George Yancopoulos
President and Chief Scientific Officer at Regeneron Pharmaceuticals
Thank you, Lynn. I'll start with ophthalmology. Positive pivotal results for aflibercept 8 milligrams in the PULSAR and PULSAR studies we recently presented at the American Academy of Ophthalmology Annual Meeting. The results of these trials in wet AMD and DME, respectively, demonstrated that a remarkably high percentage of patients were able to be rapidly initiated into and then successfully maintained through week 48 on 12- and 16-week dosing intervals. While achieving vision gains that were not inferior to the current standard of care, EYLEA 2-milligram dose every 8 weeks. These results suggest that aflibercep 8 milligrams has the potential to become the new standard of care in these retinal diseases.
I think it would be helpful if we step back for a minute and try to put these results in context. While what our trials did was push the limits far beyond what has been accomplished with any currently available anti-VEGF therapies. Rather than using response criteria to try to identify or slowly extend patients to longer dosing intervals, our trials tested whether all patients could be randomly assigned and rapidly initiated on extended dosing intervals of aflibercep 8-milligram without compromising visual improvement or safety. These aflibercep 8-milligram trials accomplished just that for the vast majority, while delivering a safety profile consistent with that of EYLEA. 89% of DME patients and 77% of WED AMD patients were able to be rapidly initiated and maintained on a 16-week of aflibercep 8-milligram dosing regimen, while 93% of DME and 83% of wet AMD patients we're able to be rapidly initiating maintained on at least a 12-week dosing interval, all while delivering efficacy similar to that of EYLEA administered every 8 weeks.
We believe these are truly unprecedented and potentially game-changing results, which have not been achieved using any other anti-VEGF agent. Now this has speculated that our PULSAR and PHOTON results were due to our dose modification criteria and even try to theoretically extrapolate that their agent could have somehow approached these results using our criteria. We put these speculative extrapolations into the category of wishful thinking. And based on our expert analysis of the data, we conclude it is all about the drug and not the trial design.
Briefly moving on to Dupixent. Building on our recent approval in eosinophilic esophagitis in adults and adolescents, we are planning on submitting a supplementary BLA for eosinophilic esophagitis in 1 to 11-year-old children in mid-2023. Dupixent ability to treat eosinophilic esophagitis highlights how important it is that our IL-4 and IL-13 blocker more completely targets the entire type two inflammatory cascade and not only eosinophils.
As you heard Len mentioned, the FDA label was expanded yet again in the third quarter as Dupixent became the first and only treatment indicated for prurigo nodularis, a debilitating chronic skin disease. This marks the fifth disease for which Dupixent is now approved. Our collective clinical data with Dupixent support a unifying molecular mechanism underlying these related diseases from asthma to atopic dermatitis to nasal polyps to prurigo nodularis to eosinophilic esophagitis. In this unifying hypothesis, IL-4 and IL-13 induced inflammation is driving all of these related diseases in different tissue compartments.
Moving to Libtayo in oncology. In the third quarter, our robust oncology pipeline has started to deliver data readouts from our latest and most innovative programs and we are expecting these readouts to accelerate in the remainder of 2022 and continuing to 2023. The European Society of Medical Oncology, or ESMO Annual Meeting in September, was truly a banner event for Regeneron with several notable oral presentations for assets in our oncology pipeline, which I'd like to briefly summarize.
Starting with fianlimab, our LAG-3 antibody in combination with Libtayo. At ESMO, we shared data from two independent advanced melanoma expansion cohorts from our first-in-human study, which importantly showed consistent efficacy and safety between the two replicate cohorts. Fianlimab, in combination with Libtayo demonstrated greater than 60% response rates in each cohort, a median PFS estimated to be 24 months across both cohorts and a median duration of response that had not yet been reached. The preliminary safety profile of the combination appears to be in line with anti-PD-1 monotherapy and potentially with less toxicity compared to anti-CTLA-4 combinations.
While dual LAG-3 and PD-1 inhibition has previously shown promise in advanced melanoma, response rates greater than 45% with median PFS of more than a year had not been previously reported. These initial results in melanoma suggest that fianlimab-Libtayo combination has a potentially best-in-class profile in this setting. We are enrolling our Phase 3 metastatic melanoma study -- we intend to initiate a Phase 3 adjuvant melanoma study later this year and have additional plans in other solid tumors where fianlimab has the potential to be first-in-class.
