It might seem like luck for a company to trip over a multi-billion dollar COVID treatment already lurking in its pipeline – but perhaps not so much when that company, Gilead, has been at the leading edge of antiviral R&D for decades.

By Joshua Slatko • [email protected]


Gilead SciencesGilead Sciences

333 Lakeside Drive

Foster City, CA 94404

650-574-3000 •

Financial Performance
  2021 2020 1H 2022 1H 2021
Revenue $27,305 $24,689 $12,850 $12,640
Net income $6,201 $89 $1,147 $3,239
Diluted EPS $4.93 $0.10 $0.92 $2.58
R&D expense $5,363 $5,039 $2,280 $2,142
All figures are in millions of dollars, except EPS.

Best-selling products

All sales are in millions of dollars.

2021 sales

  • Biktarvy $8,624 
  • Veklury $5,565 
  • Genvoya $2,879 
  • Descovy $1,700 
  • Odefsey $1,568 
  • Epclusa $1,462 
  • Vemlidy $814
  • Yescarta $695
  • Ambisome $540 
  • Symtuza $531

1H 2022 sales

  • Biktarvy $4,707 
  • Veklury $1,980 
  • Genvoya $1,164 
  • Descovy $834 
  • Epclusa $706 
  • Odefsey $703 
  • Yescarta $506 
  • Vemlidy $394 
  • Trodelvy $305 
  • Ambisome $275 
  • Symtuza $258

Outcomes Creativity Index Score: 10

  • Manny Awards — N/A
  • Cannes Lions — N/A
  • Clio Health — 5
  • Creative Floor Awards — N/A
  • London International Awards – N/A
  • MM+M Awards — 5
  • One Show — N/A


Daniel O'Day, Gilead Sciences

Chairman and CEO Daniel O’Day

The history of scientific serendipity is long – think the apple that beaned Isaac Newton or Alexander Fleming’s contaminated culture plate – and Gilead’s Veklury has surely added an entry to the list. Originally developed as a treatment for hepatitis C and later investigated in Ebola and Marburg virus, Veklury was just another failed antiviral until researchers at the company realized it might be effective against COVID-19. Two years and more than $10 billion in sales later, Veklury is now one of the world’s leading treatments for COVID. Serendipity, perhaps; but given Gilead’s long history in HIV, HBV, HCV, and plenty of other V’s, not really at all surprising. 

“Gilead’s long-term research into emerging viruses and decades of investment in antiviral therapies allowed us to move quickly from the very start of the pandemic,” said Daniel O’Day, Gilead’s chairman and CEO, in May 2021. “Because of the work we had previously done on Veklury, we had seen its potential as a treatment for COVID-19. The entire company rallied to contribute to the work on Veklury. We expanded our manufacturing capability, ran multiple clinical studies, and collaborated with many partners to bring the therapy to patients. Veklury became the first FDA-approved therapy for COVID-19 and by the end of 2020, it was being used to treat one in two hospitalized patients for COVID-19 in the United States.”

Gilead’s top-line revenue was $27.31 billion in 2021, an improvement of 10.6 percent. Net income for the year came in at $6.2 billion, and earnings per share were $4.93. The company’s bottom line in 2020 was impacted by a number of one-time items, leading to that year’s GAAP net income of just $89 million, but company leaders put non-GAAP EPS at $7.09 for 2020 and $7.28 for 2021, an improvement of 2.7 percent. In the first half of 2022 Gilead’s top line edged up by 1.7 percent to $12.85 billion, while net income declined from $3.24 billion to $1.15 billion and EPS fell from $2.58 to $0.92. According to company leadership, this was due to a $2.7 billion in-process research and development impairment related to assets acquired by Gilead from Immunomedics in 2020, as well as in-process R&D expenses from an upfront payment of $300 million related to the Dragonfly Therapeutics collaboration and higher net unrealized losses from the company’s strategic equity investments.

Partnerships and acquisitions

In January, Gilead and Merck entered into two clinical trial collaboration and supply agreements to evaluate the combination of Trodelvy and Merck’s anti-PD-1 therapy Key-truda in first-line metastatic non-small cell lung cancer. As part of the collaboration, Merck will sponsor a global Phase III clinical trial of Trodelvy in combination with Keytruda as a first-line treatment for patients with metastatic NSCLC. Additionally, the companies established an agreement whereby Gilead will sponsor a Phase II signal-seeking study evaluating combinations that include Keytruda in first-line NSCLC. These agreements followed a collaboration, established in October 2021, to investigate Trodelvy in combination with Keytruda as first-line treatment for people with locally advanced or metastatic triple-negative breast cancer.

