Pfizer – Building on COVID-19 – PharmaLive

The pharmaceutical giant, still riding high on the sales of Comirnaty and Paxlovid, is looking to a future of innovative oncology drugs and vaccines based on mRNA technology.

By Christiane Truelove • [email protected]

 

Pfizer

235 East 42nd Street
New York, New York 10017 

212-733-2323 • pfizer.com

Financial Performance
	2021	2020	1H 2022	1H 2021
Revenue	$81,288	$41,651	$53,402	$33,415
Net income	$21,979	$9,159	$17,769	$10,440
Diluted EPS	$3.85	$1.63	$3.66	$2.01
R&D expense	$13,829	$9,393	$5,116	$4,233
All figures are in millions of dollars, except EPS.

Best-selling products

All sales are in millions of dollars.

• Comirnaty = Direct sales and
  alliance revenue
• Eliquis = Direct sales and alliance revenue
• Enbrel = Sales outside United States and Canada
• Xtandi = Alliance revenue

2021 sales

• Comirnaty $36,781 
• Eliquis $5,970 
• Ibrance $5,437 
• Prevnar family $5,272 
• Xeljanz $2,455 
• Vyndaqel/ Vyndamax $2,015 
  
• Enbrel $1,185 $
• Xtandi $1,185 
• Inlyta $1,002 
• Sulperazon $683 
• Sutent $673 
• Inflectra/Remsima $657 
• Premarin family $563 
• Bosulif $540

1H 2022 sales

• Comirnaty $22,075 
• Paxlovid $9,585 
• Eliquis $3,537 
• Prevnar family $2,994 
• Ibrance $2,557 
• Vyndaqel/ Vyndamax $1,164
  
• Xeljanz $802 
• Xtandi $558
• Enbrel $537 
• Inlyta $508 
• Sulperazon $420 
• Zirabev $286 
• Bosulif $284 
• Inflectra/Remsima $272 
• Premarin family $217 

Outcomes Creativity Index Score: 31

• Manny Awards — 2
• Cannes Lions — 2
• Clio Health — N/A
• Creative Floor Awards — 14
• London International Awards – N/A
• MM+M Awards — 13
• One Show — N/A

 

For Pfizer, COVID-19 spurred the company into greater innovation and profitability. The development of an effective vaccine and therapy for SARS-CoV-2 was a gamble — but it was a gamble that did pay off.

“In the early days of the COVID-19 pandemic, we committed to use all of the resources and expertise we had at our disposal to help protect populations globally against this deadly virus, as well as to offer treatments to help avoid the worst outcomes when infections do occur,” says Albert Bourla, CEO of Pfizer. “We put billions of dollars of capital on the line in pursuit of those goals, not knowing whether those investments would ever pay off. Now, less than two years since we made that commitment, we are proud to say that we have delivered both the first FDA-authorized vaccine against COVID-19 (with our partner, BioNTech) and the first FDA-authorized oral treatment for COVID-19.”

The company introduced the COVID-19 vaccine Comirnaty with partner BioNTech, and Paxlovid as the first FDA-authorized oral treatment for COVID-19.

“These successes have not only made a positive difference in the world, but I believe they have fundamentally changed Pfizer and its culture forever,” Bourla says. “Everywhere I look in the company, I see colleagues who are inspired by what we have achieved to date and filled with determination to be part of the next breakthrough that could change the world for patients in need. As we enter a new year, I look forward to all we will accomplish together.” 

Frank D’Amelio, who retired as chief financial officer in May 2022, noted that the company was performing better than at any other time during his almost 15-year tenure with Pfizer. At the end of 2021, Pfizer issued guidance for 2022 that represented the highest level of annual revenues and adjusted diluted earnings per share in Pfizer’s history. 

“We have prudently deployed our capital through multiple business development transactions in recent months to advance our strategies, always with an eye toward bolstering growth in the latter half of this decade and beyond,” D’Amelio stated. “I have never been more confident in the future of Pfizer.”

Although Comirnaty has been determined to be very effective in protecting patients from COVID-19, the Omicron subvariants have been able to slip past the initial versions of the vaccine. Bourla in late September 2022 announced that he had gotten COVID again. 

“I wanted to let you know that I have tested positive for COVID,” he stated. “I’m feeling well and symptom free. I’ve not had the new bivalent booster yet, as I was following CDC guidelines to wait three months since my previous COVID case which was back in mid-August. While we’ve made great progress, the virus is still with us.”

Performance & Outlook

In 2021, Pfizer generated revenue of $81.29 billion compared with $41.65 billion in 2020. Net income for 2021 was $21.98 billion compared with $9.16 billion one year earlier, and diluted EPS were $3.85 compared with $1.63.

First-half 2022 revenues were $53.40 billion compared with $33.42 billion in the same period last year. Reported net income was $17.77 billion compared with first-half 2021’s $10.44 billion. Adjusted dilute earnings per share were $3.66 versus $2.01.

