Dean Y. Li
Executive Vice President and President, Merck Research Laboratories at Merck & Co., Inc.
Thank you, Caroline. Good morning, everyone. It is a pleasure to be here to provide a summary of progress made since our last quarter call. I will provide an update on our oral antiviral candidate molnupiravir, highlight the proposed Acceleron acquisition, spotlight some recent progress with islatravir and finish with a synopsis of notable regulatory milestones and clinical updates from across the pipeline.
The need for additional treatment options remains key in combating the COVID-19 pandemic. Interim analysis from MOVe-OUT, our Phase 3 study evaluating molnupiravir in at-risk non-hospitalized patients with mild-to-moderate COVID-19 showed an approximately 50% reduction in the risk of hospitalization or death compared to placebo. Of note, through Day 29 no deaths were reported in patients who received molnupiravir compared to eight deaths on placebo. This is the first oral antiviral for a respiratory virus to demonstrate benefit based on robust clinical outcomes and the first to show a meaningful five-day window for therapeutic intervention after symptom onset. Based on these positive results and at the recommendation of the Independent Data Monitoring Committee and in consultation with the FDA, recruitment in this study was stopped early. In light of these findings and given the urgency to address the pandemic, our team has worked tirelessly to submit a robust package to the FDA for EUA within 10 days of receiving data. We look forward to discussing the EUA submission at an upcoming meeting of the Antimicrobial Drugs Advisory Committee scheduled for November 30, and in the interim, we continue to engage with the FDA to support its review. Applications that's also been submitted to multiple regulatory agencies around the world.
I do wish to take a moment to thank the investigators, patients and their families for their participation in the MOVe-OUT study. I am also grateful to our collaborators at Emory University, Ridgeback and Merck's internal teams for the incredible work done in conducting this program during a very challenging time. A comprehensive vaccination strategy remains the best sustainable needs to confront this COVID-19 pandemic. Timely intervention following symptom onset with an oral agent that can be self-administered at home may provide an additional meaningful option for patients, healthcare systems and public health, which could make a significant and positive impact on the pandemic.
Based on available viral sequence data, molnupiravir showed consistent efficacy against the Gamma, Delta, and Mu COVID-19 variants. As a reminder, we continue to actively recruit participants in the MOVe-AHEAD trial, which is evaluating the safety and efficacy of molnupiravir and preventing the spread of COVID-19 within households as a post-exposure prophylactic with a planned readout in the spring of 2022.
Now, turning to the proposed Acceleron acquisition. Acceleron has an excellent scientific pedigree, which has yielded important treatment for anemia in adult patients with certain rare blood disorders. Their lead clinical candidate, sotatercept, has the potential to be a foundational asset as an add-on therapy for the treatment of pulmonary arterial hypertension and provide a complementary addition to our growing cardiovascular pipeline. As such, following the close of the deal, our strategy would be to advance the wide-ranging Phase 3 clinical program.
Now, onto the portfolio on pipeline, starting with HIV. We continue to generate clinical data that reinforces the foundational potential islatravir in HIV. At the European AIDS Conference in London this week, we presented data from the Phase 2 study evaluating doravirine and islatravir in previously untreated adults with HIV infections, which demonstrated continued maintenance on viral suppression through 144 weeks. We also recently reported positive top line results from two pivotal trials evaluating a once-daily oral regimen of doravirine and islatravir in a switch setting in adults with HIV infection who are very logically suppressed on other HIV therapy regimen. At 48 weeks, both trials met their primary efficacy endpoint for percentage of participants with levels of HIV RNA greater than or equal to 50 copies per milliliter, demonstrating comparable efficacy with those receiving the comparator anti-retroviral therapy. We plan to present these findings in the upcoming medical congress and incorporate the data into global regulatory submission.
This week, we also announced the start of a Phase 2 clinical study evaluating a once-weekly oral combination of islatravir and lenacapavir in people living with HIV who are virologically suppressed on an anti-retroviral therapy. We have made great progress in our collaboration with Gilead and look forward to reporting on future developments, including our long-acting injectable co-formulation.
