George Yancopoulos
President & Chief Scientific Officer at Regeneron Pharmaceuticals
Thank you Len. I will start with ophthalmology today. At the recent Angiogenesis meeting, we presented encouraging results for the Phase II CANDELA study of aflibercept 8 milligrams in patients with wet AMD [Phonetic] primary safety end points with no new safety signals observed through week 44 and efficacy end points numerically favored aflibercept 8 milligrams in visual acuity, drying and other anatomical measures through week 44. Phase III studies, PHOTON in DME and PULSAR in wet AMD are ongoing. The primary objective of the Phase III studies is to determine whether aflibercept 8 milligram dosing can allow for more extended dosing intervals while maintaining efficacy and safety.
Regarding Phase III design in both PHOTON and the PULSAR study, patients are randomized at baseline to three groups: an every 8 week EYLEA 2 milligram arm, an every 12 week 8 milligram aflibercept arm and an every 16 week aflibercept 8 milligram arm following loading doses. The primary end point of both these studies is mean change in best corrected visual acuity, or BCVA at week 48. The primary end point will be met if 8 milligram aflibercept is not inferior to 2 milligram EYLEA while being dosed less frequently. We anticipate results of both PHOTON and PULSAR in the second half of this year and if positive, to file for regulatory approvals in the U.S. and EU by early 2023.
Moving to Dupixent which had a remarkable quarter in terms of clinical updates and regulatory progress, in January we announced our second positive Phase III study in prurigo nodularis, a disease with high unmet need. At the AAAAI and AAD meetings this year, we presented detailed data from the first positive Phase III study in prurigo nodularis and we also presented detailed data from our positive Phase III studies in eosinophilic esophagitis and in chronic spontaneous urticaria, or CSU, in biologic naive patients. The second Phase III CSU study in patients refractory to omalizumab did not reach statistical significance in an interim analysis and as announced in March, we have completed enrollment in the first of the two Phase III Dupixent studies in COPD and anticipate data from this first study to read out in the first half of next year.
In terms of regulatory progress, we expect an FDA decision for Dupixent in children aged six months to five years with moderate to severe atopic dermatitis by the new June 9 PDUFA date. We are also excited about an upcoming trial in collaboration with the National Institute of Allergy and Infectious Diseases, or the NIAID, to assess efficacy and safety of Dupixent for asthma in underserved populations, including Black and Hispanic children in the United States. Additionally, we are expecting an FDA decision for our supplementary BLA in eosinophilic esophagitis in patients 12 years and older by August 3 and we completed our regulatory submission for prurigo nodularis indication with FDA acceptance of this application anticipated shortly.
Moving to Libtayo and oncology, we are excited about the upcoming milestones in our oncology pipeline, including the FDA decision on our Libtayo chemo combination application for non-small cell lung cancer, data readouts and potential regulatory filings for our hematology bispecifics, as well as initial data readouts from our bispecific antibodies for solid tumors.
In hematology, Odronextamab, our CD20xCD3 bispecific has the potential for best-in-class efficacy in both follicular and diffuse large B-cell lymphoma and was recently granted fast track designation from the FDA for these indications. Detailed results of our first in human study were recently published in Lancet Hematology and our registration in 10 programs in late stage follicular lymphoma and DLBCL are expected to complete enrollment soon. Based on the safety profile we are observing from our updated step-up dosing regimen, we believe Odronextamab has the potential to be administered entirely within the outpatient setting. We look forward to filing with this updated data set later this year, pending regulatory feedback from the FDA.
Development of REGN5458, our BCMAxCD3 bispecific investigated for relapsed or refractory multiple myeloma, remains on track and pending regulatory feedback, we are planning to submit regulatory approval in the first half of 2023. Studies in earlier lines of the disease as well as an umbrella study in multiple myeloma investigating 5458 in combination with various standard of care products and investigational candidates will begin enrollment shortly.
The second half of the year, we anticipate initial clinical data disclosures for three first-in-class bispecifics: our MUC16xCD3 monotherapy for late stage ovarian cancer, our METxMET bispecific antibody for met-altered non-small cell lung cancer, as well as our PSMAxCD28 costim bispecific in combination with Libtayo in late stage prostate cancer. For these late stage cancers, patients have limited options and showing any durable response would be a promising early sign to be confirmed with additional clinical studies also involving combinations. We continue to progress our strategic approach to oncology which starts with Libtayo as our foundational anti-PD1 therapy and is augmented by logical combinations utilizing our broad oncology pipeline, whether it involves combining Libtayo with a second checkpoint inhibitor, as we are doing with our LAG-3 antibody in melanoma and other settings, with different combinations of bispecifics or with other agents in our portfolio.
Briefly turning to our antibodies against COVID-19, as we recently announced, the FDA extended its review of our REGEN-COV BLA for COVID-19 treatment and prophylaxis with a new action date of July 13. This extension was due to ongoing discussions with additional data provided to the FDA on pre-exposure prophylaxis use of REGEN-COV. As this regulatory process continues, we are advancing next-generation COVID-19 antibodies and initiated a first in human trial with a new candidate in April. We continue to believe that a major unmet need for COVID antibodies is in chronic disease prevention for immunocompromised patients and future development efforts will be addressing this population.
Concluding with our Regeneron genetics medicine, where we in collaboration are continuing to advance our pipeline. For our siRNA collaboration with Alnylam, we are very excited about our first-in-class approach to combining siRNA with antibody therapeutics designed to maximize effect as well as duration of target blockade. The first of these is our C5 siRNA antibody combination, cemdisiran plus pozelimab. Phase III studies of the combination treatment for paroxysmal nocturnal hemoglobinuria, or PNH and myasthenia gravis are underway and we'll be dosing patients shortly. In PNH, we are planning to test our combo in both naive and switch patients tested against standard of care therapies, including ravulizumab and eculizumab. Beyond C5, several additional combination programs are in our pre-clinical pipeline.
We continue to work with Alnylam as leaders in the use of siRNA therapeutics to address non-alcoholic steatohepatitis, or NASH, with several programs addressing novel targets discovered by the Regeneron Genetic Center. First data in NASH patients for ALN-HSD are anticipated mid-2022. We are progressing a second target, PNPLA3 into the clinic later this year and have recently identified an additional novel promising target that has been validated by RGC and is awaiting peer review publication. We are also pleased to report a novel milestone, that we and Alnylam initiated our first CNS target siRNA clinical program targeting amyloid precursor protein, or APP, in development for both cerebral amyloid angiopathy and Alzheimer's disease. Showing that this siRNA approach can reduce levels of the target protein in the CNS has the potential to open the door for using this approach in multiple genetically defined neurodegenerative diseases.
In the first quarter, we and Intellia provided an update on our joint CRISPR-based knockout program for transthyretin amyloidosis. Just to remind you, this is the first example of achieving CRISPR-based genomic editing in human beings. Our recent update demonstrated greater than 90% reduction of transthyretin durably achieved for the follow-up observation period in patients with hereditary transthyretin amyloidosis with polyneuropathy, as well as acceptable safety observed so far.
Our genetics medicine portfolio now includes a diverse pipeline of siRNA candidates that we are working on with Alnylam targeting diseases of the liver, the brain and the eye, as well as our CRISPR-based approaches in collaboration with Intellia and our bio-targeted gene delivery programs, such as with Decibel addressing congenital forms of hearing loss and other internal programs. While still early, we think these groundbreaking approaches have the potential to change the practice of medicine.
With that, I will turn the call over to Marion.
