Merdad Parsey
Chief Medical Officer at Gilead Sciences
Thanks, Johanna, and good afternoon everyone. Building on what both Johanna and Dan have said, the Gilead team rounded out a very strong 2021 with further progress across our portfolio. In 2021 alone, we began enrolling patients in 13 oncology, 13 virology, and four inflammation trials, and we have recently shared the initial details of our ambitious development programs we are targeting for 2022. As we look forward, we're confident that we have the foundation to continue to build a robust, diverse portfolio across our three focus therapeutic areas.
First, on Slide 16, Veklury continues to play a vital role in the fight against COVID-19. Veklury was the first approved treatment for patients hospitalized with COVID-19. And we have received expanded indication labels in the U.S. and EU. In December, the European Commission approved a variation to the Conditional Marketing Authorization for Veklury for the treatment of COVID-19 in adults not on supplemental oxygen. And last month, based on data from the Phase 3 PINETREE study, the FDA expanded the approval of Veklury to include non-hospitalized patients at high risk for COVID-19 disease progression. These expanded indications speak to the activity of Veklury against the coronavirus variants we've seen so far, including Omicron.
We believe there will continue to be a need for Veklury delivered intravenously, especially for higher risk patients. The potential for continued COVID-19 variants and infections highlight the need for more convenient oral formulations to expand the options for outpatients. As such, we've just initiated a Phase 1 trial of GS-5245, a novel oral COVID-19 nucleoside, that once metabolized, works in the same way as remdesivir. Pending data, the evolving pandemic landscape, and discussions with regulatory agencies, we're hoping to initiate a registrational trial before the end of the year.
Moving to HIV on Slide 17, we shared an overview of some of our long-acting development activities a few weeks ago, to highlight the diversity of our portfolio and how it targets the entire HIV life cycle. We continue to believe that our investigational agent lenacapavir is a unique and foundational asset, given its potential for extended dosing, in addition to the compelling efficacy and safety profile highlighted in the CAPELLA and CALIBRATE studies.
Next, on Slide 18, you can see our current clinical efforts with long-acting HIV therapeutics. As previously announced, the Phase 2 study evaluating the oral combination of lenacapavir with Merck's islatravir is on partial clinical hold, and Merck remains in discussions with the FDA on the next steps for islatravir. In the meantime, we at Gilead continue to develop a number of other potential partner agents for lenacapavir in HIV treatment and look forward to sharing some more detail on these programs at our Virology Deep Dive later this month. We remain confident and excited about lenacapavir's future potential to deliver options for people living with HIV or those who could benefit from PrEP.
I want to be very clear that the recent clinical hold for the lenacapavir trials, which the FDA initiated in December, is not associated with the lenacapavir molecule itself. Rather, the hold reflects concerned about the compatibility of certain vials with the lenacapavir solution. We continue to work with the FDA to remediate the concern and to agree on a path to resume these trials. We are hopeful this can be achieved quickly. As such, we continue to expect an FDA decision for lenacapavir in heavily treatment experienced individuals in the first half of 2022. If successful, lenacapavir will become the first available six month, long-acting subcutaneous injection for the treatment of HIV.
Next, moving to Trodelvy on Slide 18, I'm pleased to confirm that we now expect to share both top line progression free survival data, as well as the first planned interim analysis of overall survival from TROPiCS-02 in March. There's been a convergence of events for PFS and OS such that we'll be able to conduct and report a single analysis of these outcomes rather than have two analyses separated by a short interval. Gilead remains blinded to the data, and we're excited to be able to share this more complete view later this quarter. We are targeting an sBLA filing in the second half of 2022, depending, of course, on the readout.
If the data are positive, we believe that Trodelvy could represent a very important treatment option for HR+/HER2- patients who are hormone refractory and have very limited options. Reflecting our confidence in Trodelvy overall, we are expanding the number of clinical programs in 2022 to evaluate effectiveness in breast, lung and bladder cancers, with plans to initiate study start-up activities for at least seven Phase 3 trials. Three of these are expected to enroll their first patients in 2022, including two in front-line metastatic TNBC and another in front-line non-small cell lung cancer study, that'll be led by Merck.
Going forward, we will separately disclose trial start up activities versus FPI milestones. Additionally, in the first half of this year, we plan to add a combination of Trodelvy with other Gilead portfolio assets as a study or an additional cohort in an existing study. We look forward to sharing more details at our upcoming Oncology Deep Dive in April. This is another example of the versatility and tremendous potential that Trodelvy, along with the growing oncology portfolio, can generate.