Next, on to VAXNEUVANCE. We received a positive opinion for VAXNEUVANCE from the European Medicines Agency's Committee for Medicinal Products for Human Use an individual 18 years of age and older. And more recently in the US, the CDC's ACIP voted unanimously to provisionally recommend VAXNEUVANCE followed by PNEUMOVAX as an option for pneumococcal vaccination in adults 65 years and older, as well as for adults aged 19 to 64 with certain underlying medical conditions with both patient population being studied in our clinical trial. Vaccine performance is multi-dimensional and includes eliciting a strong immune response, as well as providing coverage for important disease serotypes. Our two dose regimen accomplishes the best of both by eliciting a robust immune response across the 15 serotypes in VAXNEUVANCE, including serotype 3, as well as providing the broader serotype coverage among current pneumococcal vaccine options, of which four that are unique to PNEUMOVAX. Furthermore, VAXNEUVANCE vaccines that has the most extensive clinical development program of the newly licensed PCVs. This includes completed or ongoing evaluations among those with certain chronic or immune-compromised conditions that increase susceptibility 2 and severity of pneumococcal disease.
We also announced positive top line results for VAXNEUVANCE from the pivotal PNEU-PED study evaluating immunogenicity, safety and tolerability in the pediatric setting and have submitted an application to the FDA. Evidence indicates the incorporation of serotypes 22F and 33F, as well as strong immunogenicity against serotype 3 has the potential to play an important role in the prevention of pneumococcal disease in infants and children. These three serotypes represent more than a quarter of all cases of invasive disease in children under the age of 5. We will present full results at an upcoming scientific congress.
And finally to Oncology, the rich flow of data from our clinical development programs across tumor type continue. We maintain momentum in the development of new treatment options for women's cancer with the approval of KEYTRUDA plus chemotherapy with or without bevacizumab, for recurrent or metastatic cervical cancer based on data from KEYNOTE-826. This study showed a meaningful 36% reduction in the risk of death. This is the first anti-PD-1 combination treatment option for patients in the first-line setting, and together, with our industry-leading human papillomavirus vaccine GARDASIL and GARDASIL 9, we are uniquely positioned to address certain unmet need in cervical cancer with a focus on both prevention and treatment.
At ESMO in September, we presented final results on KEYNOTE-355, our study of KEYTRUDA in combination with chemotherapy for advanced triple-negative breast cancer, which show the reduction in the risk of death by 27%. KEYTRUDA is the only immuno-oncology agent approved in metastatic triple-negative breast cancer. This, along with additional data presented across endometrial and ovarian cancers, reinforces the remarkable progress being made in our broad women's cancer portfolio.
We are also making inroads the new cancer types, including prostate cancer. With our partners at AstraZeneca, we announced positive results from the Phase 3 PROpel study for the front-line treatment of metastatic castration-resistant prostate cancer. This study demonstrated that LYNPARZA in combination with abiraterone significantly delayed disease progression regardless of biomarker status. LYNPARZA is the first PARP inhibitor to demonstrate clinical benefit in radiographic progression-free survival in combination with a new hormonal agent in this setting. We are encouraged by this study and the potential to help the increasing number of men diagnosed with metastatic castration-resistant prostate cancer. Results will be presented at an upcoming medical meeting and submitted to regulatory authorities globally.
Next, to renal cell carcinoma, which represents an important area of expansion. In August, we received FDA approval for WELIREG, a first-in-class HIF-2 alpha inhibitor therapy for the treatment of adult patients with Von Hippel-Lindau disease require therapy for associated renal cell carcinoma, central nervous system and angioblastomas, or pancreatic neuroendocrine tumors, not requiring immediate surgery. This approval provides us a beachhead as we evaluate WELIREG potential in broader RCC indications and beyond. Also in RCC in partnership with Eisai, following FDA priority review, we received approval for the combination of KEYTRUDA and LENVIMA in the front-line setting based on results from the KEYNOTE-581 trial. This brings forth an important new first-line treatment option for patients with advanced RCCs.
We are also rapidly expanding programs into earlier lines of therapy. During the quarter, the FDA granted priority review for our application for KEYTRUDA as an adjuvant therapy for patients with RCC at intermediate high or high-risk of recurrent following nephrectomy or following nephrectomy and resection metastatic lesions from the KEYNOTE-564 study. Additionally, we received priority review for KEYTRUDA for the treatment of patients with surgically resected high-risk Stage 2 melanoma based on results from the KEYNOTE-716 study that showed an improvement in recurrent-free survival compared to placebo. Both of these studies demonstrate the benefit of expanding the use of KEYTRUDA to earlier stages of disease, allowing us to extend treatment benefits and more patients sooner. We look forward to a decision on both studies by the end of the year.
To conclude, I am proud of the progress across our broad pipeline and look forward to providing further updates on our scientific progress in the future.
Now, I turn the call back to Peter.