In discussing second-quarter 2022 results, David Denton, Pfizer’s new chief financial officer and executive VP, noted strong operational revenue and earnings growth driven by multiple therapeutic areas across the company, while the COVID-19 franchises propelled Pfizer to an all-time high in quarterly sales. 

Meanwhile, the company continues to prioritize high-value uses for its capital, with an emphasis on reinvesting in the business by funding internally and externally developed science and innovation while also continuing to grow its dividend and buy back shares, when appropriate, to help offset dilution. 

“I am confident that Pfizer is well-positioned to continue to deliver exceptional value for our patients and shareholders going forward,” Denton stated.

For full-year 2022, Pfizer raised its guidance, expecting revenue of $98 to $102 billion and adjusted diluted earnings per share of $6.30 to $6.45.

As company executives noted, leading Pfizer’s recent stratospheric growth was Comirnaty, which was also Pfizer’s No. 1 product in 2021 sales. The vaccine generated $36.78 billion in direct sales and alliance revenues for Pfizer compared with $154 million in 2020. Last year, Pfizer managed to exceed its goal of manufacturing 3 billion doses of Comirnaty.

In the first half of 2022, Comirnaty direct sales and alliance revenues totaled $22.08 billion compared with the first-half 2021 amount of $11.30 billion. With Pfizer’s September 2022 launch of a booster aimed at the BA.4/BA.5 strain of Omicron, those numbers are expected to grow for the full year, with Pfizer anticipating $32 billion of direct sales and alliance revenues for Comirnaty.

Comirnaty has not been the only weapon in Pfizer’s COVID-19 arsenal. After Paxlovid generated $76 million in 2021, first-half 2022 sales ballooned into $9.59 billion.

These sales/revenues have been driven by the company’s various supply agreements. In November 2021, Pfizer announced an agreement with the U.S. government to supply 10 million treatment courses of Paxlovid for a total purchase price of approximately $5.3 billion. In January 2022, the U.S. government committed to purchase an additional 10 million treatment courses of Paxlovid, bringing the total number to 20 million. About 10 million Paxlovid treatment courses were expected to be delivered to the United States by the end of June 2022, with the remaining 10 million expected to follow by the end of September 2022. 

In December 2021, Pfizer announced an agreement with the United Kingdom to supply an additional 2.5 million treatment courses of Paxlovid, in addition to the 250,000 treatment courses previously contracted. A total of 2.75 million courses are expected to be delivered to the U.K. through 2022.

Also in December 2021, Pfizer announced that the company planned to manufacture up to 120 million treatment courses of Paxlovid by the end of 2022, depending on the global need, which will be driven by advance purchase agreements, with 30 million courses expected to be produced in the first half of 2022 and the remaining 90 million courses expected to be produced in second-half 2022.

In June 2022, Pfizer and BioNTech announced a new vaccine supply agreement with the U.S. government to provide an additional 105 million COVID-19 doses including adult Omicron-adapted COVID-19 vaccines. The U.S. government will pay the companies $3.2 billion upon delivery of the first 105 million doses, and has the option to purchase up to 195 million additional doses, bringing the total number of potential doses to 300 million. 

As of July, Pfizer anticipated full-year 2022 Comirnaty direct sales and alliance revenues of about $32 billion and Paxlovid revenue of about $22 billion.

Pfizer is also providing its COVID-19 products to low-income countries through various mechanisms. In September 2022, Pfizer signed an agreement to supply up to 6 million treatment courses of Paxlovid to the Global Fund as part of its COVID-19 Response Mechanism (C19RM). The C19RM has been the primary channel for providing grant support to low- and middle-income countries to purchase COVID-19 tests, treatments, personal protective equipment and critical elements of health systems strengthening. Paxlovid treatment courses will be available for procurement through this mechanism, subject to local regulatory approval or authorization, by the 132 grant-eligible countries determined by the Global Fund based on income classification and disease burden.

Pfizer expected supply to be available starting in 2022, pending regulatory authorization or approval and based on country demand. Through the Global Fund’s framework and mechanism, eligible countries will be offered treatment courses according to Pfizer’s tiered pricing approach, where all low- and lower-middle-income countries will pay a not-for-profit price, while upper-middle-income countries will pay the price defined in Pfizer’s tiered pricing approach. Additional contractual details of the agreement were not disclosed.

“After so much disruption and loss due to COVID-19, we must continue to accelerate access to Paxlovid as a treatment option for high-risk patients in all regions of the world along with test and treat programs that help get treatment quickly to those in need,” Bourla stated. “This agreement with the Global Fund is a critical step that will boost equitable access for high-risk patients in low- and
middle-income countries.”

The Global Fund agreement, along with a pact signed with UNICEF for the supply of up to 4 million treatment courses for low- and middle-income countries earlier this year, is part of Pfizer’s comprehensive global strategy for equitable supply of and access to Paxlovid. This includes a voluntary licensing agreement with Medicines Patent Pool (MPP) to enable the development and distribution of generic versions of Pfizer’s oral treatment to further expand long-term global supply and access. 

