Voxelotor

iStock/ francescoch While sparking excitement among biopharma companies focused on rare and ultrarare indications, experts say FDA Commissioner Marty Makary’s proposal is light on details and raises potential concerns about safety, access and liability. While the FDA under HHS Secretary Robert F. Kennedy Jr. might seem to be worlds different than the FDA of 2024, the agency still seems to be prioritizing expediting treatments for rare diseases, particularly ultrarare conditions. As head of the FDA’s Center for Biologics Evaluation and Research (CBER) until his abrupt resignation at the end of March, Peter Marks was a passionate advocate for regulatory flexibility for rare disease therapies. In fact, Marks came under fire for his June 2024 decision to grant full approval to Sarepta Therapeutics’ Duchenne muscular dystrophy gene therapy Elevidys, overriding the recommendation of FDA advisors. Now, it appears that newly minted FDA commissioner Marty Makary wants to take up the baton. In an interview last month with former Fox News journalist Megyn Kelly, Makary unveiled plans for a new regulatory pathway for rare disease drugs, allowing for their conditional approval based on a “scientifically plausible mechanism.” The proposed pathway—about which Makary has yet to provide further details—could enable conditional approval for drugs targeting rare diseases without data from a randomized, controlled clinical trial. Patients would then be followed under a surveillance system to allow the FDA to draw conclusions as soon as meaningful data emerge, according to a Department of Health and Human Services spokesperson. It could be a boon for patients and biopharma companies, potentially removing some of the barriers to innovation that exist for rare disease drug development, including trial recruitment difficulties and low return-on-investment owing to sometimes minuscule patient populations . It could also breathe new life into the cell and gene therapy space —whose focus largely falls on these rare targets. “You can’t expect the companies to do a randomized, controlled trial; you’ll kill innovation. You’ll kill investment in those innovative ideas,” Makary said during the interview with Kelly. Marks, too, has spoken out in favor of alternative clinical trial designs, including single-arm trials, for certain gene therapies for rare diseases. “There are many rare diseases affecting dozens to a few hundred individuals in the United States where the concept of trying to do a randomized trial is very challenging at best and impossible at worst,” he told BioSpace last year. But is such a conditional approval pathway feasible? According to experts who spoke with BioSpace , maybe—but there are a number of challenges to overcome, including legal concerns over safety and the question of whether insurers would reimburse for therapies in the absence of strong clinical data of efficacy. There could also be dissent from the new CBER head, Vinay Prasad, who has voiced concern over the FDA’s current accelerated approval process, particularly in terms of confirmatory trial delays and efficacy. “It’s a little bit sketchy at this point in terms of knowing exactly what it’s going to look like,” Daniel Kracov, partner and chair of the Global Life Sciences Industry Practice at Arnold & Porter, told BioSpace of the proposal. Kracov added that the FDA cannot enact this pathway alone. “At the end of the day, this would require legislation,” he said. “I don’t think FDA can simply do this.” In an email to BioSpace , an HHS spokesperson declined to elaborate on Makary’s comments. Potential Challenges Kracov has a long history in the rare disease space. He has worked on issues related to the Orphan Drug Act, which was originally passed in 1983 to incentivize the development of drugs for rare diseases. The idea for a conditional pathway for rare disease drugs is not new, he said, noting that former acting FDA Commissioner Janet Woodcock has also advocated for such an initiative. In 2016, Woodcock overruled FDA staff in her 2016 approval of Sarepta’s Exondys 51 for DMD—a company and a rare disease that have become synonymous with this movement. At a 2024 workshop intended to address barriers to ultrarare therapy development, Woodcock noted a “mismatch” between current FDA approval standards and the realities of drug development for ultrarare diseases. “We’ve had accelerated approval. We’ve had regulatory flexibility. We’ve had one trial and confirmatory evidence. But basically, at the end of the day, the evidentiary standard is supposed to be that standard of adequate and well-controlled trials,” she said, according to BioCentury . [Approving drugs based on a plausible mechanism] is about as low a standard as you could possibly get. —Daniel Kracov, Arnold & Porter Woodcock asserted that regulatory flexibility isn’t a “viable policy” and prevailed on Congress to create a new approval pathway for therapies that can’t meet existing approval standards due to small patient populations or lack of predictive biomarkers. “What we’ve seen is a lot of cognitive dissonance internally, of people being asked on one hand to enforce the standards and on the other hand to be flexible. You can be flexible, flexible, flexible, and then pretty soon you’re going to break,” she said. Kracov agreed that to “lower the bar” and grant access to a rare disease drug may be positive but added that “there has to be a meaningful standard for the approval of products in order for payers to be willing to pay for those products.” Approving drugs based on a plausible mechanism is “about as low a standard as you could possibly get.” Kracov said that his firm, which helps biopharma companies negotiate challenges relating to drug development, approval and marketing of products, has had difficulty convincing payers to pay for products that have been approved under the FDA’s accelerated approval pathway, “much less having a conditional approval.” This is particularly true, he said, as some of these drugs may cost $1 million or more. Both Kracov and Eva Temkin, also a partner at Arnold & Porter, likened the pathway Makary is proposing to the Right to Try law, which was signed in 2018 by President Donald Trump and gives terminally ill patients the right to try experimental treatments not approved by the FDA. “If anything, it may be less protective of patients than the existing Right to Try mechanism,” Temkin, who previously served as acting deputy director for policy staff at the FDA’s Office of Therapeutic Biologics and Biosimilars, told BioSpace . The Right to Try pathway requires the drug in question to have completed Phase I safety trials and be under active investigation in clinical trials, she explained. Eligibility is also quite limited, with the pathway only being open to patients with life-threatening diseases who have exhausted approved treatment options and are unable