George D. Yancopoulos
Scientific Founder, President, Chief Scientific Officer and Director at Regeneron Pharmaceuticals
Thank you, Len. I'll pick up where you left me with the REGEN-COV story. As Len mentioned, our robust COVID-19 development program involving more than 25,000 people to date has provided compelling evidence that REGEN-COV has the potential to be used for various prevention and treatment applications from pre-exposure prophylaxis to treating hospitalized patients. In the United States, REGEN-COV is currently authorized under an EUA and also being reviewed for full FDA approval for the treatment and prevention of COVID-19 in certain patients with an action date of April 13, 2022. At Regeneron, we all appreciate that widespread vaccination is the best way to broadly protect as many people as possible from COVID-19. But recent research also reveals some important gaps in coverage provided by the vaccines, leaving some individuals uniquely vulnerable, particularly the several million immunocompromised people in the United States alone who remain prisoners of the pandemic. First, many of the immunocompromised population respond sub-optimally or not at all to vaccination, even after booster shots. Second, breakthrough infections in the general population still occur after vaccination, meaning that immunocompromised people will continue to be at risk of encountering infected individuals even within a highly vaccinated population. Therefore, we believe that REGEN-COV could be of particular importance for these immunocompromised individuals who remain unprotected and also are at highest risk for developing the most severe COVID-19 disease. This includes people with certain hematologic cancers, for example, lymphomas, leukemias and myeloma and people who take certain immunosuppressive medicines for diseases such as multiple sclerosis, in rheumatoid arthritis, for organ transplant recipients and for those with primary immunodeficiencies.
In the United States, Regeneron submitted data and a request to the FDA to expand the existing emergency use authorization of REGEN-COV to include chronic prevention back in April. Further reflecting Regeneron's commitment to the immunocompromised, we recently began a big trial to optimize REGEN-COV prophylaxis in this population, including evaluation of extended dose. Our current REGEN-COV cocktail retains potent activity against all known variants of interest, including the Delta variant. However, the virus continues to mutate and evolve. And thus, as we have previously discussed, we are advancing a novel anti-spike protein antibody cocktail into clinical development. We have done so proactively in the case of a novel innovative antibody cocktail that retains potency against new potential variants as required in the future. Moving to Ophthalmology. We reported encouraging top line data of high-dose aflibercept in the Phase II CANDELA study in wet AMD. The small proof-of-concept study met its primary efficacy endpoint, a higher proportion of patients in the eight-milligram aflibercept group had no retinal fluid compared to patients treated with the currently approved two-milligram EYLEA dose at week 16. There were no safety signals observed in the comparison to the currently approved EYLEA two-milligram dose, two large Phase III trials in wet AMD and DME, evaluating the high dose of aflibercept in dosing intervals of every 12 weeks and every 16 weeks are fully enrolled and are expected to report results in the second half of 2022. These Phase III data will be crucial to understanding overall efficacy, safety and convenience of high dose aflibercept.
Moving on to Dupixent. The remarkable clinical success of Dupixent across so many different allergic or type two inflammatory diseases, validates our early and long-standing hypothesis that these conditions are all driven by overactivation of the same fundamental immunologic pathway that is the interleukin-four and interleukin-13 pathway, which is effectively blocked by Dupixent whether the disease manifests as asthma or chronic [rhinositis] with nasal polyps in the airways as atopic dermatitis or prurigo nodularis in the skin, as the eosinophilic esophagitis in the GI tract. Our clinical data have demonstrated an important impact of Dupixent on these many conditions that initially did not seem related. In only the past few months, Dupixent demonstrated positive results in four separate pivotal studies. This is a tremendous accomplishment stemming from the vision and dedication of our team and it's great news for patients suffering from these type two inflammatory diseases. In a recent Phase III trial in atopic dermatitis in infants and children as young as six months of age, Dupixent met all primary and secondary endpoints as well as a lower observed rate of skin infections in the Dupixent group compared to placebo. Detailed results from this trial will be presented at a future medical meeting, and data will be submitted to the FDA by the end of this year. These data reinforce the well-established efficacy and safety profile of Dupixent with over 0.5 million patients treated to date. We also reported recent Phase III data with Dupixent in eosinophilic esophagitis or EoE, a progressive disease that damages the esophagus and impairs the ability to swallow. More than 1/3 of the patients in our trial had manifestations of this disease so severe that they previously had to undergo endoscopic dilation of the esophagus for symptomatic relief. In our study, patients taking weekly Dupixent had an approximate 24-point improvement on the 0 to 84 dysphagia symptom questionnaire, representing a 64 percent improvement compared to a 14-point improvement for placebo.