In May, Gilead and Dragonfly Therapeutics announced a collaboration designed to advance a number of Dragonfly’s novel natural killer cell engager-based immunotherapies for oncology and inflammation indications. According to company executives, NK cell engagers represent a novel mechanism with the potential to address a broad range of cancers, including potential for activity in checkpoint resistant and refractory tumors, as well as other disease areas such as inflammation. Under the agreement, Gilead will receive an exclusive, worldwide license from Dragonfly for the 5T4-targeting investigational immunotherapy program DF7001. The agreement also grants Gilead options, after the completion of certain preclinical activities, to license exclusive, worldwide rights to develop and commercialize additional NK cell engager programs using the Dragonfly Tri-specific NK Engager (TriNKET) platform. TriNKETs are activators of the innate and adaptive immune systems, recruiting NK and cytotoxic T cells into the tumor microenvironment.

DF7001 is a TriNKET designed to activate and direct NK and cytotoxic T cell killing against cancer cells. The target of DF7001 is 5T4, a protein expressed on cancer cells and stromal cells that support tumor growth associated with poor prognosis in several cancers, including non-small cell lung cancer, pancreatic cancer, breast cancer, and head and neck squamous cell carcinomas. DF7001, company leaders say, has the potential to trigger the killing of 5T4+ expressing cells, including tumor cells, cancer-associated fibroblasts, and cancer stem cells. The program is on track for filing an Investigational New Drug application in the first half of 2023.

In August, Gilead agreed to acquire MiroBio, a privately held U.K.-based biotechnology company focused on restoring immune balance with agonists targeting immune inhibitory receptors, for about $405 million in cash. The acquisition, company leaders say, will provide Gilead with MiroBio’s proprietary discovery platform and entire portfolio of immune inhibitory receptor agonists. MiroBio’s lead investigational antibody, MB272, is a selective agonist of immune inhibitory receptor B- and T-Lymphocyte Attenuator (BTLA) and has entered Phase I clinical trials. MB272 targets T, B and dendritic cells to inhibit or blunt activation and suppress an inflammatory immune response.

According to company executives, MiroBio’s I-ReSToRE platform (REceptor Selection and Targeting to Reinstate immune Equilibrium) has the potential to be used to develop best-in-class agonist antibodies targeting immune inhibitory receptors, a novel approach to the treatment of inflammatory diseases. The I-ReSToRE platform supports identification and development of therapeutics that utilize inhibitory signaling networks with the goal of restoring immune homeostasis for patients. Gilead leaders anticipate advancing additional agonists derived from MiroBio’s I-ReSToRE platform, including a PD-1 agonist, MB151, and other undisclosed early-stage programs, over the next several years.

Also in August, Gilead announced a new health equity collaboration with the Satcher Health Leadership Institute (SHLI) at Morehouse School of Medicine and the Center for Minority Health and Health Disparities Research and Education (CMHDRE) at Xavier University of Louisiana’s College of Pharmacy. The collaboration is focused on addressing the inequities in HIV care for Black communities in the Southern United States. According to company leaders, Gilead has a broad and long-standing commitment to advancing global health equity, which it regards as critical to helping to end the HIV epidemic and improving health outcomes for all. The company’s health equity strategy focuses on collaborating with organizations that reach underrepresented and disproportionately impacted communities.

The partnership between SHLI and CMHDRE, with support from Gilead, is intended to close gaps in care by increasing understanding of the impact of COVID-19 on the healthcare delivery system in the Black community; realigning HIV services to reflect the impact of the COVID-19 pandemic; providing training focused on culturally appropriate HIV care, inclusive of stigma-reducing strategies; and increasing access to, and utilization of, culturally appropriate care for Black people impacted by the HIV epidemic.

Product performance


Biktarvy remained the world’s best-selling HIV treatment in 2021 with sales of $8.62 billion.