to participate in a clinical trial for the drug. The newly proposed pathway could also present challenges in terms of assessing safety, Temkin added. “It’s very hard to imagine how adverse events could be analyzed, separated into trends. Separating the signal from the noise when you don’t even know very much about the safety or effectiveness of the drug becomes very difficult.” However, Rob Etherington, CEO of Clene, noted that modern surveillance capabilities have evolved significantly. “With the integration of electronic health records, digital biomarkers and AI-driven analytics, postmarket surveillance is now far more sophisticated, real-time and predictive than ever before,” he told BioSpace . When paired with clear regulatory expectations and confirmatory Phase III trials, these systems “can provide early, meaningful insights while maintaining patient safety.” Another challenge could arise if, after all of the data emerge, the drug is found not to be effective. The question would then become, “How exactly you take the drug off the market if it doesn’t prove out,” Temkin said. “You’ve seen that play out in accelerated approval. I think that’s going to also be a big question if there’s a conditional approval. Does the [FDA] then have to litigate, have to convene an advisory committee?” Since its inception in 1992, nearly 300 drugs have been approved under the FDA’s accelerated approval pathway , the majority in cancer indications. Recently, however, some notable drugs that received accelerated approval—including Pfizer’s sickle cell disease therapy Oxbryta and Biogen and Eisai’s Alzheimer’s medicine Aduhelm—have been withdrawn or discontinued . Finally, Kracov said it may be difficult to get buy-in from biopharma investors. “Once you head down the road with conditional approvals, how do you provide the necessary confidence to investors that they’re going to get paid for their investment over time?” A Path Forward For all of its challenges, proposed pathways such as Makary’s provide a spark of hope for rare disease–focused companies and patients. Etherington said that for a universally fatal disease like amyotrophic lateral sclerosis—often considered a rare disease, though more prevalent than many—“this approach offers significant promise.” That’s because the FDA currently approves drugs for individual indications. “ALS and other neurodegenerative diseases often share a unifying pathogenic thread—mitochondrial dysfunction,” Etherington, whose company is developing a gold nanocrystal-based drug for ALS, told BioSpace in an email. “Yet, current FDA regulatory pathways do not readily accommodate platform therapies that target core cellular dysfunctions across multiple conditions. Commissioner Makary’s remarks suggest a willingness to move beyond rigid, disease-specific silos suggesting allowance of regulatory flexibility when robust scientific rationale and mechanistic plausibility converge.” For biotechs like Clene, a conditional approval pathway “would provide a thoughtful and much-needed opportunity,” Etherington said. According to Temkin, however, the idea that biopharma companies would be willing to provide drugs to patients under such a pathway “is a fairly significant assumption.” One issue is that there could also be liability issues for companies, Kracov noted. “Is a conditional approval preemptive of state [law]suits [based on] failure to warn about something you haven’t studied yet, fully? That’s a big unknown at this point.” Emil Kakkis, president and CEO of Ultragenyx, said that companies could operate under a conditional approval pathway for some of the rarest conditions, but agreed with Kracov that issues could arise on the reimbursement front “since this has been raised recently by payors.” For Kakkis, a whole new regulatory pathway may not be necessary in most cases. “For many rare diseases in which reasonable clinical trials are possible, I would expect that the current accelerated approval pathway using biomarker or intermediate clinical endpoints should be utilized as [a] very viable pathway and one that does not require new legislation,” he told BioSpace in an email. However, he added, “I am encouraged that Makary is being open-minded about how to manage rare disease situations where unmet needs are high and the feasibility of conducting randomized clinical trials is low.” A Divided House? The possibility also exists that not all HHS leaders would be on board. While Makary has expressed enthusiasm for a conditional approval pathway for ultrarare diseases, past comments and publications indicate that newly appointed CBER head Vinay Prasad may take a different approach. In a 2015 JAMA article , the prolific oncologist and hematologist and his coauthor Chul Kim of the National Cancer Institute pointed to a 2009 Government Accountability Office report that criticized the FDA for failing to enforce postmarketing study commitments for such medicines. And last August, Prasad penned a letter with his University of California, San Francisco, lab member Timothée Olivier, questioning the FDA’s approval of Elevidys. “Despite its high cost and potential toxicity, the clinical benefits of Elevidys remain uncertain,” the pair wrote. Following Prasad’s appointment, William Blair wrote in a note to investors: “We are surprised by the announcement, because it seems to be in stark contrast to themes and initiatives that have been laid out by Dr. Makary.” BioSpace reached out to HHS regarding this matter and received the following response from a spokesperson: “Commissioner Makary and Dr. Prasad are both committed to ensuring patient safety through the Gold Standard of Science.” Certainly, a difference of opinion doesn’t have to be a negative. “It’s more likely there will be a healthy and necessary tension rather than a conflict,” Etherington said. He added that while Prasad has voiced concerns about overreliance on unvalidated biomarkers, his emphasis has consistently been on ensuring that accelerated approvals are ultimately grounded in meaningful clinical outcomes. “If a treatment demonstrates strong safety, shows biomarker-driven promise and is backed by confirmatory Phase III trials, there appears to be ample common ground between Dr. Makary’s call for regulatory agility and Dr. Prasad’s call for evidentiary integrity.”

