Dean Y. Li
Executive Vice President and President, Merck Research Laboratories at Merck & Co., Inc.
Thank you, Caroline. Today, I will provide notable updates since our last earnings call. We continue to make significant advancements and achieve important regulatory milestones. The fourth quarter marks the end of a successful year with progress made across oncology, vaccines, infectious diseases and cardiology.
Let me start with Oncology. We remain committed to transforming the landscape of cancer therapy with an ongoing focus on treating earlier stages of disease. We are pleased by the recent approval of KEYTRUDA for the adjuvant treatment of adult patients with stage IB, II or IIIA non-small cell lung cancer following resection and platinum-based chemotherapy based on the results of KEYNOTE-091. This approval provides, for the very first time, an adjuvant immunotherapy option for this patient population with stage IB disease and regardless of PD-L1 status.
Beyond KEYNOTE-091, we have additional ongoing studies in earlier stages of non-small cell lung cancer including, KEYNOTE-671 evaluating KEYTRUDA with platinum doublet chemotherapy as neoadjuvant followed by adjuvant therapy in resectable stage II, IIIA and IIIB disease, KEYNOTE-867 evaluating KEYTRUDA in patients undergoing stereotactic body radiotherapy with unresected stage I or II disease and KEYLYNK-012 studying KEYTRUDA in combination with Lynparza in stage III disease. These trials are all part of our broader effort to treat earlier stages of cancers and further improve patient outcomes across tumor types, such as melanoma.
Together with Moderna, we announced positive Phase 2 results for V940/mRNA-4157, in combination with KEYTRUDA, for the adjuvant treatment of stage III and IV melanoma in patients with high risk of recurrence following complete resection. The combination demonstrated a statistically significant and clinically meaningful improvement in recurrence free survival versus KEYTRUDA alone. This investigational personalized neoantigen therapy utilizes mRNA technology and is specifically tailored to target the unique mutational signature of each patient's tumor. We plan to discuss the results with regulators and initiate Phase 3 trials in multiple tumors this year. Detailed results will be presented at an upcoming medical meeting.
We also announced positive results from the Phase 3 KEYNOTE-966 trial evaluating KEYTRUDA in combination with chemotherapy. This trial demonstrated an improvement in overall survival for the first line treatment of patients with advanced or unresectable biliary tract cancer. In addition, we announced positive topline results from the Phase 3 KEYNOTE-859 trial evaluating KEYTRUDA in combination with chemotherapy for the first-line treatment of patients with HER2-negative locally advanced unresectable or metastatic gastric or gastro-esophageal junction adenocarcinoma.
In November, we announced the acquisition of Imago Biosciences, which closed last month. Imago's lead candidate, bomedemstat is a potentially first-in-class orally available lysine-specific demethylase 1 inhibitor. It is currently being evaluated in multiple Phase 2 clinical trials for the treatment of essential thrombocythemia, myelofibrosis and polycythemia vera. The combined team is now focused on continuing to advance the ongoing clinical development programs.
At the American Society of Hematology annual meeting, data were presented from multiple pipeline candidates including, favezelimab, our anti-LAG3 antibody; zilovertamab vedotin, an antibody drug conjugate, targeting ROR-1; nemtabrutinib, our oral reversible, non-covalent BTK inhibitor; as well as KEYTRUDA. Updated Phase 2 data for bomedemstat in essential thrombocythemia and advanced myelofibrosis were also presented.
We continue to deliver on our regulatory strategy. In the European Union, along with our partner, Astra Zeneca, we announced the approval for Lynparza, in combination with abiraterone and prednisone, for the treatment of certain patients with metastatic castration-resistant prostate cancer based on the results of the PROpel trial. In China, based on the results of KEYNOTE-522 and KEYNOTE-394, we received approvals for KEYTRUDA in neoadjuvant/adjuvant high-risk, early-stage triple negative breast cancer and hepatocellular carcinoma, respectively.
With our partners, Astellas and Seagen, we announced the FDA has accepted supplemental biologics license applications for KEYTRUDA with PADCEV, an antibody-drug conjugate targeting Nectin-4, for the first line treatment of certain patients with locally advanced or metastatic urothelial cancer, who are not eligible to receive cisplatin-containing chemotherapy. The agency set a PDUFA date of April 21, 2023 for each application.