The HIV product Biktarvy enjoyed a sales jump of 18.8 percent to $8.62 billion in 2021, solidifying its place as the best-selling HIV treatment worldwide. According to company leaders, this was due to higher demand and higher net average selling price driven by favorable changes in estimates of government rebates and discounts in the United States. In the first half of 2022, sales of Biktarvy rose another 23.3 percent to $4.71 billion. 

In July, Gilead announced study results reinforcing Biktarvy as a highly efficacious treatment option for a broad range of people with HIV, including individuals with HIV/hepatitis B (HBV) coinfection. Interim data from the ALLIANCE trial evaluating Biktarvy in adults with HIV/HBV coinfection who were initiating therapy showed potential suppression of HBV and HIV suppression comparable to an alternative HIV regimen. Additionally, 5-year data from two Phase III trials further demonstrated Biktarvy’s sustained efficacy, safety profile and high barrier to resistance in adults with HIV initiating therapy.

Data from the ALLIANCE trial, which is an ongoing Phase III trial evaluating Biktarvy versus dolutegravir 50 mg (DTG) + emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg, F/TDF, DTG+F/TDF, demonstrated the efficacy of both antiretroviral regimens, in adults with HIV/HBV co-infection initiating treatment. The Week 48 results showed Biktarvy demonstrated superior HBV DNA suppression. Importantly, participants who initiated treatment with Biktarvy versus DTG+F/TDF demonstrated superior HBV DNA suppression (<29 IU/mL) (63 percent versus 43 percent) and hepatitis B e-antigen (HBeAg) seroconversion (23 percent versus 11 percent). The Week 48 results also showed that participants who initiated treatment with Biktarvy or DTG+F/TDF both had similarly high rates of HIV suppression (HIV-1 RNA <50 copies/ml). Participants who initiated treatment with Biktarvy or DTG+F/TDF both had high rates of HIV suppression at Week 48 (95 percent versus 91 percent) with mean CD4 cell count increases of 200 and 175 cells/µl from baseline, respectively.

Five-year cumulative data from two other trials also demonstrated Biktarvy’s sustained efficacy and durable viral suppression as first-line therapy in people with HIV. No cases of treatment failure due to emergent resistance were detected in an analysis of five years of data from both studies, which further demonstrates the efficacy and tolerability profile of Biktarvy for the treatment of HIV in adults with no prior antiretroviral therapy history. Additionally, the results from the pooled analysis of Study 1489 and Study 1490 showed that 99 percent of participants who initiated treatment with Biktarvy and remained in the study for all 240 weeks achieved and maintained an undetectable viral load (HIV-1 RNA <50 copies/mL) through five years of follow-up. In addition to high rates of virologic suppression, participants achieved a median increase in CD4 count of 317 cells/µl from baseline at Week 240.


Sales of Gilead’s Veklury – the very first COVID-19 treatment to be approved by the FDA – nearly doubled in 2021, from $2.81 billion to $5.57 billion.

Sales of Gilead’s COVID-19 treatment Veklury nearly doubled in 2021, from $2.81 billion to $5.57 billion. Veklury launched in the third quarter of 2020, so 2021 was its first full year on the market; in addition to that, company leaders credit the growth to higher hospital demand worldwide. In the first half of 2022 Veklury sales declined 13.3 percent to $1.98 billion. 

In January, FDA granted expedited approval of a supplemental new drug application for Veklury for the treatment of non-hospitalized adult and adolescent patients who are at high risk of progression to severe COVID-19, including hospitalization or death. This approval expanded the role of Veklury, which is the antiviral standard of care for the treatment of patients hospitalized with COVID-19. The expanded indication allows for Veklury to be administered in qualified outpatient settings that can administer daily intravenous infusions over three consecutive days. FDA also expanded the pediatric Emergency Use Authorization of Veklury to include non-hospitalized pediatric patients younger than 12 years of age who are at high risk of disease progression.

The FDA sNDA approval and pediatric EUA expansion were based on results from the PINETREE Phase III randomized, double-blind, placebo-controlled trial. The trial evaluated the efficacy and safety of a three-day course of Veklury for intravenous use for the treatment of COVID-19 in non-hospitalized patients at high risk for disease progression. An analysis of 562 participants randomly assigned in a 1:1 ratio to receive Veklury or placebo, demonstrated that treatment with Veklury resulted in a statistically significant 87 percent reduction in risk for the composite primary endpoint of COVID-19 related hospitalization or all-cause death by Day 28 compared with placebo. In the study, no deaths were observed in either arm by Day 28.