In neoadjuvant cutaneous squamous cell carcinoma, or CSCC, a Phase 2 study of Libtayo monotherapy has shown promising results. Given prior to potentially curative surgery in patients with large tumors, Libtayo was able to deliver major pathological responses to 63% of patients prior to surgery. This raises the possibility that Libtayo could decrease the burden of these major and potentially disfiguring surgeries for the many patients who require them each year. We are pleased that concurrent with the ESMO presentation, these data were published in the New England Journal of Medicine.
Regarding next steps, we are talking to regulators about possible pathways for labeling and potential inclusion in the NCCN guidelines. Also at ESMO, we presented initial clinical data for ubamatamab, our MUC16xCD3 bispecific developed for advanced ovarian cancer. Our first clinical data for a CD3 bispecific in a solid tumor. In a heavily pretreated ovarian cancer population, we observed durable responses to this MUC16xCD3 monotherapy in a patient subset whose tumors overexpressed MUC16, response rates were as high as 31%. Most of the treatment of Vergent [Phonetic] adverse events occurred with the initial step-up dosing. Ubamatamab is being developed as a monotherapy as well as in combination with Libtayo as well as in combination with our MUC16 costim bispecific. We are looking forward to more data across these programs in 2023.
In our ESMO investor presentation, we shared more detailed data for PSMAxCD28 costim bispecific in combination with Libtayo representing the first efficacy and safety data for this new class of bispecifics, which we had initially top-lined and discussed at our second quarter earnings. We have since continued to enroll patients in this study, and we are planning to present updated data at a medical meeting in the first half of 2023.
Regarding our hem/onc pipeline, we are looking forward to data from odronextamab, our CD20xCD3 bispecific as well as limboseltamab, our BCMAxCD3 bispecific at the American Society of Hematology or ASH Annual Meeting in December. For otrenixtimab, we will present pivotal Phase 2 data for both follicular lymphoma and diffuse large B-cell lymphoma in two separate oral presentations. Upon discussions with the FDA, we are now targeting a second half 2020 regulatory filing for this program. We hope to initiate combination studies with an appropriate CD20 costim bispecific in the near future.
For limbaceltumab, our BCMAxCD3 bispecific antibody remained on track with development and are planning to file pending discussions with the FDA in 2023. We have now completed enrollment in our potentially pivotal Phase 2 study. As I mentioned earlier, data from this study will be updated at ASH.
As with otrenixtimab, we are planning on initiating combination studies for limboseltumab with costimulatory bispecifics in the near future. We believe existing standard-of-care therapies leave significant room for improvement in these difficult-to-treat settings, and we have been encouraged by the interim efficacy and safety data we have generated to date for both odronextamab and limboceltimab.
Finally, at ESMA, we also shared initial data for our METxMET bispecific antibody in MET-altered non-small cell lung cancer. Responses were enriched in patients with higher levels of met expression. No dose-limiting toxicities were observed. Even the modest overexpression of MET may render lung cancer susceptible to this mechanism of action and we're looking forward to the METxMET antibody drug conjugate data next year.
In summary for oncology, a rich commentatorial pipeline is delivering competitive data. And with our full ownership of Libtayo, we're excited about the potential to advance standard of care in oncology with our portfolio approach.
Concluding with the Regeneron Genetic Medicines efforts, where we continue to progress our pipeline and discovery engine. In September, we and Alnylam reported promising data from our ongoing Phase 1 study of Alnylam HSD in nonalcoholic steatohepatitis or NASH. We are planning on initiating a Phase 2 study shortly, which is just one part of our multipronged approach, exploring multiple genetically validated targets for NASH.
Also in September, we and Intellia announced initial data from the cardiomyopathy arm of our ongoing Phase 1 study of NTLA-2001, an investigational CRISPR-based therapy for the treatment of transthyretin amyloidosis, which show deep and sustained mean serum TTR reductions of over 90% and was generally well tolerated. Finally, in October, our collaborators a Decibel Therapeutics announced FDA clearance for an NDA application for DB-OTO, our first virally delivered gene therapy product candidate designed to provide hearing to individuals with autoferalin-related hearing loss. This IND provides clearance to initiate a pediatric Phase 1/2 clinical trial in the United States.
With that, I will turn it over to Marion.