Building on the clinical benefits observed with KEYTRUDA in combination with chemotherapy and antibody drug conjugates, we have focused on augmenting our tissue targeting candidates through business development. We announced the expansion of our agreement with Kelun Biotech with the addition of up to seven preclinical antibody drug conjugates. The collaboration leverages technology with the potential to yield a new generation of candidates designed to precisely target and deliver potent anticancer agents to the tumor site.
This follows previously disclosed agreements for two clinical stage candidates, including MK-2870, an investigational TROP2 targeting ADC we are planning to advance into Phase 3 trials this year. We also expanded our collaboration with PeptiDream to include the discovery and development of peptide drug conjugates. This technology potentially provides for improved permeability and drug selectivity in targeting tumor tissue.
Next to our vaccines portfolio, we were encouraged by the progress scientists and clinicians at the Instituto Butantan in Brazil made in developing a single dose dengue vaccine candidate for registration in Brazil. We are collaborating with the team there to conduct a detailed analysis of these positive, topline Phase 3 results to determine next steps for our own dengue vaccine candidate, V181, currently in Phase 2 development. Merck's goal is to make V181 available outside of Brazil for populations at-risk for dengue.
As Caroline noted, we are receiving positive feedback from the field regarding the recent launch of VAXNEUVANCE in the pediatric setting and remain confident in our population specific strategy for the prevention of pneumococcal disease. VAXNEUVANCE offers strong protection, including in the first year of life, with robust immunity across all shared and unique serotypes. This is important because the incidence of invasive pneumococcal disease is greatest in the first year of life for children. Also, we are on track and look forward to the Phase 3 results from our V116 program for the protection of adults this year.
We, along with others in the industry, are making a real impact in our goal to help reduce cancer incidence. It was noteworthy that the American Cancer Society's recently published annual report on cancer facts and trends included the remarkable observation that there has been a 65% reduction in cervical cancer incidence in women 20 to 24 years old, from 2012 through 2019. It is this type of finding that further reinforces Merck's commitment to bringing forward treatment and prevention options to help patients with this devastating disease. As part of this commitment, we are encouraged by the role GARDASIL continues to play in helping to prevent certain HPV related cervical cancers.
Turning to the broader portfolio. With the continued impact of COVID-19 in China, treatment options are urgently needed to help reduce the incidence of disease and burden on healthcare systems. We were pleased LAGEVRIO was granted conditional marketing authorization by China's National Medical Products Administration in December, for use in adult patients, who have mild to moderate COVID-19 infection and a high risk of progressing to severe cases.
I wish to reinforce something Rob mentioned. Please mark your calendars for March 6, where we will present detailed findings of the Phase 3 STELLAR trial evaluating sotatercept in patients with pulmonary arterial hypertension and the Phase 2 results for MK-0616, our oral PCSK9 inhibitor, at the American College of Cardiology in conjunction with the World Congress of Cardiology meeting in New Orleans. We will also host a live investor event to answer your questions.
We look forward to bringing sotatercept as an important treatment option to patients and are currently working towards submission of the data from the STELLAR trial. We are in discussions with the FDA about submission of the data on a rolling basis, which is likely to result in a potential approval in early 2024.
As we close out 2022, it is important to highlight that over the course of the year we made strong progress across therapeutic areas, modalities, stages of development and multiple business development transactions. In oncology, we obtained several important regulatory approvals globally for KEYTRUDA, and Lynparza; as well as advanced a number of programs evaluating earlier stage cancer regimens.
In vaccines, we received an important approval in pediatrics for VAXNEUVANCE. In addition, we were granted expanded authorizations in China and active recommendations were reinstated in Japan for GARDASIL. In HIV, we resumed our clinical development program for islatravir. And finally in cardiovascular disease, we made significant progress across our pulmonary arterial hypertension and hypercholesterolemia programs.
Taken together, we continue to deliver on our strategy of advancing promising candidates across multiple therapeutic areas. We have strong momentum across our pipeline and look forward to providing further updates on our progress in 2023.
And now, I will turn the call back to Peter.