In February, Gilead released data demonstrating the in vitro activity of Veklury against 10 SARS-CoV-2 variants, including Omicron. Results of Gilead studies are consistent with other in vitro studies independently conducted by researchers from institutions in other countries, including Belgium, Czech Republic, Germany, Poland, and the United States, which confirmed Veklury’s antiviral activity against multiple previously identified variants of SARS-CoV-2, including Alpha, Beta, Gamma, Delta and Omicron.

In April, FDA approved a supplemental new drug application for Veklury for the treatment of pediatric patients who are older than 28 days, weighing at least 3 kg, and are either hospitalized with COVID-19 or have mild-to-moderate COVID-19 and are considered high risk for progression to severe COVID-19, including hospitalization or death. This approval was supported by results from the CARAVAN Phase II/III single arm, open-label study, which demonstrated that Veklury was generally well-tolerated among pediatric patients hospitalized with COVID-19 with a high proportion of participants showing clinical improvement and recovery, as well as data from trials in adults. Overall, 75 percent and 85 percent showed clinical improvement (≥2 point increase on the ordinal scale) at Day 10 and last assessment, respectively, while 60 percent and 83 percent were discharged by Day 10 and Day 30, respectively.

That same month, Gilead announced findings from two studies, which provide further insights on the use of Veklury for the treatment of hospitalized and non-hospitalized patients with COVID-19. The first study was a retrospective observational analysis of the real-world treatment data from the Premier Healthcare Database consisting of 853,219 patients hospitalized with COVID-19 across the United States. This analysis found that more than 50 percent of hospitalized COVID-19 patients received Veklury, predominantly in combination with other therapies. A separate study, which is a new post-hoc analysis of data from the Phase III PINETREE study, demonstrated that use of Veklury within five days of symptom onset or between 5 to 7 days of symptom onset reduced hospitalizations in patients at high risk for severe COVID-19.

The observational analysis of real-world data also found that as the pandemic progressed, initiation of Veklury within two days of hospitalization increased from 41 percent to 91 percent between May 2020 and December 2021. During this period, as new variants arose and disease severity fluctuated, median hospital length of stay decreased from seven to six days with the greatest benefit in invasive mechanical ventilation/ ECMO patients (15 to 11 days). While ICU use decreased from 34 percent to 27 percent, with the greatest benefit in high-flow oxygen/non-invasive ventilation (66 percent to 52 percent), overall ICU LOS remained the same. Overall mortality rates remained stable at 16 percent, with the greatest decline over time in patients on low-flow supplemental oxygen (15 percent to 12 percent).

The new post-hoc analysis from a Phase III double-blind, placebo-controlled trial (PINETREE) assessed the variability of treatment effect with Veklury by time of symptom onset and number of baseline risk factors. The study concluded that Veklury reduced hospitalizations in patients at high risk for severe COVID-19 disease when initiated anytime within a 7-day window from symptom onset. As expected with antiviral therapy, the benefit was modestly greater the sooner Veklury was administered. Patients treated with Veklury within five days of symptom onset had a 90 percent reduced risk for hospitalization. Additionally, patients who received Veklury after five days of symptom onset experienced an 81 percent reduction in risk of hospitalization. This new analysis builds on the previously presented primary endpoint analysis, in which Veklury demonstrated a statistically significant 87 percent reduction in risk for the composite primary endpoint of COVID-19 related hospitalization or all-cause death by Day 28 compared with placebo; no deaths occurred in either arm of the study through the primary endpoint.

Gilead’s second-leading HIV drug Genvoya generated sales of $2.88 billion for the company in 2021, a decline of 13.8 percent. According to company executives, this was due to patients switching to Biktarvy. In the first half of 2022 Genvoya sales declined another 15.6 percent to $1.16 billion. 

Sales of the HIV drug Descovy also declined in 2021, falling 8.7 percent to $1.7 billion. This was for much the same reason as Genvoya; Biktarvy is a formulation of Descovy plus bictegravir. In the first half of 2022, Descovy sales rose 5 percent to $834 million. 

Odefsey, another Descovy relative, generated $1.57 billion in sales for Gilead in 2021, a decline of 6.2 percent. Sales of Odefsey dropped another 6.1 percent in the first half of 2022, to $703 million.