This update reinforced previously reported Phase III results for which the 52-week follow-up results were recently presented at the United European Gastroenterology Week Virtual 2021 Congress. Completion of our regulatory filing for EoE in adolescents and adults is planned for early 2022. We also recently reported positive results for Dupixent from our Phase III trial in yet another inflammatory skin condition known as prurigo nodularis, an underdiagnosed disease characterized by extreme itch and skin nodules. The trial met its primary and all key secondary endpoints in comparison to placebo, including reduction in itch from baseline at 12 and 24 weeks, achieving clear skin and improvement in quality of life. A second trial in prurigo nodularis is fully enrolled and is expected to read out in the first half of '22 with regulatory submissions planned for the same year. If all these exciting Phase III data lead to regulatory approvals, Dupixent would be approved for six different allergic or type two inflammatory disease indications, including patients as young as six months. Moving to Libtayo in Oncology. Positive Phase III data of Libtayo in combination with chemotherapy in first-line advanced non-small cell lung cancer were presented at the ESMO 2021 meeting. These data mark Libtayo as one of only two PD-1 or PD-L1 inhibitors to demonstrate positive Phase III results in first line non-small cell lung cancer, irrespective of histology, both as monotherapy and in combination with chemotherapy. These Libtayo studies were conducted in a patient population that included difficult-to-treat disease characteristics that reflects everyday clinical practice. We are rapidly progressing towards regulatory submission for the Libtayo chemotherapy combination across histologies and PD-L1 expression levels, which could unlock an opportunity to help a larger population of lung cancer patients.
Turning to Hematology. At the upcoming American Society of Hematology Annual Meeting for ASH, we will provide updates to our developing Hematology portfolio. The nodal presentation we will provide a data update for our potentially registrational first-in-human trial of REGN5458. Our BCMA by CD3 bispecific antibody tested in patients with heavily pretreated multiple myeloma. REGN5458 to be a major advance in treatment of patients who have failed several prior lines of therapy, but the potential utility of our BCMA-targeted bispecific is not limited to this patient population. We will discuss our data and further development plans at our virtual ASH Investor event scheduled for Monday, December 13 regarding odronextamab or CD20 by CD3 bispecific. We are pleased with our -- with recruitment in our potentially pivotal trial since the partial clinical hall was lifted earlier this year. Exploration of subcutaneous formulation of odronextamab is on track to start by the end of this year. We are planning to initiate broader Phase III programs in 2022. Our bispecific development program for solid tumors is progressing with our unique approaches, including the MUC16 timesCD3 bispecific as monotherapy in ovarian cancer as well as in combination with Libtayo or with our MUC16 timesCD28 costim. In addition, we expect to have initial data with our PSMAxCD28 costim in patients with prostate cancer in '22. We are also excited about our EGFRxCD28 costim clinical program across multiple EGF high cancer settings, including lung cancer as well as our clinical stage METxMET bispecific and our METxMET antibody drug conjugate, presenting a new [Indecipherable] for Regeneron into the realm of drug conjugates linked to our potentially best in class bispecific antibodies. In conclusion for Oncology, we are approaching an important new phase for Regeneron. We have several novel Phase I/II programs in clinical development with more expected in the coming months. We also have large Phase III studies planned such as our LAG-three Libtayo for first-line advanced melanoma against the pembrolizumab monotherapy comparator as well as large registrational programs for our Hematology/Oncology bispecifics. We're excited about the potential that these important investments in our portfolio may bring to patients.
I would like to conclude with our Regeneron genetics medicines in our collaboration updates. We are uniquely positioned to combine products of our established biologics portfolio and emerging findings from our genetics medicine efforts. As part of our collaboration with Alnylam, we are looking forward to multiple updates on our C5 program. As we already mentioned ASH meeting, we will show first-in-human data for our C5 antibody, pozelimab in combination with the C5 inhibiting siRNA, cemdisiran. We will present initial results in healthy volunteers, which supports development of this first-of-its-kind combination of an antibody and an siRNA therapeutic. Early data on siRNA monotherapy mediated C5 [Indecipherable] did not achieve complete terminal complement blockade, which is necessary for adequate disease control in PNH or paroxysmal nocturnal hematuria. Adding the antibody specific for the same target protein could provide patients with a lower dose therapy and a more convenient extended dosing regimen while providing more complete C5 inhibition, resulting in better efficacy and less breakthrough hemolysis. We have also recently initiated a Phase III study testing the C5 antibody and siRNA combination in myasthenia gravis. For PNH, starting next year, we are planning to test our combo in both naive and switch patients tested against standard of care therapies, including ravulizumab and eculizumab. This study has the potential to show a true benefit of the combination approach for the treatment of this disease. Also in collaboration with Alnylam, some of our initial genetic target discoveries are reaching the stage of clinical readouts for nonalcoholic steatohepatitis or NASH, a disease where finding compelling treatment options has been difficult. We're using the siRNA approach to silence the gene we identified as a potential target. Recall, we discovered that people with a protective HSD17B13 gene variant have a 30 percent to 70 percent lower odds of chronic liver disease. Our collaborator, Alnylam, will show initial healthy volunteer safety data for the Alnylam HSD, the HSD17B13 targeting siRNA at their upcoming R&D Day later this month. Finally, in October, the Regeneron Genetics Center published a manuscript in nature, which highlighted achievement of the milestone of sequencing almost 0.5 million exomes from the U.K. Biobank database. This nature paper for the first time describes rare variants of genes that could be potential drug targets for diseases such as hypertension, diabetes, asthma and others.
And with that, I will turn the call over to Marion.