NEW YORK--(BUSINESS WIRE)--Pfizer Inc. (NYSE: PFE) reported financial results for the first quarter of 2025 and reaffirmed its 2025 financial guidance(1). EXECUTIVE COMMENTARY Dr. Albert Bourla, Chairman and CEO of Pfizer: “We continued to execute with focus and discipline against our strategic priorities, including strengthening our R&D organization and driving improved productivity. With the underlying strength of our business, we believe we can be agile in navigating an uncertain and volatile external environment.” David Denton, CFO and EVP of Pfizer: “Our overall solid first-quarter performance demonstrates our continued focus on commercial execution amid U.S. Medicare Part D headwinds. Our focus on operational efficiency and financial discipline is driving strong results to our bottom line. We are currently trending towards the upper end of our 2025 Adjusted diluted EPS guidance range.” OVERALL RESULTS Additional Anticipated Net Cost Savings of Approximately $1.2 Billion (4) Primarily in SI&A by End of 2027 Expanded Program to Include Anticipated R&D Re-Organization Cost Savings of Approximately $500 Million by End of 2026, with Savings to be Reinvested in the Pipeline Some amounts in this press release may not add due to rounding. All percentages have been calculated using unrounded amounts. References to operational variances pertain to period-over-period changes that exclude the impact of foreign exchange rates(5). Results for the first quarter of 2025 and 2024(6) are summarized below. ($ in millions, except per share amounts) First-Quarter 2025 2024 % Change Revenues $ 13,715 $ 14,879 (8 %) Reported(2) Net Income 2,967 3,115 (5 %) Reported(2) Diluted EPS 0.52 0.55 (5 %) Adjusted(3) Income 5,237 4,674 12 % Adjusted(3) Diluted EPS 0.92 0.82 12 % REVENUES ($ in millions) First-Quarter 2025 2024 % Change Total Oper. Global Biopharmaceuticals Business (Biopharma) $ 13,441 $ 14,604 (8 %) (6 %) Pfizer CentreOne (PC1) 257 258 — 2 % Pfizer Ignite 17 17 (3 %) (3 %) TOTAL REVENUES $ 13,715 $ 14,879 (8 %) (6 %) 2025 FINANCIAL GUIDANCE(1) Pfizer’s 2025 financial guidance(1) is presented below. Revenues $61.0 to $64.0 billion Adjusted(3) SI&A Expenses $13.3 to $14.3 billion Adjusted(3) R&D Expenses $10.7 to $11.7 billion Effective Tax Rate on Adjusted(3) Income Approximately 15.0% Adjusted(3) Diluted EPS $2.80 to $3.00 CAPITAL ALLOCATION During the first three months of 2025, Pfizer deployed its capital in a variety of ways, which primarily included: $2.2 billion invested in internal research and development projects, and Approximately $90 million invested in business development transactions. No share repurchases have been completed to date in 2025. As of April 29, 2025, Pfizer’s remaining share repurchase authorization is $3.3 billion. Current financial guidance does not anticipate any share repurchases in 2025. Pfizer has actively de-levered and as of March 30, 2025 is below our previously stated gross leverage(7) target. The company expects to continue to de-lever in a prudent manner in order to maintain a balanced capital allocation strategy. This includes maintaining the flexibility to deploy capital towards potential value-creating business development transactions and the potential to return capital to shareholders through share repurchases. Diluted weighted-average shares outstanding of 5,710 million and 5,697 million were used to calculate Reported(2) and Adjusted(3) diluted EPS for first-quarter 2025 and 2024, respectively. QUARTERLY FINANCIAL HIGHLIGHTS (First-Quarter 2025 vs. First-Quarter 2024) First-quarter 2025 revenues totaled $13.7 billion, a decrease of $1.2 billion, or 8%, compared to the prior-year quarter, reflecting an operational decrease of $908 million, or 6%, as well as an unfavorable impact of foreign exchange of $256 million, or 2%. The operational decrease was primarily driven by a decline in Paxlovid revenues, partially offset by growth from the Vyndaqel family, Comirnaty(8), and several other products across categories despite the unfavorable impact of higher manufacturer discounts resulting from the Inflation Reduction Act (IRA) Medicare Part D Redesign. First-quarter 2025 operational revenue reflected higher revenues primarily for: more than offset primarily by lower revenues for: GAAP Reported(2) Statement of Operations Highlights SELECTED REPORTED(2) COSTS AND EXPENSES ($ in millions) First-Quarter 2025 2024 % Change Total Oper. Cost of Sales(2) $ 2,845 $ 3,379 (16 %) (9 %) Percent of Revenues 20.7 % 22.7 % N/A N/A SI&A Expenses(2) 3,031 3,495 (13 %) (12 %) R&D Expenses(2) 2,203 2,493 (12 %) (11 %) Acquired IPR&D Expenses(2) 9 — * * Other (Income)/Deductions—net(2) 953 680 40 % 54 % Effective Tax Rate on Reported(2) Income (6.8 %) 8.6 % * Indicates calculation not meaningful or results are greater than 100%. First-quarter 2025 Cost of Sales(2) as a percentage of revenues decreased by 2.0 percentage points compared to the prior-year quarter, driven primarily by a favorable revision of our estimate of accrued royalties and the favorable impact of foreign exchange, partially offset by the unfavorable impact of changes in sales mix as well as the non-recurrence of the Paxlovid favorable final adjustment(9) recorded in the first quarter of 2024 to the estimated non-cash revenue reversal recorded in the fourth quarter of 2023. First-quarter 2025 SI&A Expenses(2) decreased 12% operationally compared with the prior-year quarter, primarily reflecting ongoing productivity improvements that drove a decrease in marketing and promotional spend for various products and lower spending in corporate enabling functions, as well as lower spending on COVID-19 products. First-quarter 2025 R&D Expenses(2) decreased 11% operationally compared with the prior-year quarter, driven primarily by a net decrease in spending due to pipeline focus and optimization, as well as lower compensation-related expenses. The unfavorable period-over-period change in Other (income)/deductions—net(2) of $273 million for the first quarter of 2025, compared with the prior-year quarter, was driven primarily by (i) net losses on equity securities in the first quarter of 2025 versus net gains on equity securities in the first quarter of 2024, (ii) the non-recurrence of a gain on the partial sale of our investment in Haleon plc in the first quarter of 2024 and (iii) higher intangible asset impairment charges; partially offset by (iv) lower net interest expense. Pfizer’s effective tax rate on Reported(2) income for the first quarter of 2025 is negative, primarily due to favorable global income tax resolutions in multiple tax jurisdictions spanning multiple tax years, as well as a favorable change in the jurisdictional mix of earnings. Adjusted(3) Statement of Operations Highlights SELECTED ADJUSTED(3) COSTS AND EXPENSES ($ in millions) First-Quarter 2025 2024 % Change Total Oper. Adjusted(3) Cost of Sales $ 2,593 $ 3,036 (15 %) (8 %) Percent of Revenues 18.9 % 20.4 % N/A N/A Adjusted(3) SI&A Expenses 3,010 3,454 (13 %) (12 %) Adjusted(3) R&D Expenses 2,173 2,477 (12 %) (12 %) Adjusted(3) Other (Income)/Deductions—net 246 296 (17 %) 14 % Effective Tax Rate on Adjusted(3) Income 7.8 % 16.6 % See the reconciliations of certain Reported(2) to non-GAAP Adjusted(3) financial measures and associated footnotes in the financial tables section of this press release located at the hyperlink below. RECENT NOTABLE DEVELOPMENTS (Since February 4, 2025) Product Developments Product/Project Milestone Recent Development Link Abrysvo (Respiratory Syncytial Virus Vaccine) Regulatory April 2025. Announced the European Commission (EC) amended the marketing authorization for Abrysvo to extend the indication to include prevention of lower respiratory tract disease (LRTD) caused by respiratory syncytial virus (RSV) in individuals 18 through 59 years of age. The authorization is valid in all 27 EU member states plus Iceland, Liechtenstein, and Norway. Full Release ACIP Vote April 2025. Announced the U.S. Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices (ACIP) voted to expand its recommendation for the use of RSV vaccines approved for adults 50-59 years of age at increased risk of RSV-associated LRTD, which includes Abrysvo. The updated ACIP recommendation, which lowers the recommended age for RSV vaccination from 60 to 50 for high-risk adults, is pending final approval by the director of the CDC and the Department of Health and Human Services. Full Release Adcetris (brentuximab vedotin) Regulatory February 2025. Announced the U.S. Food and Drug Administration (FDA) approved the supplemental Biologics License Application (sBLA) for Adcetris in combination with lenalidomide and a rituximab product for the treatment of adult patients with relapsed or refractory large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from indolent lymphoma, or high-grade B-cell lymphoma, after two or more lines of systemic therapy who are not eligible for autologous hematopoietic stem cell transplantation (auto-HSCT) or chimeric antigen receptor (CAR) T-cell therapy. Full Release Padcev (enfortumab vedotin-ejfv) Phase 3 Results February 2025. Pfizer and Astellas Pharma Inc. presented additional follow-up results from the Phase 3 EV-302 clinical trial (also known as KEYNOTE-A39) evaluating the efficacy and safety of Padcev plus Keytruda(10) (pembrolizumab, a PD-1 inhibitor) in patients with previously untreated locally advanced or metastatic urothelial cancer (la/mUC). The results showed a sustained overall survival (OS) and progression-free survival (PFS) benefit consistent with the findings of the primary analysis after an additional 12 months of follow-up (median follow-up of 29.1 months), with no new safety signals identified. Full Release Talzenna (talazoparib) Phase 3 Results February 2025. Announced positive OS results from the Phase 3 TALAPRO-2 study of Talzenna, an oral poly ADP-ribose polymerase (PARP) inhibitor, in combination with Xtandi (enzalutamide), an androgen receptor pathway inhibitor (ARPI), demonstrating a statistically significant and clinically meaningful improvement in OS compared to placebo plus Xtandi in patients with metastatic castration-resistant prostate cancer (mCRPC), with or without homologous recombination repair (HRR) gene mutations. The safety profile of Talzenna plus Xtandi was generally consistent with the known safety profile of each medicine. Full Release Pipeline Developments A comprehensive update of Pfizer’s development pipeline was published today and is now available at www.pfizer.com/science/drug-product-pipeline. It includes an overview of Pfizer’s research and a list of compounds in development with targeted indication and phase of development, as well as mechanism of action for some candidates in Phase 1 and all candidates from Phase 2 through registration. Product/Project Milestone Recent Development Link danuglipron Discontinued April 2025. Announced the decision to discontinue development of danuglipron (PF-06882961), an oral glucagon-like peptide-1 (GLP-1) receptor agonist, which was being investigated for chronic weight management. This decision followed a review of the totality of information, including all clinical data generated to date for danuglipron and recent input from regulators. The company remains committed to evaluating and advancing promising programs for cardiovascular and metabolic diseases, including obesity. Full Release sasanlimab Phase 3 Results April 2025. Presented results from the pivotal Phase 3 CREST trial of sasanlimab, an investigational anti-PD-1 monoclonal antibody (mAb), in combination with standard of care (SOC) Bacillus Calmette-Guérin (BCG) as induction therapy with or without maintenance in patients with BCG-naïve, high-risk non-muscle invasive bladder cancer (NMIBC). The findings showed a 32% reduction in risk of disease-related events, including high-grade disease recurrence or progression, with the sasanlimab combination regimen as compared with SOC treatment alone. The overall safety profile of sasanlimab in combination with BCG was generally consistent with the known profile of BCG and data reported from clinical trials with sasanlimab. The profile of sasanlimab was also generally consistent with the reported safety profile of PD-1 inhibitors. Pfizer has shared these data with global health authorities to support potential regulatory filings. Full Release vepdegestrant Phase 3 Results March 2025. Arvinas, Inc. and Pfizer announced topline results from the Phase 3 VERITAC-2 clinical trial (NCT05654623) evaluating vepdegestrant monotherapy versus fulvestrant in adults with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced or metastatic breast cancer whose disease progressed following prior treatment with cyclin-dependent kinase (CDK) 4/6 inhibitors and endocrine therapy. The trial met its primary endpoint in the estrogen receptor 1-mutant (ESR1m) population, demonstrating a statistically significant and clinically meaningful improvement in PFS compared to fulvestrant. The results exceeded the pre-specified target hazard ratio of 0.60 in the ESR1m population. The trial did not reach statistical significance in improvement in PFS in the intent-to-treat (ITT) population. Full Release Corporate Developments Topic Recent Development Link Cost Realignment Program(4) Announced at Q1-2025 Earnings. Pfizer announced approximately $1.2 billion of additional anticipated savings associated with its ongoing cost realignment program(4), expected to be achieved by the end of 2027, designed to further reduce costs primarily in SI&A driven in large part by enhanced digital enablement, including automation and AI, and simplification of business processes. We expect one-time costs to achieve the additional savings to be incurred through 2027 and to total approximately $1.6 billion, primarily representing cash expenditures for severance, digital enablement and implementation. We remain on track to deliver net cost savings of approximately $4.5 billion by the end of 2025, and, with the additional targeted savings, we now expect total net cost savings of approximately $5.7 billion from this program through 2027. N/A Announced at Q1-2025 Earnings. In connection with our efforts to simplify the structure and sharpen the focus of our R&D organization, in the first quarter of 2025 we expanded this program after having identified additional opportunities to drive improvements in