Gilead’s hepatitis C product Epclusa brought in sales of $1.46 billion in 2021, down 8.6 percent compared with the previous year. According to company leaders, this was primarily due to lower demand driven by fewer patient starts worldwide due to the impact of the COVID-19 pandemic. In the first half of 2022, sales of Epclusa declined another 14.2 percent to $706 million.

Sales of the hepatitis B treatment Vemlidy enjoyed a bounce of 23.9 percent in 2021, rising to $814 million. Gilead leaders credited this to higher demand in all geographies. In the first half of 2022, sales of Vemlidy edged up another 3.4 percent to $394 million.


Sales of the CAR T therapy Yescarta rose by nearly half in the first half of 2022 as the product earned new approvals from the FDA and the European Commission in large B-cell and follicular lymphoma.

The CAR T oncologic therapy Yescarta generated sales of $695 million for Gilead in 2021, an improvement of 23.4 percent. Company leaders said this was driven by continued higher demand for Yescarta worldwide for large B-cell lymphoma and volume growth related to approval of Yescarta for follicular lymphoma in the United States in 2021. Firs-half 2022 sales of Yescarta rose another 49.7 percent to $506 million.

In January, the FDA approved an update to the prescribing information for Yescarta to include use of prophylactic corticosteroids across all approved indications. With this update Yescarta became the first and only CAR T-cell therapy with information in the label to help physicians manage, and potentially prevent, treatment side effects.

The label update was based on the results of a new safety management cohort (Cohort 6) of the pivotal ZUMA-1 study, which was designed to assess the impact of prophylactic use of corticosteroids and earlier treatment with corticosteroids and/or tocilizumab and prophylactic levetiracetam on the incidence and severity of cytokine release syndrome and neurologic events. In the cohort, no Grade ≥3 CRS events occurred in patients in Cohort 6 compared to 13 percent in the pivotal Cohorts 1/2. Grade ≥3 neurologic events occurred in 13 percent of patients at the time of data cut-off, and one patient experienced a late onset Grade 5 event following the data cut-off (13 percent of patients in Cohort 6 compared to 31 percent in the pivotal Cohorts 1/2). Cohort 6 shows CRS median time to onset of five days with a range from 1-15 days, and neurotoxicity median time to onset of six days with a range from 1-274 days in patients that experienced these complications. 

During April, the FDA approved Yescarta for adult patients with large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy. The marketing approval was based on results from the ZUMA-7 study, in which Yescarta demonstrated a clinically meaningful and statistically significant improvement in event-free survival over the current standard of care that has been in place for decades. EFS was determined by blinded central review and defined as the time from randomization to the earliest date of disease progression, commencement of new lymphoma therapy, or death from any cause. Additionally, 2.5 times more patients receiving Yescarta (40.5 percent) were alive at two years without disease progression or need for additional cancer treatment, after their one-time infusion of Yescarta versus SOC (16.3 percent), and the median EFS was four-fold greater (8.3 months versus 2.0 months) with Yescarta versus SOC.

In June, the European Commission approved Yescarta for the treatment of adult patients with relapsed or refractory follicular lymphoma after three or more lines of systemic therapy. The approval was supported by data from the pivotal, single-arm Phase II ZUMA-5 international study in patients with relapsed or refractory FL who had received at least two prior lines of systemic therapy, including the combination of an anti-CD20 monoclonal antibody and an alkylating agent. Among patients who had received three or more lines of prior therapy, the overall response rate was 91 percent, and the complete response rate was 77 percent at the 24-month analysis. The median duration of response was 38.6 months, and the proportion of responders still in response at Month 24 was 56 percent.

Also during June, the Gilead company Kite announced findings from a safety and efficacy retrospective analysis by race and ethnicity from the ongoing post-authorization study of Yescarta in adult patients with relapsed or refractory large B-cell lymphoma. In the largest real-world analysis of its kind evaluating data from the CIBMTR (Center for International Blood and Marrow Transplant Research), overall outcomes including overall survival (OS) and progression-free survival (PFS) rates were consistent with Yescarta in the real-world setting, regardless of race and ethnicity.

