non-inferior in maintaining virologic suppression in patients who switched. In both studies, the percentage of patients with HIV-1 RNA levels ≥50 copies/mL—a standard measure of detectable HIV—at week 48 was used as the primary endpoint. Patients who switch to Bixlenvo will need to first take a two-day loading dose of Sunlenca alongside the new doublet before Bixlenvo can be taken by itself. In framing the specific patients for whom Bixlenvo could most benefit, Gilead’s SVP of clinical development and head of virology, Jared Baeten, M.D., told Fierce earlier this year that “[t]his is a medicine, really, that is addressing some of the challenges of aging with HIV.” The median participant age was 60 years in Aristry-1, making it the “oldest study population in a phase 3 registrational trial for HIV-1 treatment to date,” Gilead said in its approval announcement. Those older patients may be especially susceptible to drug resistance or other intolerance based on years of experience using earlier, “less robust therapies of the past,” Baeten said in an interview around the tablet’s pivotal trial results in February. Meanwhile, Baeten told Fierce at the time that lenacapavir is at the heart of the California drugmaker’s current development efforts, noting that Gilead is hoping to offer an ever-widening armamentarium of HIV treatment and prevention options across formulations and dosing timelines. Part and parcel to those efforts, Gilead has also set the goal to strike out on seven new HIV launches by the end of 2033. The company, together with its partner Merck & Co., recently detailed positive phase 3 results for what could be the first complete weekly pill for the treatment of HIV, combining lenacapavir with the New Jersey pharma’s nucleoside reverse transcriptase translocation inhibitor, islatravir.

Years of litigation surrounding Gilead Sciences’ tenofivor-based HIV treatments have come to an end, with the California Supreme Court taking Gilead’s side in a ruling that sets a key precedent for innovative drugmakers. After hearing arguments earlier this summer, the court ruled (PDF) in a 6-1 decision to dismiss thousands of negligence claims against Gilead concerning its older tenofovir disoproxil fumarate (TDF)-based medicine, such as Viread, Truvada and others, as well as its newer products made with tenofovir alafenamide fumarate (TAF), which is in the company's Biktarvy and Descovy. Patients claimed that they would have switched to the safer alternative drug if Gilead hadn’t “unreasonably delayed” bringing it to market, while Gilead maintained that a speedy development and commercialization timeline for a newer product falls outside of its duty of care, regardless of safety profile. With its Aug. 3 ruling, the California Supreme Court agrees with the latter, explaining that imposing a duty of care in this situation would place “extraordinary burdens” on drug manufacturers and risk “distorting research priorities and chilling pharmaceutical innovation in ways that may ultimately undermine, rather than advance, public health and safety,” Justice Joshua Groben wrote in his majority opinion. “What today’s decision declines to do is recognize, for the first time anywhere, sweeping liability for injuries caused by a concededly nondefective drug because the manufacturer allegedly failed to make a different drug available sooner,” Groban continued. “Imposing such liability would create substantial burdens and would risk adverse consequences for pharmaceutical innovation, public health, and patient safety.” For years, plaintiffs have argued that although Gilead's TDF-based medicines are effective in treating HIV, the risk of adverse events such as skeletal and kidney damage should have made the company act faster in developing its safer, lower-dose TAF drug candidate. Several lawsuits have accused Gilead of purposely shelving its TAF development for years in order to drum up continued sales of its earlier drugs before eventually launching the newer medicines, knowingly leaving patients suffering from bone and kidney damage in the meantime. Crucially, the plaintiffs’ acknowledgement that Gilead’s TDF medicines are not defective is the key aspect that creates the unique “duty to innovate” argument that the case hinges on. Gilead has long contended that plaintiffs cannot seek compensation for harm caused by a product that is not proven defective and that it had no duty to disclose information related to a potential alternative treatment when it had not yet been approved. The company emphasized the sweeping stakes of the case when the California appeals court approved the plaintiffs negligence claim in 2024, with Gilead warning of “widespread, negative consequences across all fields of innovation and manufacturing,” a spokesperson told Fierce Pharma at the time. The case ultimately came to question if drugmakers like Gilead have a “duty to innovative” by quickly developing safer or better products. To Gilead’s point, dozens of amicus briefs across industries flooded in to support Gilead and its argument that manufacturers do not have a “duty to innovate,” with other top drugmakers plus those in the automobile and consumer goods sectors such as Lyft and Uber urging the California Supreme Court to reverse course set by the lower courts. Ultimately, the court concluded that drug makers “do not owe a duty of care to users of a non-defective drug when making decisions about whether and when to commercialize an allegedly safer alternative drug,” Groban wrote. The vote, however, wasn’t unanimous, with Justice Kelli Evans, arguing in her dissenting opinion that the decision offers “sweeping immunity” for drugmakers to make products “without accounting for the risk of harm to consumers like plaintiffs here, who are held captive when a drug is both lifesaving and subject to exclusive manufacturing rights.” Groben disagrees, citing the standard legal claims that drugmakers still remain subject to when it comes to FDA-approved products. Gilead called the ruling a victory for all those working to develop improved medical treatments and new medicines,” the company said in a statement , adding that the court’s decision “supports American innovation, allowing companies to continue pursuing breakthroughs for patients and consumers.” “Gilead is proud to have developed innovative, life-saving medicines that continue to be used by millions worldwide to prevent and treat HIV,” the company continued. “We remain committed to ending the HIV epidemic through scientific innovation and a focus on the needs of people with HIV.” In closing out the TDF/TAF litigation chapter, Gilead is simultaneously moving to a new era of HIV treatment altogether with its lenacapavir, a capsid inhibitor that’s separate from the tenofovir-based products of the past. After first hitting the market as a treatment for multi-drug resistant HIV in 2022, the long-acting drug made waves with its first pre-exposure prophylaxis approval last year. Most recently, lenacapavir is angling to be apart of the first complete once-weekly HIV pill in a combination with Merck’s islatravir.