productivity and operational efficiencies through enhanced digital enablement, including automation and AI, and simplification of business processes. Savings associated with the simplification of our R&D organization are anticipated to be realized by the end of 2026 and are expected to total approximately $500 million and be reinvested in R&D programs. We expect one-time costs to implement these initiatives to be incurred through 2026 and to total approximately $600 million, primarily representing cash expenditures for severance, digital enablement and implementation. N/A Haleon Stock Sale March 2025. Pfizer sold 618 million ordinary shares of its investment in Haleon to institutional investors and separately Haleon purchased 44 million ordinary shares from Pfizer for a combined total net proceeds of approximately $3.3 billion. This follows the previously announced sale of 700 million Haleon shares in January 2025 which resulted in approximately $3.0 billion in net cash proceeds. Pfizer has fully exited its position in Haleon. N/A R&D Leadership March 2025. James List, M.D., Ph.D., joined Pfizer as Chief Internal Medicine Officer, overseeing the company’s Internal Medicine portfolio, from early discovery to late development, inclusive of Medical Affairs and Business Development strategies. He is responsible for advancing Pfizer’s emerging pipeline of cardiovascular, metabolic, and obesity medicines. Dr. List reports to Chris Boshoff, M.D., Ph.D., Chief Scientific Officer and President, Pfizer Research & Development. Full Release February 2025. Announced Jeffrey Legos, Ph.D., MBA, will join Pfizer as Chief Oncology Officer and will be responsible for leading the company’s Oncology R&D, overseeing all functions from pre-clinical to late-stage clinical development activities. Dr. Legos will report to Chris Boshoff, and will succeed Roger Dansey, M.D., Interim Chief Oncology Officer, who will transition to retirement as previously communicated. Full Release February 2025. Announced Patrizia Cavazzoni, M.D., rejoined Pfizer as Chief Medical Officer, Executive Vice President. In this role, Dr. Cavazzoni leads Pfizer’s regulatory, pharmacovigilance, safety, epidemiology, and medical information and evidence generation, among other medical functions, and reports to Chris Boshoff. Full Release PFIZER TO HOST CONFERENCE CALL Please find Pfizer’s press release and associated financial tables, including reconciliations of certain GAAP reported to non-GAAP adjusted information, at the following hyperlink: https://investors.pfizer.com/Q1-2025-PFE-Earnings-Release (Note: If clicking on the above link does not open a new webpage, you may need to cut and paste the above URL into your browser's address bar.) Pfizer will host a live conference call and webcast today at 10:00 AM EDT. To access the live conference call and view the first-quarter 2025 earnings presentation, accompanying prepared remarks from management, and infographic, visit our website at pfizer.com/investors. You can also listen to the conference call by dialing either 800-456-4352 in the U.S. and Canada or 785-424-1086 outside of the U.S. and Canada. The passcode is “67619”. The transcript and webcast replay of the call will be made available on our website at pfizer.com/investors within 24 hours after the end of the live conference call and will be accessible for at least 90 days. For additional details, see the financial schedules and product revenue table within the press release located at the hyperlink above, and the attached disclosure notice. (1) Pfizer does not provide guidance for U.S. generally accepted accounting principles (GAAP) Reported financial measures (other than revenues) or a reconciliation of forward-looking non-GAAP financial measures to the most directly comparable GAAP Reported financial measures on a forward-looking basis because it is unable to predict with reasonable certainty the ultimate outcome of unusual gains and losses, certain acquisition-related expenses, gains and losses from equity securities, actuarial gains and losses from pension and postretirement plan remeasurements, potential future asset impairments and pending litigation without unreasonable effort. These items are uncertain, depend on various factors, and could have a material impact on GAAP Reported results for the guidance period. Financial guidance for full-year 2025 reflects the following: Does not assume the completion of any business development transactions not completed as of March 30, 2025. An anticipated unfavorable revenue impact of approximately $0.6 billion due to recent and expected generic and biosimilar competition for certain products that have recently lost patent or regulatory protection or that are anticipated to lose patent or regulatory protection. Exchange rates assumed are a blend of actual rates in effect through first-quarter 2025 and mid-April 2025 rates for the remainder of the year. Guidance for Adjusted (3) diluted EPS assumes diluted weighted-average shares outstanding of approximately 5.74 billion shares, and assumes no share repurchases in 2025. Does not currently include any potential impact related to future tariffs and trade policy changes, which we are unable to predict at this time. (2) Revenues is defined as revenues in accordance with U.S. GAAP. Reported net income and its components are defined as net income attributable to Pfizer Inc. common shareholders and its components in accordance with U.S. GAAP. Reported diluted earnings per share (EPS) is defined as diluted EPS attributable to Pfizer Inc. common shareholders in accordance with U.S. GAAP. (3) Adjusted income and Adjusted diluted EPS are defined as U.S. GAAP net income attributable to Pfizer Inc. common shareholders and U.S. GAAP diluted EPS attributable to Pfizer Inc. common shareholders before the impact of amortization of intangible assets, certain acquisition-related items, discontinued operations and certain significant items. See the accompanying reconciliations of certain GAAP Reported to Non-GAAP Adjusted information for the first quarter of 2025 and 2024 in the press release at the hyperlink above. Adjusted income and its components and Adjusted diluted EPS measures are not, and should not be viewed as, substitutes for U.S. GAAP net income and its components and diluted EPS(2). See the Non-GAAP Financial Measure: Adjusted Income section of Management’s Discussion and Analysis of Financial Condition and Results of Operations in Pfizer’s 2024 Annual Report on Form 10-K and the accompanying Non-GAAP Financial Measure: Adjusted Income section of the press release located at the hyperlink above for a definition of each component of Adjusted income as well as other relevant information. (4) Approximately $4.5 billion of overall net cost savings from Pfizer’s ongoing cost realignment program are expected to be achieved by the end of 2025. An additional approximately $1.2 