Islatravir

Gilead’s Biktarvy has previously been approved by the US FDA as HIV treatment in both adult and paediatric (weighing at least 14kg) populations. Image Credit: Michael Vi / Shutterstock. Gilead Sciences has received a US Food and Drug Administration (FDA) approval for the label expansion of its human immunodeficiency virus -1 (HIV-1) fixed dose combination therapy, Biktarvy (bictegravir 50mg/emtricitabine 200mg/tenofovir alafenamide 25mg). The therapy is approved in pregnant patients in their second and third trimesters and up to 16 weeks following delivery (postpartum) with suppressed viral loads of HIV-1. The FDA first approved Biktarvy as a complete regimen for treating HIV-1 in adults who either have no antiretroviral treatment history or as a replacement for the current antiretroviral regimen in those who are virologically suppressed, in 2018. The FDA label expansion was based on the data from an open-label Phase Ib trial (study 5310). The single-arm study evaluated the pharmacokinetics, safety, and efficacy of Biktarvy in 32 pregnant patients with suppressed viral loads of HIV-1. All the participants maintained viral suppression during pregnancy and through 18 weeks postpartum, with lower plasma exposures observed during pregnancy compared to postpartum. All 29 newborn participants had negative or nondetectable HIV-1 polymerase chain reaction (PCR) results at birth and/or at four to eight weeks postbirth. In addition, the trial did not identify any new safety or tolerability concerns for people who use Biktarvy during pregnancy and postpartum. The overall incidence and types of adverse events observed were consistent with those expected for the population studied, as per Gilead. See Also: Accord BioPharma’s HERCESSI secures FDA approval Biktarvy is recommended as an alternative complete regimen for use in pregnancy and for people who are trying to conceive by the US Department of Health and Human Services (DHHS) perinatal guidelines. Biktarvy is a top revenue-generating therapy in Gilead’s portfolio and pulled in $2.9bn in sales in Q1 this year, as per the company’s financials. The sales for the therapy are expected to increase to $15.5bn in 2030, as per GlobalData analysis. GlobalData is the parent company of Pharmaceutical Technology . Another HIV therapy in Gilead’s portfolio is Sunlenca (lenacapavir), an FDA-approved multidrug-resistant HIV treatment . The company is evaluating Sunlenca in combination with Merck & Co’s islatravir as a long-acting HIV treatment for virologically suppressed people living with HIV.

The flurry of Trodelvy developments accentuates what Gilead CEO Dan O’Day called “a time of focused execution” at the California biotech. After a negative phase 3 readout, Gilead Sciences is taking a $2.4 billion impairment charge on Trodelvy, which serves as the cornerstone of the company’s solid tumor ambition. Gilead has cut the carrying value of Trodelvy to $3.5 billion in its first-quarter report, from $5.9 billion at the end of 2023, Chief Financial Officer Andrew Dickinson told investors during a call Thursday. The move comes after a January report of a phase 3 trial that the TROP2-directed antibody-drug conjugate failed to significantly extend the lives of patients with previously treated non-small cell lung cancer compared with chemotherapy. The bad news at that time caused a 10% slide in Gilead’s stock price. The write-off reflects a “smaller addressable market that Trodelvy could serve among second-line-plus metastatic non-small cell lung cancer patients, a delay in expected launch timing and associated competitive activity,” Dickinson said. Gilead remains confident that Trodelvy will deliver attractive returns over time, with a development program in new indications and earlier lines of therapy, Dickinson added. Trodelvy is the centerpiece of Gilead’s $21 billion acquisition of Immunomedics in 2020. In the first quarter, the drug delivered a 39% sales increase to $309 million. While concerns that Gilead overpaid were raised from the beginning, Dickinson now said Gilead is exploring opportunities that were not included in the initial deal model. Details of the failed EVOKE-01 trial will be shared at the upcoming American Society of Clinical Oncology annual meeting. Despite the primary endpoint flop, the full dataset “motivates us to go forward in lung cancer, including discussions with regulators,” Chief Medical Officer Merdad Parsey said during the call. The company will share more once the results are provided, he said. Trodelvy has a busy year ahead. Besides the EVOKE-01 trial, Gilead has seven ongoing phase 3 trials across breast, bladder and lung cancers, and plans to start another phase 3 in endometrial cancer in 2024. Readouts and updates are expected later this year from the multi-cohort phase 3 EVOKE-02 trial, including data from first-line NSCLC patients that got a combination of Trodelvy, Merck’s Keytruda and chemotherapy. The confirmatory TROPiCS-04 trial for Trodelvy in bladder cancer could read out overall survival results this year, Parsey said. The phase 3 ASCENT-03 study in first-line PD-L1-negative triple-negative breast cancer will also have an update. Gilead is shoring up Trodelvy’s clinical data as AstraZeneca and Daiichi Sankyo are closing in on an FDA approval for their rival TROP2 ADC, datopotamab deruxtecan (Dato-DXd) in previously treated nonsquamous NSCLC. The FDA has set Dec. 20 as the target decision date. The flurry of Trodelvy developments accentuates what Gilead CEO Dan O’Day called “a time of focused execution” at the big biotech. Cell therapies, the other pillar of Gilead’s growing oncology portfolio, have recently reached a bottleneck. Sales from the CD19 CAR-Ts, Yescarta and Tecartus, have been relatively flat sequentially for the last three quarters. The two therapies together brought in $480 million in sales in the first quarter, versus $486 million in the third quarter of 2023 and $466 million in the last three months of the year. The FDA has installed new boxed warnings on the two CAR-T therapies’ labels reflecting a class-wide concern of secondary T-cell malignancies following the treatment of existing CAR-Ts. The lack of growth momentum was the result of an infrastructure bottleneck at designated treatment centers. To solve the problem, Gilead is working to expand the number of authorized centers and affiliated satellites, while also driving increased referrals from community doctors, chief commercial officer, Johanna Mercier, said on the call. The company earlier this year established a flagship community collaboration with Tennessee Oncology, she said. “We’ve identified many critical learnings on how we can partner effectively with community oncology practices for cell therapy, and we will continue to refine this blueprint so that we become more efficient at onboarding new centers over time,” Mercier said. Gilead expects to see the fruits of the expansion toward the end of 2024, she added. In Gilead’s bread-and-butter HIV franchise, Biktarvy remains king in the market with sales reaching $2.9 billion and market share at 49% in the first quarter. But the company is racing against GSK on developing long-acting regimens. Gilead plans to advance a long-delayed phase 3 trial later this year for long-acting Sunlenca (lenacapavir) with Merck’s islatravir as a once-weekly regimen, plus a phase 2 trial for a combination of a capsid inhibitor and a novel integrase inhibitor. Meanwhile, Gilead is looking to potentially launch lenacapavir as early as late 2025 as the first twice-yearly PrEP option for HIV. Outside of antiviral and oncology, Gilead just wrapped up the $4.3 billion acquisition of CymaBay Therapeutics and gained the liver disease candidate seladelpar, which has filings before the FDA and the European Medicines Agency as a treatment for primary biliary cholangitis. If the FDA clears the drug in August, Gilead expects to leverage its liver disease expertise gathered from the hepatitis C virus franchise. The company’s sales force currently covers nearly 80% of the U.S. prescriber base in PBC, Mercier said.