Next slide, onto magrolimab. Early last week, the FDA placed a partial clinical hold pausing enrollment and screening in trials and cohorts in the U.S. evaluating magrolimab in combination with azacitidine following review of a preliminary dataset, suggesting an apparent imbalance in investigator-reported SUSARs or unexpected -- sorry, suspected unexpected serious adverse reactions, between treatment groups in our ongoing Phase 3 trial in high risk MDS. A subsequent partial clinical hold has been placed on the Phase 2 multiple myeloma study and the fully enrolled Phase 2 DLBCL study. Importantly, patients currently enrolled in our magrolimab studies can continue treatment and our compassionate use programs remain open.
We're working with FDA to take a comprehensive look at the safety data, and we'll share the outcome as quickly as we can. In the meantime, we remain committed to the magrolimab development program and believe that it has the potential to address an important unmet medical need in these seriously ill patients. As you know, the patients in our ENHANCE Phase 3 trial have a very high unmet need, with a median overall survival of only one to three years on the current standard of care.
Separate from and prior to the partial clinical hold, our Phase 1b single-arm study in higher risk MDS no longer has a viable path to submission based on regulatory feedback. As such, we will remain focused on our Phase 3 ENHANCE study and look forward to sharing the 1b data at an upcoming scientific meeting.
Next, moving to cell therapy on Slide 21. On behalf of Christi and the Kite team, I'll share a brief update on the impressive data Kite presented at ASH last December. First, as you may recall, in 2020 we shared that Yescarta had a four year overall survival rate of 44% in third-line LBCL patients. At ASH in December, we presented five year data from ZUMA-1 in third-line LBCL patients showing Yescarta demonstrated a remarkable and durable 43% overall survival rate, stable since our four year update. Additionally, 92% of the patients who remained alive at five years have not needed any additional cancer treatment since their one-time infusion of Yescarta. It's truly inspiring to see this type of durability for CAR T cell therapies.
As announced yesterday, the FDA approved a label update for Yescarta to include use of prophylactic corticosteroids across all approved indications. Adding prophylactic steroid use can improve the management of certain side effects without compromising the activity of Yescarta. For example, the FDA label now shows no grade 3 or greater cytokine release syndrome events occurred using the Cohort 6 protocol, as compared to 13% in the original label. This label update compliments data published in 2021 showing 68% of patients had no CRS or neurological events within 72 hours of Yescarta infusion.
As we look to earlier lines of treatment, the landmark ZUMA-7 trial evaluating Yescarta in second-line relapsed/refractory LBCL demonstrated a greater than four-fold increase in median event free survival, or EFS, compared to standard of care through two years of follow-up. As you can see on the slide, the EFS curve for Yescarta is compelling. The sBLA was filed last quarter and we expect an FDA decision by April of this year. In terms of the first-line LBCL data, Yescarta demonstrated 89% overall response rate in high-risk patients, and 78% complete response with a median follow-up of 15.9 months. Given these encouraging data, the Kite team is in discussions with regulatory authorities on a potential path forward in front line LBCL.
And finally, on Slide 22, we highlight the key 2022 catalysts across the portfolio, many of which I've just mentioned. I'd also like to take a moment to highlight the three Arcus milestones in the second half of this year. Last quarter, Gilead opted in to the three Arcus programs, which added four assets to our portfolio: domvanalimab; an Fc silent TIGIT antibody; AB308, an Fc active TIGIT antibody; etrumadenant, an adenosine receptor antagonist; and quemliclustat, a small molecule CD73 inhibitor.
Together with Arcus, we expect to share ARC-7 Phase 2 PFS data in the second half of 2022, which will include data for the zimberelimab monotherapy, zim and dom doublet, as well as the zim, dom and etruma triplet arm. We look forward to sharing data when available and are very excited to collaborate more closely with Arcus to accelerate future development plans.
On Slide 23, you can see that Gilead's portfolio now encompasses 55 clinical stage programs, nearly doubling since 2019. Given the exciting potential of our portfolio across virology, oncology, and early stage inflammation assets, this is just the beginning. Our teams are committed to advancing the most promising programs that will help transform patient outcomes, and we look forward to sharing our progress with you over the coming quarters and years.
With that, I'll hand it over to Andy.