billion of anticipated net cost savings is expected to be fully achieved by the end of 2027. The net cost savings are calculated versus the midpoint of Pfizer’s 2023 SI&A and R&D expense guidance provided on August 1, 2023. (5) References to operational variances in this press release pertain to period-over-period changes that exclude the impact of foreign exchange rates. Although foreign exchange rate changes are part of Pfizer’s business, they are not within Pfizer’s control and because they can mask positive or negative trends in the business, Pfizer believes presenting operational variances excluding these foreign exchange changes provides useful information to evaluate Pfizer’s results. (6) Pfizer’s fiscal year-end for international subsidiaries is November 30 while Pfizer’s fiscal year-end for U.S. subsidiaries is December 31. Therefore, Pfizer’s first quarter for U.S. subsidiaries reflects the three months ended on March 30, 2025 and March 31, 2024, while Pfizer’s first quarter for subsidiaries operating outside the U.S. reflects the three months ended on February 23, 2025 and February 25, 2024. (7) Gross leverage (Adjusted Debt to Non-GAAP Adjusted EBITDA ratio) is determined by comparing our total debt (including short-term borrowings, long-term debt, repatriation tax, and lease liabilities (short- and long-term)) as of March 30, 2025 to Non-GAAP Adjusted EBITDA. Non-GAAP Adjusted EBITDA is determined by making the following adjustments to GAAP Income from continuing operations before provision/(benefit) for taxes on income: (i) adding net interest expense, depreciation & amortization, acquisition-related charges, restructuring charges and asset impairment charges; and (ii) adjusting by actuarial valuation and other pension and postretirement plan gains/(losses), gains/(losses) on equity securities, and certain other certain significant items. (8) As used in this document, “Comirnaty” refers to, as applicable, and as authorized or approved, the Pfizer-BioNTech COVID-19 Vaccine; Comirnaty (COVID-19 Vaccine, mRNA) original monovalent formula; the Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5); the Pfizer-BioNTech COVID-19 Vaccine (2023-2024 Formula); Comirnaty (COVID-19 Vaccine, mRNA) 2023-2024 Formula; Pfizer-BioNTech COVID-19 Vaccine (2024-2025 Formula); Comirnaty (COVID-19 Vaccine, mRNA) 2024-2025 Formula; Comirnaty Original/Omicron BA.1; Comirnaty Original/Omicron BA.4/BA.5; Comirnaty Omicron XBB.1.5; Comirnaty JN.1 and Comirnaty KP.2. “Comirnaty” includes product revenues and alliance revenues related to sales of the above-mentioned vaccines. (9) First-quarter 2024 Paxlovid revenue included a $771 million favorable final adjustment to the estimated non-cash revenue reversal of $3.5 billion recorded in fourth-quarter 2023, reflecting 5.1 million EUA-labeled treatment courses returned by the U.S. government through February 29, 2024 versus the estimated 6.5 million treatment courses that were expected to be returned as of December 31, 2023. (10) Keytruda® is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. DISCLOSURE NOTICE: Except where otherwise noted, the information contained in this earnings release and the related attachments is as of April 29, 2025. We assume no obligation to update any forward-looking statements contained in this earnings release and the related attachments as a result of new information or future events or developments. This earnings release and the related attachments contain forward-looking statements about, among other topics, our anticipated operating and financial performance, including financial guidance and projections; reorganizations; business plans, strategy, goals and prospects; expectations for our product pipeline, in-line products and product candidates, including anticipated regulatory submissions, data read-outs, study starts, approvals, launches, discontinuations, clinical trial results and other developing data, revenue contribution and projections, potential pricing and reimbursement, potential market dynamics, including demand, market size and utilization rates and growth, performance, timing of exclusivity and potential benefits; strategic reviews; leverage and capital allocation objectives; an enterprise-wide cost realignment program (including anticipated costs, savings and potential benefits); a Manufacturing Optimization Program to reduce our cost of goods sold (including anticipated costs, savings and potential benefits); dividends and share repurchases; plans for and prospects of our acquisitions, dispositions and other business development activities, including our December 2023 acquisition of Seagen, and our ability to successfully capitalize on growth opportunities and prospects; manufacturing and product supply; our ongoing efforts to respond to COVID-19; our expectations regarding the impact of COVID-19 on our business, operations and financial results; and the expected seasonality of demand for certain of our products. Given their forward-looking nature, these statements involve substantial risks, uncertainties and potentially inaccurate assumptions and we cannot assure that any outcome expressed in these forward-looking statements will be realized in whole or in part. You can identify these statements by the fact that they use future dates or use words such as “will,” “may,” “could,” “likely,” “ongoing,” “anticipate,” “estimate,” “expect,” “project,” “intend,” “plan,” “believe,” “assume,” “target,” “forecast,” “guidance,” “goal,” “objective,” “aim,” “seek,” “potential,” “hope” and other words and terms of similar meaning. Pfizer’s financial guidance is based on estimates and assumptions that are subject to significant uncertainties. Among the factors that could cause actual results to differ materially from past results and future plans and projected future results are the following: Risks Related to Our Business, Industry and Operations, and Business Development: the outcome of research and development (R&D) activities, including the ability to meet anticipated pre-clinical or clinical endpoints, commencement and/or completion dates for our pre-clinical or clinical trials, regulatory submission dates, and/or regulatory approval and/or launch dates; the possibility of unfavorable pre-clinical and clinical trial results, including the possibility of unfavorable new pre-clinical or clinical data and further analyses of existing pre-clinical or clinical data; risks associated with preliminary, early stage or interim data; the risk that pre-clinical and clinical trial data are subject to differing interpretations and assessments, including during the peer review/publication process, in the scientific community generally, and by regulatory authorities; whether and when additional data from our pipeline programs will be published in scientific journal publications, and if so, when and with what modifications and interpretations; and