MPP has signed sublicense agreements with 38 manufacturers, who will supply the generic versions in 95 low- and lower-middle-income countries. Courses produced by these manufacturers were expected to be available as early as the fourth quarter of 2022.

Pfizer will also provide product donation and funding to the COVID Treatment Quick Start Consortium to support efforts to accelerate COVID-19 testing and improve access to treatments in under-resourced parts of the world.

Additionally, Pfizer is looking to increase the supply of Paxlovid through An Accord for a Healthier World, a first-of-its-kind initiative to enable sustained, equitable access to high-quality medicines and vaccines for 1.2 billion people living in lower-income countries launched in May 2022. 

Through the Accord, Pfizer has committed to provide its patent-protected medicines and vaccines available in the U.S. or European Union, including Paxlovid, on a not-for-profit basis to 45 lower-income countries and will collaborate with government and global health leaders to address barriers that limit access beyond supply, like diagnosis, education, infrastructure, storage and more.

Pfizer’s anticoagulant Eliquis generated alliance revenues and direct sales of $5.97 billion in 2021, 20.6 percent more than in 2020. The first-half 2022 total reached $3.54 billion, up 13 percent versus first-half 2021. 

Ibrance, which is for the treatment of HR-positive and HER2-negative breast cancer, reached sales of $5.44 billion in 2021, about $45 million more than in 2020. First-half 2022 sales were $2.56 billion, 4 percent less than in the same period last year. 

For the Prevnar family of pneumococcal vaccines, Pfizer recorded 2021 sales of $5.27 billion, 10 percent less than in 2020. First-half 2022 sales were $2.99 billion, 19 percent more than in the first half of 2021.

The rheumatoid arthritis, psoriatic arthritis and ulcerative colitis treatment Xeljanz produced 2021 sales of $2.46 billion, about 1 percent more than in 2020. In the first six months of 2022, sales were $802 million, a decrease of 29 percent compared with first-half 2021. Company executives say the decrease was driven primarily by declines in net price due to unfavorable changes in channel mix, decreased prescription volumes resulting from ongoing shifts in prescribing patterns related to Janus kinase (JAK) class label changes, and unfavorable wholesaler inventory buying patterns.

Pfizer’s Vyndaqel/Vyndamax for treating transthyretin amyloid cardiomyopathy (ATTR-CM) generated 2021 sales of $2.02 billion, 56 percent more than in the previous year. First-half 2022 sales were $1.16 billion, 22 percent more than in first-half 2021. The increase was attributed to continued strong uptake of the transthyretin amyloid cardiomyopathy indication, primarily in the United States and developed Europe, but was partially offset by a planned price decrease that went into effect in Japan.

The rheumatoid arthritis drug Enbrel recorded 2021 sales of $1.19 billion, 12 percent less than in 2020. Sales in the first half of 2022 were $537 million, 11 percent less than in the first half 0f last year. Both full-year 2021 and half-year 2022 sales for the drug, which Pfizer markets outside the United States and Canada, was from biosimilar competition. 

The prostate cancer treatment Xtandi posted 2021 alliance revenue of $1.19 billion, 16 percent more than in the previous year. Alliance revenue in the first six months of 2022 was $558 million, 2 percent less than in the same period of 2021. 

The kidney cancer drug Inlyta’s 2021 sales increased to slightly more than $1 billion from $787 million in 2020. Sales in the first half of this year were also higher than in the same period of 2021, at $508 million compared with $486 million.

Sulperazon 2021 sales amounted to $683 million compared with $618 million during the previous year. The broad-spectrum antibiotic experienced 26 percent growth in the first half of 2022 compared with the same period last year, totaling $420 million.

Sales of the cancer drug Sutent were $673 million in 2021 compared with $819 million in 2020. Sales continued to decrease in first-half 2022, at $211 million, 46 percent less than in same period last year. The decreases primarily reflect lower volume demand following the loss of U.S. patent exclusivity in August 2021 and in Europe during January 2022.

Pfizer’s biosimilar to Remicade, Inflectra/Remsima, posted 2021 sales of $657 million, $2 million less than the previous year’s total. Sales in the first half of 2022 were $272 million, 13 percent less than in first-half 2021.

The Premarin family of hormone replacement therapies generated $563 million in 2021 compared with $680 million in 2020. First-half 2022 sales were 20 percent less than in first-half 2021, at $217 million.

The chronic myelogenous leukemia drug Bosulif had sales of $540 million, 20 percent more than in 2020. Sales in the first half of 2022 were $284 million, 10 percent more than in the same period last year.

More acquisitions, partnerships

Pfizer continued to make acquisitions and engage in partnerships during 2021 and 2022.

