George D. Yancopoulos
Board Co-Chair, President and Chief Scientific Officer at Regeneron Pharmaceuticals
Thanks, Len.
I'll start with EYLEA HD and the data from the PHOTON extension study in diabetic macular edema, that were recently presented at the American Academy of Ophthalmology Annual Meeting. In addition to demonstrating that the vision gains and anatomic achievements or improvements with EYLEA HD over two years could be sustained over a third year of treatment at EYLEA HD, the results of the extension study provided the first data for patients who switched from EYLEA to EYLEA HD.
For these switch patients who were dosed for 88 weeks with EYLEA every eight weeks following five initial loading doses, retinal fluid reaccumulation was substantially slower after a single EYLEA HD injection at week 96 as compared to these patients' previous rate of fluid accumulation with our EYLEA 2 milligram. In addition, after one year of EYLEA HD treatment, 83% of these switch patients had a last assigned dosing interval of at least 12 weeks.
Importantly, mean visual and anatomic achievement improvements achieved with EYLEA were sustained following the switch to longer dosing intervals with EYLEA HD. For PHOTON, patients assigned to EYLEA HD treatment groups at baseline, visual gains and anatomic improvements achieved in the first two years were all sustained in three years, but many of these patients were able to meaningfully extend their dosing interval. At the end of three years of treatment, nearly half were signed the final dosing interval of at least 20 weeks.
In summary, EYLEA HD achieved consistently longer dosing intervals as well as notably slower fluid reaccumulation as compared to EYLEA, a first for the category. When all other anti-VEGF agents were compared to EYLEA and head-to-head studies, these agents did not demonstrate slow fluid reaccumulation. The safety profile of EYLEA HD has continued to be similar to EYLEA through three years and remain generally consistent with the known safety profile of EYLEA HD in its pivotal trials. Altogether, these data support our belief that EYLEA HD has a best-in-class profile.
Now moving to DUPIXENT, which achieved several first and only clinical and regulatory milestones since our second quarter earnings call in early August. First, we are pleased to receive U.S. regulatory approval for DUPIXENT as an add-on maintenance treatment of adult patients with inadequately controlled COPD and the eosinophilic phenotype, marking the first ever biologic approved to treat this disease and represent DUPIXENT's six indications approved in the United States.
Also in COPD, as Len mentioned, we're looking forward to pivotal results in the second half of next year for Itepekimab, our interleukin-33 antibody. If approved in the United States, EU and Japan, Itepekimab could address approximately 1 million former smokers with COPD regardless of eosinophilic phenotypes. In terms of potential future indications for DUPIXENT, the Phase 3 ADEPT trial in moderate to severe bullous pemphigoid patients met the primary and all key secondary endpoints.
Five times more Dupixent patients achieved sustained disease remission at 36 weeks compared to those on placebo. DUPIXENT patients were far less likely than patients on placebo to relapse following steroid taper or need rescue therapy during the treatment period. Based on these data, DUPIXENT is the first and only biologic to achieve significant improvements in disease remission and symptoms in bullous pemphigoid, and is the first medicine to show significant steroid sparing in this disease.
We anticipate this Phase 3 ADEPT trial will support regulatory approvals around the world with the U.S. supplementary BLA submission expected by the end of the year. We also announced results of a second Phase 3 study of DUPIXENT in biologic-naive patients with chronic spontaneous urticaria, or CSU, confirming the results of a prior Phase 3 study in the same population. In this most recent study, treatment with DUPIXENT met the primary endpoint and in addition, resulted in a nearly 50% reduction in itch and urticaria activity scores from baseline, with 30% of DUPIXENT treated patients reporting a complete response or no urticaria by week 24 compared to only 18% of those on placebo.
These data, along with the data generated in the first CSU study evaluating biologically naive patients supported our supplementary BLA resubmission earlier this month, and we look forward to a potential FDA approval early next year, which would mark the first targeted therapy for CSU in a decade.
Moving to oncology, starting with Libtayo, which provides a best-in-class foundation for combinations with our other oncology assets. At the World Conference on Lung Cancer, we announced five year results from the final prespecified overall survival analysis of the Phase 3 EMPOWER-Lung 1 trial, which evaluated the entire monotherapy as a first-line treatment for adults with advanced non-small cell lung cancer with more than 50% PD-L1 expression.
The late-breaking data showed that at five years, Libtayo monotherapy nearly doubled median overall survival and reduced the risk of death by 41% compared to chemotherapy. There were also no new safety signals observed at five years among those patients. These five year outcomes data in advanced non-small cell lung cancer compare favorably across trial to other PD-1 or PD-L1 antibodies and further support Libtayo's position as the anti-PD-1 backbone for Regeneron's ongoing oncology efforts.