uncertainties regarding the future development of our product candidates, including whether or when our product candidates will advance to future studies or phases of development or whether or when regulatory applications may be filed for any of our product candidates; our ability to successfully address comments received from regulatory authorities such as the FDA or the EMA, or obtain approval for new products and indications from regulators on a timely basis or at all; regulatory decisions impacting labeling, approval or authorization, including the scope of indicated patient populations, product dosage, manufacturing processes, safety and/or other matters, including decisions relating to emerging developments regarding potential product impurities; uncertainties regarding the ability to obtain or maintain, and the scope of, recommendations by technical or advisory committees, and the timing of, and ability to obtain, pricing approvals and product launches, all of which could impact the availability or commercial potential of our products and product candidates; claims and concerns that may arise regarding the safety or efficacy of in-line products and product candidates, including claims and concerns that may arise from the conduct or outcome of post-approval clinical trials, pharmacovigilance or Risk Evaluation and Mitigation Strategies, which could impact marketing approval, product labeling, and/or availability or commercial potential; the success and impact of external business development activities, including the ability to identify and execute on potential business development opportunities; the ability to satisfy the conditions to closing of announced transactions in the anticipated time frame or at all; the ability to realize the anticipated benefits of any such transactions in the anticipated time frame or at all; the potential need for and impact of additional equity or debt financing to pursue these opportunities, which has in the past and could in the future result in increased leverage and/or a downgrade of our credit ratings and could limit our ability to obtain future financing; challenges integrating the businesses and operations; disruption to business or operations relationships; risks related to growing revenues for certain acquired or partnered products; significant transaction costs; and unknown liabilities; competition, including from new product entrants, in-line branded products, generic products, private label products, biosimilars and product candidates that treat or prevent diseases and conditions similar to those treated or intended to be prevented by our in-line products and product candidates; the ability to successfully market both new and existing products, including biosimilars; difficulties or delays in manufacturing, sales or marketing; supply disruptions, shortages or stock-outs at our facilities or third-party facilities that we rely on; and legal or regulatory actions; the impact of public health outbreaks, epidemics or pandemics (such as COVID-19) on our business, operations and financial condition and results, including impacts on our employees, manufacturing, supply chain, sales and marketing, R&D and clinical trials; risks and uncertainties related to Comirnaty and Paxlovid or any potential future COVID-19 vaccines, treatments or combinations, including, among others, the risk that as the market for COVID-19 products remains endemic and seasonal, demand for our COVID-19 products has and may continue to be reduced or not meet expectations, which has in the past and may continue to lead to reduced revenues, excess inventory or other unanticipated charges; risks related to our ability to develop and commercialize variant adapted vaccines, combinations and/or treatments; uncertainties related to recommendations and coverage for, and the public’s adherence to, vaccines, boosters, treatments or combinations; and potential third-party royalties or other claims related to Comirnaty and Paxlovid; trends toward managed care and healthcare cost containment, and our ability to obtain or maintain timely or adequate pricing or favorable formulary placement for our products; interest rate and foreign currency exchange rate fluctuations, including the impact of global trade tensions, as well as currency devaluations and monetary policy actions in countries experiencing high inflation or deflation rates; any significant issues involving our largest wholesale distributors or government customers, which account for a substantial portion of our revenues; the impact of the increased presence of counterfeit medicines, vaccines or other products in the pharmaceutical supply chain; any significant issues related to the outsourcing of certain operational and staff functions to third parties; any significant issues related to our JVs and other third-party business arrangements, including modifications or disputes related to supply agreements or other contracts with customers including governments or other payors; uncertainties related to general economic, political, business, industry, regulatory and market conditions including, without limitation, uncertainties related to the impact on us, our customers, suppliers and lenders and counterparties to our foreign-exchange and interest-rate agreements of challenging global economic conditions, such as inflation or interest rate fluctuations, and recent and possible future changes in global financial markets; the exposure of our operations globally to possible capital and exchange controls, economic conditions, expropriation, sanctions, tariffs and/or other restrictive government actions, changes in intellectual property legal protections and remedies, unstable governments and legal systems and inter-governmental disputes; risks and uncertainties related to issued or future executive orders or other new, or changes in, laws, regulations or policy regarding tariffs; the risk and impact of tariffs on our business, which is subject to a number of factors including, but not limited to, restrictions on trade, the effective date and duration of such tariffs, countries included in the scope of tariffs, changes to amounts of tariffs, and potential retaliatory tariffs or other retaliatory actions imposed by other countries; the impact of disruptions related to climate change and natural disasters; any changes in business, political and economic conditions due to actual or threatened terrorist activity, geopolitical instability, political or civil unrest or military action, including the ongoing conflicts between Russia and Ukraine and in the Middle East and the resulting economic or other consequences; the impact of product recalls, withdrawals and other unusual items, including uncertainties related to regulator-directed risk evaluations and assessments, such as our ongoing evaluation of our product portfolio for the potential presence or formation of