In August 2022, Pfizer announced that it was acquiring Global Blood Therapeutics Inc. GBT is a biopharmaceutical company dedicated to the discovery, development, and delivery of life-changing treatments that provide hope to underserved patient communities, starting with sickle cell disease (SCD). 

Management says the acquisition complements and further enhances Pfizer’s more than 30-year heritage in rare hematology and reinforces the company’s commitment to SCD by bringing expertise and a leading portfolio and pipeline with the potential to address the full spectrum of critical needs in this underserved community. Pfizer intends to continue to build on the companies’ shared commitment to and engagement with the SCD community.

Under the terms of the transaction, Pfizer will acquire all the outstanding shares of GBT for $68.50 per share in cash, for a total enterprise value of approximately $5.4 billion, including debt and net of cash acquired. The boards of directors of both companies have unanimously approved the transaction.

GBT developed Oxbryta (voxelotor) tablets, a first-in-class medicine that directly targets the root cause of SCD. Oxbryta was approved in the United States in November 2019 and is also approved in the European Union, United Arab Emirates, Oman, and Great Britain. Net sales for Oxbryta were about $195 million in 2021. Leveraging its global platform, Pfizer plans to accelerate distribution of GBT’s innovative treatment to parts of the world most impacted by SCD.

In addition, GBT is developing GBT021601 (GBT601), an oral, once-daily, next-generation sickle hemoglobin (HbS) polymerization inhibitor in the Phase II portion of a Phase II/III clinical study. GBT601 has the potential to be a best-in-class agent targeting improvement in both hemolysis and frequency of vaso-occlusive crisis (VOC). GBT’s pipeline also includes inclacumab, a fully human monoclonal antibody targeting P-selectin which is being evaluated in two Phase III clinical trials as a potential quarterly treatment to reduce the frequency of VOCs and to reduce hospital readmission rates due to VOCs. 

GBT601 and inclacumab have received Orphan Drug and Rare Pediatric Disease designations from the FDA. If approved, GBT’s pipeline and Oxbryta have the potential for an SCD franchise that could achieve combined worldwide peak sales of more than $3 billion.

“The deep market knowledge and scientific and clinical capabilities we have built over three decades in rare hematology will enable us to accelerate innovation for the sickle cell disease community and bring these treatments to patients as quickly as possible,” Bourla stated.

In May 2022, Pfizer said it would be acquiring Biohaven Pharmaceutical Holding Company Ltd. Biohaven is the maker of Nurtec ODT, an innovative dual-acting migraine therapy approved for both acute treatment and episodic prevention of migraine in adults.

Under the terms of the agreement, Pfizer will acquire all outstanding shares of Biohaven not already owned by Pfizer for $148.50 per share in cash. Biohaven common shareholders, including Pfizer, will also receive 0.5 of a share of New Biohaven, a new publicly traded company that will retain Biohaven’s non-CGRP development stage pipeline compounds, per Biohaven common share. The boards of directors of both Biohaven and Pfizer have unanimously approved the transaction. Pfizer will pay transaction consideration totaling about $11.6 billion in cash. Pfizer will also make payments at closing to settle Biohaven’s third-party debt and for the redemption of all outstanding shares of Biohaven’s redeemable preferred stock. The $148.50 cash consideration represents a premium of about 33 percent to Biohaven’s volume weighted average selling price of $111.70 over the three months prior to the announcement of the transaction.

The proposed transaction includes the acquisition of Biohaven’s calcitonin gene-related peptide (CGRP) programs including Nurtec ODT, zavegepant, and a portfolio of five pre-clinical CGRP assets.

Nurtec ODT is also approved in the European Union under the trade name Vydura, for both acute treatment of migraine and prophylaxis of episodic migraine. Zavegepant nasal spray’s New Drug Application (NDA) was accepted during May 2022 in the United States as an intranasal spray for the acute treatment of migraine. Zavegepant is also in clinical development as an oral soft gel for chronic migraine prevention. 

“Today’s announcement builds on our legacy of delivering breakthroughs for patients living with complex pain disorders and diseases that disproportionately impact women,” said Nick Lagunowich, global president, Pfizer Internal Medicine. “Nurtec ODT, which is already the No. 1 prescribed migraine medicine in its class in the United States, coupled with Biohaven’s CGRP pipeline, offers hope for patients suffering from migraine worldwide. We believe Pfizer is uniquely positioned to help the portfolio reach its full potential given our leading scale and capabilities, including comprehensive field force engagement with primary care physicians, specialists and health systems delivering the right information at the right time.” This agreement follows the November 9, 2021, collaboration for the commercialization of rimegepant and zavegepant outside the United States, in connection with which Pfizer invested $350 million to acquire 2.6 percent of Biohaven’s common stock at $173 per share.

Also in August 2022, CytoReason announced an extension of its multi-year partnership with Pfizer to use the company’s artificial intelligence technology for Pfizer’s drug development programs.