Multivariable analyses found no statistical differences in OS and PFS across races. Efficacy outcomes across patients who were Hispanic or Latino and not Hispanic or Latino were also consistent. Among Black or African American patients, ORR and CR were lower compared to White patients. Black or African American patients, compared to White patients, were more likely to have moderate to severe pulmonary impairment (41 percent versus 28 percent) and tended to have a longer time from diagnosis to infusion of Yescarta (≥12 months: 71 percent versus 59 percent). DOR rates among Asian patients were more favorable compared to both White patients and Black or African American patients. No differences in cytokine release syndrome (CRS; any grade) and Grade ≥3 CRS by race and ethnicity were observed. Asian patients and Hispanic or Latino patients experienced a lower risk of Grade ≥3 ICANS (ASTCT consensus grade).

Acquired in the Immunomedics transaction in the fourth quarter of 2020, the oncologic Trodelvy enjoyed sales of $380 million in its first full year under the Gilead banner, helped along by approval for metastatic triple negative breast cancer in the United States and Europe and accelerated approval for metastatic urothelial carcinoma in the United States. In the first half of 2022, sales of Trodelvy nearly doubled, from $161 million to $305 million. 

In June, Gilead presented final data from the Phase III ASCENT study of Trodelvy in patients with relapsed or refractory metastatic triple-negative breast cancer (TNBC) who received two or more prior systemic therapies, at least one of them for metastatic disease. In a follow-up analysis from the final database lock, Trodelvy improved median progression-free survival versus physicians’ choice of chemotherapy (4.8 versus 1.7 months;) and extended median OS by almost five months (11.8 versus 6.9 months) in the intent-to-treat population. The two-year OS rate was 20.5 percent in the Trodelvy arm, compared with 5.5 percent with physicians’ choice of chemotherapy. Trodelvy also showed clinically meaningful improvements in health-related quality of life compared to chemotherapy.

Also during June, Gilead announced positive results from the primary analysis of the Phase III TROPiCS-02 study of Trodelvy versus physicians’ choice of chemotherapy (TPC) in heavily pre-treated HR+/HER2- metastatic breast cancer patients who received prior endocrine therapy, CDK4/6 inhibitors and two to four lines of chemotherapy. The study met its primary endpoint of PFS with a statistically significant and clinically meaningful 34 percent reduction in the risk of disease progression or death (median PFS 5.5 versus 4 months). The first interim analysis of the key secondary endpoint of OS demonstrated a trend in improvement.

The study demonstrated that at the one-year mark, three times as many patients were progression-free when treated with Trodelvy compared to those who received TPC (21 percent versus 7 percent). Improvements in PFS with Trodelvy were also consistent across key patient subgroups, including patients who had previously received three or more chemotherapy regimens for metastatic disease, patients with visceral metastasis, and the elderly (≥65 years of age).

In September, Gilead announced new data from a post hoc subgroup analysis from the Phase III TROPiCS-02 study evaluating Trodelvy versus comparator chemotherapies (physicians’ choice of chemotherapy, TPC) in patients with HR+/HER2- metastatic breast cancer who progressed on endocrine-based therapies and at least two chemotherapies. The analysis examined PFS in the intention-to-treat population by HER2-immunohistochemistry (IHC) status, and the results demonstrated that Trodelvy improved median PFS vs. TPC in both HER2-low (IHC1+ and IHC2+/ISH-negative) and IHC0 groups.

In the pipeline

In April, the FDA lifted the partial clinical hold placed on studies evaluating Gilead’s investigational agent magrolimab in combination with azacitidine. The FDA removed the partial clinical hold after a review of the comprehensive safety data from each trial. U.S. enrollment can resume for the studies investigating magrolimab in combination with azacitidine in myelodysplastic syndrome and acute myeloid leukemia. Gilead, in coordination with regulatory authorities, is planning to re-open enrollment in the magrolimab studies that were placed on a voluntary hold outside of the United States. The company is also working with the FDA regarding the remaining partial clinical hold affecting studies evaluating magrolimab in diffuse large B-cell lymphoma and multiple myeloma. The ongoing clinical studies evaluating magrolimab in solid tumors were not subject to the clinical hold.

In May, the FDA lifted the clinical hold placed on Gilead’s Investigational New Drug Application to evaluate injectable lenacapavir (Sunleca) for HIV treatment and HIV pre-exposure prophylaxis. The regulatory agency had placed a clinical hold on the use of injectable lenacapavir in borosilicate vials due to a vial compatibility issue. The FDA removed the clinical hold following the agency’s review of Gilead’s comprehensive plan and corresponding data on the storage and compatibility of lenacapavir injection with an alternative vial made from aluminosilicate glass.