Moving on to one such Libtayo combination. At the recent ESMO meeting, we presented updated results of fianlimab, our LAG-3 antibody in combination with Libtayo in adults with advanced melanoma across three independent expansion cohorts of our first-in-human multi-cohort trial. With longer follow-up, these latest results showed persistent and deepening tumor responses across all cohorts. In a post hoc pooled analysis, 50% -- 57% of patients responded with 25% of these patients achieving a complete response. Median progression-free survival was 24 months. Median OS was not reaching any of the individual cohorts when the results were pooled. These fianlimab-Libtayo proof-of-concept data showed nearly double the complete response rate with more than 5 times greater median PFS than previously reported for anti-PD-1 monotherapies.
The fianlimab-Libtayo combination also showed robust clinical activity in subpopulations where there is currently no established standard of care, such as in patients previously treated with the anti-PD-1 therapy in the adjuvant or neoadjuvant setting. Of the 13 patients in this subgroup, six patients or 46% responded to therapy. Among patients receiving any adjuvant or neoadjuvant systemic therapy, 11 of 23 or 48% responded to therapy, including six complete responses.
The safety profile of the fianlimab-Libtayo combination was generally consistent with the safety profile of the libtayo monotherapy and other anti-PD-1 agents, except for higher rates of treatment-related adrenal insufficiency. Ever since the exciting early data with individual checkpoint inhibitors were presented more than a decade ago, it's been widely hypothesized that combining multiple classes of checkpoint inhibitors might meaningfully enhance antitumor activity without exacerbating safety issues, where progress to date has been broadly disappointed. We believe the results generated so far in advanced melanoma for fianlimab and Libtayo suggests it might be the first checkpoint inhibitor combination to demonstrate meaningful additive clinical benefit without significantly exacerbating safety.
Our ongoing randomized Phase 3 trial of the fianlimab-libtayo versus pembrolizumab monotherapy in previously treated, unresectable, locally advanced or metastatic melanoma is ongoing with pivotal data expected to readout next year. In addition to melanoma, we're exploring this combination in a variety of other cancer settings that have historically been responsive to anti-PD-1 therapy, including lung cancer, initial Phase 2 data for which are expected to read out by the end of this year.
Next, to our bispecifics for hematology oncology. We are pleased that the European Commission approved Ordspono or odronextamab, our CD20xCD3 bispecific for relapsed/refractory follicular lymphoma and diffuse large B-cell lymphoma, marking the first regulatory approval from our bispecific antibody platform. We continue to work on enrollment of our confirmatory studies to support resubmission of our BLA for follicular lymphoma, which we now expect to even in the first half of 2025.
Linvoseltamab, our BCMAxCD3 bispecific for myeloma. Data from the ongoing LINKER-MM1 study in patients with relapsed/refractory multiple myeloma continue to mature with responses continuing to do recall that 14 months of median follow-up among 117 patients, linvoseltamab continues to demonstrate a potentially best-in-class profile in terms of efficacy, safety dosing as well as hospitalization burden with 71% of patients respond to therapy and 50% achieving a complete response or better.
Perhaps the most differentiating about our clinical development program for both odronextamab and linvoseltamab, in earlier line settings is our plan to evaluate each agent as monotherapy as well as in limited combinations. While competing CD20 bispecifics are evaluating combinations with lenalidomide or lenalidomide plus rituximab in first-line follicular lymphoma regardless of tumor burden, our Phase 3 OLYMPIA-1 study is evaluating odronextamab monotherapy compared to R-CHOP.
Similarly, in first-line multiple myeloma, our ongoing Phase 1/2 LINKER-MM4 study is available in Linvoseltamab monotherapy. Furthermore, we are also conducting Phase 2 studies for Linvoseltamab monotherapy in precursor conditions such as smoldering myeloma and monoclonal gammopathy of undetermined significance or MGUS in an attempt to prevent progression to myeloma.
Now to our non-oncology hematology pipeline, starting with our C5 program, which is the first combination of an antibody and siRNA that targets the same protein. We expect to present updated results for one potential indication paroxysmal nocturnal hemoglobinuria later this year and expect to read out pivotal results in generalized myasthenia gravis in the second half of next year.
We also initiated our Phase 3 program in geographic atrophy in dry age-related macro degeneration with initial patient screening now underway. We believe that our systemic approach has several significant advantages over currently approved agents. First, it may avoid the risk of rare but severe eye inflammation irreversible vision loss that has been observed with currently approved intravitreal treatments. And our systemic approach is the potential to offer convenient treatment of bilateral disease as well.
Regarding our Factor XI antibodies, we remain on track to report top line results by year-end of our proof-of-concept studies for our A2 domain targeting and our catalytic domain targeting antibodies in the setting of prevention of venous thromboembolism following the new replacement surgery. Results of these studies will inform whether to proceed to registration-enabling studies with one or both of these antibodies, with the possibility that both antibodies will advance to Phase 3, but in different thrombosis indications or in patient -- different patient populations.
In summary, we continue to drive forward our innovative development pipeline and anticipate reading out several pivotal and proof-of-concept data sets in oncology, immunology, obesity, hematology and genetic medicines over the next 12 to 18 months, while our early research engine has never been more productive with multiple novel programs potentially advancing into the clinic over the same time frame.
And with that, I will turn the call over to Marion.