Under the terms of the agreement, Pfizer will make a $20 million equity investment, have options to license CytoReason’s platform and disease models, and fund supplementary project support, in a deal potentially worth up to $110 million over the next five years.

Since launching the collaboration in 2019, Pfizer has used CytoReason’s biological models in its research to enhance the understanding of the immune system, as it develops innovative drugs for immune-mediated and immuno-oncology diseases. Company executives say CytoReason’s platform has provided Pfizer with multiple insights in R&D programs across over 20 diseases.

In June 2022, Roivant Sciences and Pfizer announced the unveiling of Priovant Therapeutics, dedicated to developing and commercializing novel therapies for autoimmune diseases with the greatest morbidity and mortality. Priovant was established in September 2021 through a transaction between Roivant and Pfizer, in which Pfizer licensed oral and topical brepocitinib’s global development rights and U.S. and Japan commercial rights to Priovant. Pfizer holds a 25 percent equity ownership interest in Priovant.

Brepocitinib is a potential first-in-class dual inhibitor of TYK2 and JAK1, a novel mechanism of action expected to potentially provide greater efficacy in multiple highly inflammatory autoimmune diseases, as compared to agents that inhibit either TYK2 or JAK1 alone. Priovant is developing oral brepocitinib as a franchise across multiple orphan and specialty autoimmune diseases with few approved therapies, high morbidity and mortality, and pathobiologies for which both TYK2 and JAK1 inhibition are expected to contribute to efficacy. 

Oral brepocitinib is being evaluated in two ongoing registrational programs. Priovant initiated a single registrational Phase III study in dermatomyositis (VALOR). Data for a large, global Phase IIb study in SLE, designed to serve as one of two registrational studies, is anticipated in 2H 2023.

“Roivant has a proven track record in late-stage inflammation and immunology drug development, which is why we are confident that Priovant will successfully continue the development of much needed innovative treatments for these patients,” said Mikael Dolsten, chief scientific officer, president, worldwide research, development and medical at Pfizer. “This collaboration will enable allocation of resources to advance development of brepocitinib while allowing Pfizer to focus on diversifying its pipeline so that patients may benefit from potential options against inflammatory diseases.”

Oral brepocitinib has been evaluated in 14 Phase I and Phase II studies, including five placebo-controlled Phase II studies in psoriatic arthritis, plaque psoriasis, ulcerative colitis, alopecia areata, and hidradenitis suppurativa. All of these studies generated statistically significant and clinically meaningful results. Oral brepocitinib’s safety database includes over 1,000 exposed subjects and suggests a safety profile similar to those of approved JAK inhibitors. Priovant initiated a single registrational Phase III study evaluating oral brepocitinib in dermatomyositis (VALOR). 

In addition to brepocitinib, Pfizer has licensed ropsacitinib, a selective TYK2 inhibitor, to Priovant.

Also in June 2022, Pfizer successfully completed its acquisition of ReViral, a privately held, clinical-stage biopharmaceutical company focused on discovering, developing and commercializing novel antiviral therapeutics that target respiratory syncytial virus (RSV). 

Under the terms of the agreement, Pfizer acquired ReViral for a total consideration of up to $525 million, including upfront and development milestones. 

ReViral brings to Pfizer a portfolio of promising therapeutic candidates, including sisunatovir, an orally administered inhibitor designed to block fusion of the RSV virus to the host cell. Sisunatovir has been granted Fast Track designation by the FDA. Sisunatovir significantly reduced viral load in a Phase II RSV human challenge study in healthy adults and is in Phase II clinical development in infants. The development program for sisunatovir is expected to continue in both adult and pediatric populations. A second program is focused on the inhibition of RSV replication targeting the viral N protein. The lead candidate in this program is in Phase II clinical development.

“This acquisition further demonstrates our commitment to advancing pioneering science – both through our in-house expertise and our work with leading, innovative companies – with the goal of delivering new breakthroughs to patients suffering from serious infectious diseases,” Dr. Dolsten said. “We believe these therapeutic candidates – and the scientific expertise that has advanced their development – will complement our ongoing work to help combat RSV infections, and we look forward to welcoming our new colleagues to further support these endeavors.”

If successful, Pfizer believes annual revenue for these programs has the potential to reach or exceed $1.5 billion.

As of March 2022, Pfizer completed its acquisition of Arena Pharmaceuticals, a clinical-stage company developing innovative potential therapies for the treatment of several immuno-inflammatory diseases.

Management says Arena Pharmaceuticals brings to Pfizer a portfolio of diverse and promising development-stage therapeutic candidates in gastroenterology, dermatology, and cardiology, including etrasimod, an oral, selective sphingosine 1-phosphate (S1P) receptor modulator in development for a range of immuno-inflammatory diseases including ulcerative colitis, Crohn’s Disease, atopic dermatitis, eosinophilic esophagitis, and alopecia areata.