In June, Kite announced longer-term follow-up results from two pivotal studies of the CAR T-cell therapy Tecartus in patients with relapsed/refractory (R/R) mantle cell lymphoma and in adult patients (≥18 years old) with R/R B-cell acute lymphoblastic leukemia. At nearly three years of follow-up (median 35.6 months) in the ZUMA-2 trial in patients with relapsed/refractory mantle cell lymphoma, the overall response rate was 91 percent, with 68 percent of treated patients achieving a complete response. The median duration of response was 28.2 months, with 37 percent of treated patients in ongoing response at data cut-off. Median overall survival among treated patients was 46.6 months. Among those patients who achieved a CR, the median OS has not yet been reached (30-month OS rate was 60.3 percent). Late relapse, classified as more than 24 months post-infusion, was infrequent.

In the ZUMA-3 trial in adult patients (≥18 years old) with R/R B-cell acute lymphoblastic leukemia, longer follow-up of the pivotal analysis and outcomes of a newly-conducted larger pooled analysis of Phase I and II patients by independent review who received the pivotal dose of Tecartus were reported. Most patients in the analysis were heavily pre-treated, with a median of two prior therapies, and 47 percent had received three or more prior therapies. At a median follow-up of 29.7 months for pooled Phase I and II patients, 73.1 percent of treated patients achieved a CR or CR with incomplete hematological recovery. Median OS was 25.4 months for both Phase II treated patients and pooled Phase I and II treated patients. At data cutoff, median OS had not yet been reached in Phase II patients who achieved a CR. Similar outcomes among Phase II treated patients and the pooled analysis of Phase I and II patients were observed.

Also in June, Gilead announced Week 48 results from the Phase III clinical trial evaluating the first-in-class entry inhibitor Hepcludex for the treatment of chronic hepatitis delta virus infection. At Week 48, study participants treated with Hepcludex monotherapy at 2 mg or 10 mg once daily achieved a significantly greater combined virological and biochemical response (45 percent and 48 percent, respectively) when compared to participants who had not received antiviral treatment at this stage of the study (2 percent). Combined response was defined as undetectable HDV RNA or a decrease by 2 log10 IU/mL from baseline and ALT normalization. Similarly, when the Week 48 data is considered alongside the integrated Week 24 analyses of the ongoing Phase II studies (MYR202 and MYR203) and the interim Week 24 Phase III MYR301 data, combined response rates of Hepcludex increased from Week 24 to Week 48, highlighting an improved response of Hepcludex with prolonged treatment.

In August, the European Commission granted Marketing Authorization for Sunlenca injection and tablets for the treatment of HIV infection, in combination with other antiretroviral(s), in adults with multi-drug resistant HIV infection for whom it is otherwise not possible to construct a suppressive anti-viral regimen. Sunlenca is a first-in-class capsid inhibitor with a multi-stage mechanism of action and has no known cross resistance to other existing drug classes, offering a new, every six-month treatment option for people with HIV whose virus no longer effectively responds to their current therapy. 

The approval was supported by data from the Phase II/III CAPELLA study, which evaluated Sunlenca in combination with an optimized background regimen in people with multi-drug resistant HIV who are heavily treatment-experienced. In this patient population with significant unmet medical need, 83 percent of participants receiving Sunlenca in addition to an optimized background regimen achieved an undetectable viral load (<50 copies/mL) at Week 52. CAPELLA participants achieved a mean increase in CD4 count of 83 cells/µL. 

In September, the European Commission approved Tecartus for the treatment of adult patients 26 years of age and above with relapsed or refractory (r/r) B-cell precursor acute lymphoblastic leukemia. The approval was supported by data from the ZUMA-3 international multicenter, single-arm, open-label, registrational Phase I/II study of adult patients (≥18 years old) with relapsed or refractory ALL. This study demonstrated that 71 percent of the evaluable patients achieved complete remission or CR with incomplete hematological recovery with a median follow-up of 26.8 months. In an extended data set of all pivotal dosed patients the median OS for all patients was more than two years (25.4 months) and almost four years (47 months) for responders (patients who achieved CR or CRi). Among efficacy-evaluable patients, median duration of remission was 18.6 months.