Albert Bourla
Chairman and Chief Executive Officer at Pfizer
Thank you, Chris. Hello, everyone. I'm happy to report that Pfizer generated another solid performance in the third quarter, recording 130% operational revenue growth, compared with third quarter of 2020. When excluding direct sales and alliance revenues provided by our COVID-19 vaccine, we generated 7% operational revenue growth compared with the previous-year quarter. We also are raising our 2021 total company guidance for both revenues and adjusted EPS. While we are proud of our financial performance, we are even more proud of this financial results of what these financial results represent in terms of the positive impact we are having on human lives around the world.
In the first nine months of 2021, our innovative medicines and vaccines reached nearly a billion people. It's fair to say millions of lives have been saved because of this. Excluding our COVID-19 vaccine, we reached nearly 300 million people during that time. These are humbling numbers for all of us at Pfizer. At the same time, we delivered to our shareholders the 30 -- the 331st consecutive quarterly dividend. We also continue to advance our R&D pipeline. Some key milestones include the first COVID-19 vaccine authorized for emergency use in the US for children 5 to 11 years of age, the first patient dosed in our large Phase 3 RENOIR study for our RSV bivalent vaccine candidate and the initiation of Phase 2/3 studies for both IV and oral protease inhibitor candidates for COVID-19.
Let me start with commentary on some of our key growth drivers in the quarter, the biggest of which was Comirnaty, which contributed $13 billion in global revenues during the third quarter. To date, we have produced 2.6 billion doses and shipped 2 billion doses to 152 countries or territories. So far, 75% of our Comirnaty revenues have been generated outside the US, and we continue to sign agreements with governments around the world. We also remain on track to produce 3 billion doses this year, of which at least 1 billion will go to middle and low-income countries.
In addition, our weekly market share of COVID-19 vaccines administered continues to increase. In the US, our four week average market share increased from about 56% in April to about 74% as of October 31. And in the EU it went from about 70% to about 80% during the same time period. These market share increases are primarily the result of our booster being the first to receive emergency use authorization and our two-dose series being preferred by some countries around the world for use in certain younger populations.
We also continue to follow the science to help ensure we stay ahead of the virus. Let me speak to two examples: First, top-line results from our Phase 3 randomized, controlled trial demonstrated that a booster dose administered to individuals 16 years of age and older who previously received the Pfizer-BioNTech primary two-dose series restored vaccine protection against COVID-19 to the high levels achieved after the second dose. Second, the US Food and Drug Administration has authorized our COVID-19 vaccine for emergency use for children 5 through 11 years of age, the first and only vaccine to receive such authorization. For this age group, the vaccine is to be administered in a two-dose regimen of 10-microgram doses given 21 days apart. The 10 microgram dose level was carefully selected based on safety, tolerability and immunogenicity data.
Last week we announced that the US government exercised its final purchase option under the existing US supply agreement to purchase 50 million additional doses of Comirnaty. This brings the total number of pediatric doses purchased by the US government to 115 million, which is enough to vaccinate every US child. Overall, the US has now purchased a total of 600 million doses across all age ranges under this supply agreement.
Now let's take a look at some of the quarter's other key growth drivers. Eliquis has continued to deliver strong performance, with global revenues up 19% operationally to $1.3 billion in the third quarter. In the US, sales growth for Eliquis was driven mainly by a 16% growth in prescription volume. Vyndaqel and Vyndamax revenues were up 42% operationally to $501 million globally. Our disease education efforts in the US continued to support increases in appropriate diagnosis, while the main driver of growth in Japan has been the successful establishment of several referral networks in select areas resulting in new patient starts.
Ibrance continues outside of the US. Revenues outside of the US were up 9% operationally to $500 million. This growth was driven by accelerating demand as the delays in diagnosis and treatment initiations caused by COVID-19 show signs of recovery across several international markets. Global revenues for Ibrance were up only 1% operationally, as the international growth was largely offset by a 3% decline in the US. The US decline was driven by an increase in the proportion of patients accessing Ibrance through our Patient Assistance Program.
We continue to be pleased with the performance of our Oncology biosimilars portfolio, which is now the largest in the industry, with six biosimilars approved in the US for patients living with cancer. Global revenues from this portfolio grew 51% operationally during the quarter to $398 million. This growth was primarily driven by continued strong results from our US therapeutic monoclonal antibody launches. In International Developed Markets, Oncology biosimilars contributed 29% operational growth, driven by new launches of Zirabev and continued growth of Trazimera.
Of course, with such a broad portfolio of life-changing and life-saving products, it would be uncommon to not have a few challenges. US revenues for our Prevnar family, Prevnar 13 and Prevnar 20, for example, were down 2%, primarily due to a 36% decline in the adult indication of Prevnar 13 due to the ongoing prioritization of primary and booster vaccination campaigns for COVID-19 and a later start of the flu season compared with last year. Other contributing factors were the continued impact of the lower remaining unvaccinated eligible adult population and the June 2019 change to the Advisory Committee on Immunization Practices the change of ACIP recommendation for the Prevnar 13 adult indication to shared clinical decision-making.
Just two weeks ago, ACIP voted to recommend Prevnar 20 for routine use to help protect adults against invasive disease and pneumonia caused by the 20 Streptococcus pneumoniae serotypes in the vaccine. Specifically, the ACIP voted to recommend Prevnar 20 for adults aged 65 and older and adults aged 19 to 64 with certain risk conditions, without the need to be followed by PPSV-23 vaccination. This recommendation recognizes for the first time the significance of helping protect more populations under age 65 with co-morbid and immunocompromising conditions who are at increased risk of disease against these 20 disease-causing serotypes. This new 1-dose regimen option, once endorsed by the CDC Director, also will help simplify long-standing adult pneumococcal recommendations. As a reminder, Prevnar 20 is the only vaccine the FDA has approved not only for invasive pneumococcal disease but also for pneumonia.