“We are excited to add the impressive experience and pipeline of Arena Pharmaceuticals to Pfizer’s Inflammation and Immunology therapeutic area, helping us further our purpose of developing breakthroughs to change the lives of those with immuno-inflammatory diseases,” said Mike Gladstone, global president and general manager, Pfizer inflammation and immunology. “In particular, we’re hopeful that we can accelerate clinical development of etrasimod successfully to have a positive impact on those living with these debilitating diseases.”

Arena’s pipeline includes two development-stage cardiovascular assets: temanogrel for microvascular obstruction and Raynaud’s phenomenon secondary to systemic sclerosis, and APD418 for acute heart failure.

Pipeline development

Headlines about the clinical progress of Comirnaty and Paxlovid dominated 2021 and into 2022, but Pfizer’s highlights include other development achievements as well.

Late in September 2022, Pfizer and BioNTech completed a submission to the FDA requesting Emergency Use Authorization (EUA) of a 10-µg booster dose of the companies’ Omicron BA.4/BA.5-adapted bivalent COVID-19 vaccine for children ages 5 through 11 years of age. Management says the EUA request for this age group is supported by safety and immunogenicity data from the companies’ bivalent Omicron BA.1-adapted vaccine, non-clinical and manufacturing data from the companies’ 10-µg bivalent Omicron BA.4/BA.5-adapted vaccine, and pre-clinical data from the companies’ Omicron BA.4/BA.5-adapted vaccine. An application to extend the Omicron BA.4/BA.5-adapted bivalent vaccine marketing authorization to include children ages 5 through 11 years was expected be submitted to the European Medicines Agency (EMA) soon thereafter.

The companies also initiated a Phase I/II/III study to evaluate the safety, tolerability, and immunogenicity of different doses and dosing regimens of the companies’ Omicron BA.4/BA.5-adapted bivalent COVID-19 vaccine in children 6 months through 11 years of age. 

The Phase I/II/III pediatric clinical study will have four substudies examining different bivalent vaccine dosing regimens, dose levels, and ages. Substudy A, for ages 6 through 23 months who are COVID-19 vaccine-naïve, is a Phase I dose-finding study that will evaluate 3-µg, 6-µg, and 10-µg dose levels of the bivalent vaccine. Based on Phase I, participants in the Phase II/III study will receive the selected dose as a three-dose primary series, followed by a booster dose.

Substudy B is for ages 6 months through 4 years who had previously received two to three doses of the original COVID-19 vaccine). Those who have received two doses prior to enrollment will receive both a third and fourth 3-µg dose of the bivalent vaccine. Those who have previously received three doses of the original vaccine will receive a 3-µg booster (fourth) dose of the bivalent vaccine.

Substudy C for ages 6 months through 4 years who had previously received three doses of original COVID-19 vaccine is a Phase 1 dose-finding study that will evaluate 6-µg and 10-µg dose levels of the bivalent vaccine for a fourth dose. Based on Phase I, Phase II/III will receive the selected dose as a fourth dose.

Substudy D for ages 5 through 11 years who had previously received two to three doses of the original COVID-19 vaccine will receive the bivalent vaccine as either a third or fourth 10-µg booster dose.

Pfizer and BioNTech in September announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommended converting the conditional Marketing Authorization (cMA) for Comirnaty to standard Marketing Authorization (MA) for all authorized indications and formulations. The European Commission (EC) will review the CHMP recommendation and was expected to make a final decision soon. 

The recommendation to convert the cMA to full MA is based on the totality of available efficacy and safety data provided by Pfizer and BioNTech, which confirm the benefits of the vaccine continue to outweigh its potential risks. The conversion, if approved by the EC, applies to all existing Comirnaty indications and formulations authorized in the EU, including Pfizer and BioNTech’s bivalent vaccines (Comirnaty Original/Omicron BA.1 and Comirnaty Original/Omicron BA.4-5) as booster doses for individuals aged 12 and older in the EU. 

In a separate action, the CHMP also recommended approval for Comirnaty as a 10-µg booster (third) dose given at least six months after completion of a primary series for children 5 through 11 years of age. Comirnaty 10-µg was authorized in the EU in November 2021 as a two-dose primary series for children 5 through 11 years of age. 

In June 2022, Pfizer submitted a New Drug Application (NDA) to the FDA for approval of Paxlovid for patients who are at high risk for progression to severe illness from COVID-19. Paxlovid is authorized for emergency use for the treatment of mild-to-moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing at least 40 kg [88 lbs]) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death. The submission provides the longer term follow-up data necessary for acceptance and potential approval.

“As the COVID-19 pandemic continues to evolve and be highly unpredictable, we must remain vigilant in protecting those who are at greatest risk of getting very sick from COVID-19, as they remain vulnerable to potential hospitalization or even death,” Bourla stated. “Data from our clinical development program, coupled with the more than 1.7 million patients around the world who have been prescribed our oral treatment to date, reinforce Paxlovid as an important treatment option for mild-to-moderate COVID-19 in patients at greater risk of progression to severe symptoms, regardless of vaccination status. We look forward to working with the FDA toward full regulatory approval for Paxlovid.” 

Also in September 2022, Pfizer and Sangamo Therapeutics announced that the Phase III AFFINE study evaluating giroctocogene fitelparvovec, an investigational gene therapy for patients with moderately severe to severe hemophilia A, had reopened recruitment. Trial sites were to begin to resume enrollment, with dosing expected to resume in October. All trial sites are anticipated to be active by the end of 2022 and a pivotal readout is expected in the first half of 2024.

The FDA granted Orphan Drug, Fast Track, and regenerative medicine advanced therapy (RMAT) designations to giroctocogene fitelparvovec, which also received Orphan Medicinal Product designation from the European Medicines Agency. 

Giroctocogene fitelparvovec is being developed as part of a collaboration agreement for the global development and commercialization of gene therapies for hemophilia A between Sangamo and Pfizer. In late 2019, Sangamo transferred the manufacturing technology and the Investigational New Drug (IND) application to Pfizer.

The Phase III AFFINE (NCT04370054) study is an open-label, multicenter, single arm study to evaluate the efficacy and safety of a single infusion of giroctocogene fitelparvovec in more than 60 adult (ages 18-64 years) male participants with moderately severe to severe hemophilia A. The primary endpoint is impact on annualized bleeding rate (ABR) through 15 months following treatment with giroctocogene fitelparvovec. 

This will be compared to ABR on prior FVIII prophylaxis replacement therapy. The secondary endpoints include FVIII activity level after the onset of steady state and through 15 months following infusion of giroctocogene fitelparvovec.

The FDA in August 2022 authorized a 30-µg booster dose of the Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original [15 µg] and Omicron BA.4/BA.5 [15 µg]) for individuals ages 12 years and older. An application for an Omicron-adapted bivalent vaccine for children 5 through 11 years of age was planned for submission to the FDA in early October.

“As we head into the fall and winter season, with the potential for greater SARS-CoV-2 spread in schools and at work, it is important to stay up to date with vaccines as a first line of defense against COVID-19 illness,” Bourla said.

Pfizer wants to use its mRNA technology for other disease areas. The company announced in September that the first participants have been dosed in a pivotal Phase III clinical trial to evaluate the efficacy, safety, tolerability, and immunogenicity a quadrivalent mRNA influenza vaccine candidate in about 25,000 healthy U.S. adults.

“For years, there has been a need to better address the burden of influenza, despite the use of existing seasonal flu vaccines,” said Annaliesa Anderson, Ph.D., senior VP and chief scientific officer, vaccine R&D. “Our experience with RNA viruses and mRNA technology has given us an even deeper understanding of the opportunity to potentially provide more efficacious vaccines that could further reduce the yearly rates of the severe outcomes of viral disease like flu, including hospitalization and death.

The quadrivalent modRNA vaccine candidate will encode World Health Organization recommended strains for the Northern Hemisphere 2022-23 cell culture- or recombinant-based influenza vaccines.

In August 2022, Pfizer and development partner Myovant Sciences received FDA approval of Myfembree (relugolix 40 mg, estradiol 1 mg, and norethindrone acetate 0.5 mg) as a one-pill, once-a-day therapy for the management of moderate-to-severe pain associated with endometriosis in pre-menopausal women, with a treatment duration of up to 24 months. Myfembree also is approved for heavy menstrual bleeding associated with uterine fibroids in pre-menopausal women. Myovant and Pfizer will continue to jointly commercialize Myfembree in the United States.

“This approval is an important milestone reflecting Pfizer and Myovant’s commitment to women’s health in areas of significant unmet need,” said James Rusnak, M.D., Ph.D., senior VP, chief development officer, internal medicine and hospital, global product development at Pfizer. “We look forward to making Myfembree available to women with endometriosis and broadening their options in managing this complex disorder.” 

Also in August, Pfizer and development partner Valneva SE initiated a Phase III clinical study, Vaccine Against Lyme for Outdoor Recreationists (VALOR). to investigate the efficacy, safety and immunogenicity of their investigational Lyme disease vaccine candidate, VLA15.

The randomized, placebo-controlled study will enroll approximately 6,000 participants 5 years of age and older. The study is being conducted at up to 50 sites located in areas where Lyme disease is highly endemic, including Finland, Germany, the Netherlands, Poland, Sweden, and the United States. Participants will receive three doses of VLA15 180 µg or saline placebo as a primary vaccination series followed by one booster dose of VLA15 or saline placebo (1:1 ratio).

Data from the Phase II studies continue to demonstrate strong immunogenicity in adults as well as in children, with acceptable safety and tolerability profiles in both study populations. Pending successful completion of the Phase III study, Pfizer could potentially submit a Biologics License Application (BLA) to the FDA and Marketing Authorization Application (MAA) to the EMA in 2025.