In September, I'm sure many of you saw that the FDA issued a Drug Safety Communication related to its completed review of the Xeljanz ORAL Surveillance trial. We are in continuing dialogue with the FDA about its assessment and the resulting, final content in the Xeljanz label. With this important step taken, we hope we are a step closer to having an update regarding the new drug application for abrocitinib in atopic dermatitis and the supplemental NDA for Xeljanz in ankylosing spondylitis, both of which are currently under FDA review.
In terms of Xeljanz, its currently approved indications in the US, we believe that Xeljanz prescribing behavior will adjust in the coming months based on the FDA's update, resulting in an initial correction in the short-term. But based on the trends we have observed and the broad application of Xeljanz across its approved indications, we believe Xeljanz has the potential to return to growth again once a final US label is issued, and physicians have adjusted their prescribing habits accordingly as we go into 2022 and beyond.
Cibinqo, abrocitinib received marketing authorization for the treatment of moderate to severe atopic dermatitis in adults and adolescents aged 12 years and over from the UK Medicines and Healthcare products Regulatory Agency and the Japanese Ministry of Health, Labour and Welfare in both doses. It also received a positive opinion in adults from The European Medicines Agency's Committee for Medicinal Products for Human Use. We are hopeful this momentum will continue. We have applications currently filed for review with regulators around the globe, including in the US and Australia.
Overall, we remain confident in the importance of the JAK inhibitor class for appropriate patients with inflammatory diseases, and we are pursuing a variety of options for advancing additional JAK inhibitor assets within our portfolio. For example, Pfizer has granted an exclusive license to brepocitinib and TYK2, both in Phase 2 development, to a new company formed in collaboration with a partner that has a proven track record in late-stage Inflammation & Immunology drug development. The new company will direct all future development decisions, while Pfizer will have a 25% stake and retain certain ex-US commercial rights for brepocitinib and TYK2. This transaction will enable the allocation of resources to advance development of brepocitinib and TYK2 while allowing Pfizer to focus on diversifying its pipeline.
Another way in which we are continuing to bolster our pipeline is through strategic business development agreements. This slide highlights ten such agreements we have entered into in recent years, spanning four different therapeutic areas. To further build on our strength in cancer research we acquired Array Biopharma. The team in Boulder, Colorado, has become a center of excellence for targeted therapies in not only cancer but other diseases as well with an expected one to two new compounds entering the clinic each year.
Leveraging our strengths in gene therapy, we entered into a collaboration with Vivet Therapeutics for a potential gene therapy for Wilson Disease, a rare, genetic disorder that can cause severe hepatic damage, neurological symptoms, and potentially death. Our acquisition of Therachon builds on our Rare Disease team's 30-year commitment to develop innovative medicines that address significant unmet medical needs of people with rare diseases.
Regarding our worldwide exclusive licensing agreement with Akcea, we believe our expertise and breadth of experience in cardiovascular and metabolic diseases makes us well suited to accelerate clinical development of AKCEA-ANGPTL3-LRx, an investigational antisense therapy being developed to treat patients with certain cardiovascular and metabolic diseases.
We are excited about our collaboration with Valneva to develop and commercialize Valneva's Lyme disease vaccine candidate, VLA15, the only active Lyme disease vaccine program in clinical development today. Of course, our collaboration with BioNTech on a COVID-19 vaccine led to the first mRNA vaccine ever approved, and this relationship was born out of our companies' initial collaboration to develop an improved flu vaccine based on mRNA tech.
Building on our strengths in prostate cancer and women's health, we have entered into an agreement with Myovant to jointly develop and commercialize Orgovyx, relugolix, in advanced prostate cancer and relugolix combination tablet in women's health in the US and Canada. Our global collaboration with Arvinas to develop and commercialize ARV-471, an investigational oral PROTAC estrogen receptor protein degrader, builds on our metastatic breast cancer franchise, allowing us to potentially go into earlier non-metastatic patients and add to efficacy of Ibrance in a metastatic setting.
Trillium's CD47/SIRP-alpha focused technology has the potential to be as foundational in cancer immunotherapy as PD-1/PD-L1s have been. We look forward to that acquisition closing later this year and in the first half of 2022. With three approvals, four EUAs and multiple submissions and readouts, these transactions are already bearing fruit and positioning us to reach even more patients.
Before I close, I want to welcome to the call Aamir Malik, who joined us in August as Executive Vice President and Chief Business Innovation Officer. Aamir came to us from McKinsey, where during his 25-year career, he has developed growth strategies, guided mergers and acquisitions, and implemented large-scale programs to improve patients' lives and transform performance for life science companies. This includes working closely with Pfizer on several strategic initiatives. I have known Aamir for more than 15 years, and I am certain he will be an incredible addition to Pfizer as we look to the next era of innovation.
Looking ahead, we continue to focus on driving operational excellence across the organization and pursuing the kinds of first-in-class science that will define the New Pfizer. Given our third quarter performance and our current expectations for the near term, we continue to expect a revenue CAGR of at least 6%, on a risk-adjusted basis, through the end of 2025 and double-digit growth on the bottom line. I would remind you that these projections do not include any potential impact from Comirnaty, recent or subsequent business development activities, or potential future mRNA programs. Rather, we remain very confident in our ability to achieve these growth rates because of the strength of our current product portfolio and R&D pipeline.
Now I'll turn it over to Mikael to speak more about our R&D efforts and then Frank will provide financial details on the quarter and our outlook for the remainder of 2021 which looks solid. Mikael?