In May 2022, the FDA granted Fast Track designation to Pfizer’s investigational combination therapy for the treatment of non-alcoholic steatohepatitis (NASH) with liver fibrosis: ervogastat (PF-06865571, a diacylglycerol O-acyltransferase 2 inhibitor, or DGAT2i) and clesacostat (PF-05221304, an acetyl-CoA carboxylase inhibitor, or ACCi). 

The decision is informed by the results of Pfizer’s nonclinical studies and a Phase IIa clinical study of ervogastat/clesacostat, which showed that treatment with ervogastat/clesacostat reduced liver fat with a favorable safety and tolerability profile. These data were recently published in Nature Medicine.

“Receiving Fast Track designation from the FDA reinforces Pfizer’s belief in ervogastat/clesacostat as a potential treatment for NASH, a serious, progressive liver disease with no currently approved therapies,” said Rusnak. “We are proud to be advancing this investigational combination as part of our goal to develop innovative medicines to address some of the world’s most widespread health challenges that affect millions of people – including diseases like NASH.”

Pfizer is studying ervogastat/clesacostat in a Phase II clinical trial evaluating the impact of treatment on resolution of NASH or improvement in liver fibrosis (NCT04321031), expected to be completed in 2024. The results of this study, which also includes arms investigating ervogastat as monotherapy, will inform a potential Phase III development program.

In April 2022, Pfizer announced plans to open the first U.S. sites in the Phase III study evaluating the investigational mini-dystrophin gene therapy, fordadistrogene movaparvovec, in ambulatory patients with Duchenne muscular dystrophy (DMD). This announcement followed a notification from the FDA that the agency  lifted its clinical hold on the IND application for fordadistrogene movaparvovec and that Pfizer has addressed the agency’s requests related to the potency assay. 

The global Phase III study, CIFFREO, has been conducted in 11 countries and was paused in December 2021 to implement a protocol amendment following a fatal serious adverse event that occurred in a Phase Ib study in the non-ambulatory cohort. To date, regulatory authorities in the United Kingdom, Canada, Taiwan, Spain, and Belgium have approved the restart of the Phase III study and additional global reviews are under way. Pending regulatory feedback, Pfizer anticipated that nearly all CIFFREO sites would open by the end of June 2022.

In December 2021, a fatal serious adverse event occurred in a non-ambulatory participant in the Phase Ib study of fordadistrogene movaparvovec. Like many non-ambulatory DMD patients, the participant had more advanced disease with underlying cardiac dysfunction. Pfizer immediately paused screening, randomization, and dosing in all studies of fordadistrogene movaparvovec as the independent external data monitoring committee (eDMC) reviewed the data, and the FDA subsequently placed the IND on clinical hold. 

In February 2022, the EMA approved the company’s 20-valent pneumococcal conjugate vaccine (PCV20), which is marketed in the EU under the brand name Apexxnar. The vaccine is approved for active immunization for the prevention of invasive disease and pneumonia caused by Streptococcus pneumoniae in individuals 18 years of age and older.

“The EMA’s authorization of Apexxnar for adults continues Pfizer’s ongoing commitment to help prevent certain potentially-serious infectious respiratory diseases, including invasive pneumococcal disease and pneumonia,” said Nanette Cocero, Ph.D., global president of Pfizer Vaccines. “Apexxnar helps protect against the 20 serotypes in the vaccine, and today’s approval offers adults – through a single dose – the broadest serotype protection of any available pneumococcal conjugate vaccine in Europe.”

The authorization follows the positive opinion from the EMA’s Committee for Medicinal Products for Human Use (CHMP) announced on December 17, 2021. The authorization is valid in all 27 EU member states plus Iceland, Lichtenstein, and Norway. The EMA had accepted review of Pfizer’s MAA for the 20-valent pneumococcal conjugate vaccine candidate in February 2021.

In January 2022, the European Commission granted marketing authorization for Lorviqua (lorlatinib) as monotherapy for the treatment of adult patients with anaplastic lymphoma kinase (ALK)- positive advanced non-small cell lung cancer (NSCLC) previously not treated with an ALK inhibitor.

“For more than a decade, Pfizer has worked tirelessly in its pursuit to help transform the trajectory for people living with advanced, biomarker-driven lung cancers,” said Andy Schmeltz, global president and general manager, Pfizer Oncology. “The European Commission’s approval of Lorviqua as a first-line therapy is a significant milestone that we hope will help bring a needed and meaningful difference to those impacted by this deadly disease in Europe.”

Lorlatinib is available in the United States under the brand name Lorbrena. The approval for the first-line use of Lorviqua was based on the results of the pivotal Phase III CROWN trial, in which Lorviqua reduced the risk of disease progression or death by 72 percent compared to Xalkori (crizotinib). Additionally, in patients with measurable brain metastases, 82 percent of patients in the Lorviqua arm experienced an intracranial response (71 percent had an intracranial complete response), compared to 23 percent of Xalkori patients.