nitrosamines, and our voluntary withdrawal of all lots of Oxbryta in all markets where it is approved and any regulatory or other impact on Oxbryta and other sickle cell disease assets; trade buying patterns; the risk of an impairment charge related to our intangible assets, goodwill or equity-method investments; the impact of, and risks and uncertainties related to, restructurings and internal reorganizations, as well as any other corporate strategic initiatives and growth strategies, and cost-reduction and productivity initiatives, including any potential future phases, each of which requires upfront costs but may fail to yield anticipated benefits and may result in unexpected costs, organizational disruption, adverse effects on employee morale, retention issues or other unintended consequences; the ability to successfully achieve our climate-related goals and progress our environmental sustainability and other priorities; Risks Related to Government Regulation and Legal Proceedings: the impact of any U.S. healthcare reform or legislation, including executive orders or other change in laws, regulations or policy, or any significant spending reduction or cost control efforts affecting Medicare, Medicaid, the 340B Drug Pricing Program or other publicly funded or subsidized health programs, including the Inflation Reduction Act of 2022 (IRA) and the IRA Medicare Part D Redesign, or changes in the tax treatment of employer-sponsored health insurance that may be implemented; U.S. federal or state legislation or regulatory action and/or policy efforts affecting, among other things, pharmaceutical product pricing, intellectual property, reimbursement or access to or recommendations for our medicines and vaccines, taxes or other restrictions on U.S. direct-to-consumer advertising; limitations on interactions with healthcare professionals and other industry stakeholders; as well as pricing pressures for our products as a result of highly competitive biopharmaceutical markets; risks and uncertainties related to potential changes to vaccine or other healthcare policy in the U.S.; legislation or regulatory action in markets outside of the U.S., such as China or Europe, including, without limitation, laws related to pharmaceutical product pricing, intellectual property, medical regulation, environmental protections, reimbursement or access, including, in particular, continued government-mandated reductions in prices and access restrictions for certain products to control costs in those markets; legal defense costs, insurance expenses, settlement costs and contingencies, including without limitation, those related to legal proceedings and actual or alleged environmental contamination; the risk and impact of an adverse decision or settlement and risk related to the adequacy of reserves related to legal proceedings; the risk and impact of tax related litigation and investigations; governmental laws, regulations and policies affecting our operations, including, without limitation, the IRA, as well as changes in such laws, regulations or policies or their interpretation, including, among others, changes in tariffs, tax laws and regulations internationally and in the U.S., the adoption of global minimum taxation requirements outside the U.S. generally effective in most jurisdictions since January 1, 2024, government cost-cutting measures and related impacts on, among other matters, government staffing, resources and ability to timely review and process regulatory or other submissions, and potential changes to existing tax laws, tariffs, or changes to other laws, regulations or policies in the U.S., including by the U.S. Presidential administration and Congress, as well as in other countries; Risks Related to Intellectual Property, Technology and Cybersecurity: the risk that our currently pending or future patent applications may not be granted on a timely basis or at all, or any patent-term extensions that we seek may not be granted on a timely basis, if at all; risks to our products, patents and other intellectual property, such as: (i) claims of invalidity that could result in loss of patent coverage; (ii) claims of patent infringement, including asserted and/or unasserted intellectual property claims; (iii) claims we may assert against intellectual property rights held by third parties; (iv) challenges faced by our collaboration or licensing partners to the validity of their patent rights; or (v) any pressure from, or legal or regulatory action by, various stakeholders or governments that could potentially result in us not seeking intellectual property protection or agreeing not to enforce or being restricted from enforcing intellectual property rights related to our products, including Comirnaty and Paxlovid; any significant breakdown or interruption of our information technology systems and infrastructure (including cloud services); any business disruption, theft of confidential or proprietary information, security threats on facilities or infrastructure, extortion or integrity compromise resulting from a cyber-attack, which may include those using adversarial artificial intelligence techniques, or other malfeasance by, but not limited to, nation states, employees, business partners or others; and risks and challenges related to the use of software and services that include artificial intelligence-based functionality and other emerging technologies. Should known or unknown risks or uncertainties materialize or should underlying assumptions prove inaccurate, actual results could vary materially from past results and those anticipated, estimated or projected. Investors are cautioned not to put undue reliance on forward-looking statements. A further list and description of risks, uncertainties and other matters can be found in our Annual Report on Form 10-K for the fiscal year ended December 31, 2024 and in our subsequent reports on Form 10-Q, in each case including in the sections thereof captioned “Forward-Looking Information and Factors That May Affect Future Results” and “Item 1A. Risk Factors,” and in our subsequent reports on Form 8-K. This earnings release may include discussion of certain clinical studies relating to various in-line products and/or product candidates. These studies typically are part of a larger body of clinical data relating to such products or product candidates, and the discussion herein should be considered in the context of the larger body of data. In addition, clinical trial data are subject to differing interpretations, and, even when we view data as sufficient to support the safety and/or effectiveness of a product candidate or a new indication for an in-line product, regulatory authorities may not share our views and may require additional data or may deny approval altogether. The information contained on our website or any third-party website is not incorporated by reference into this earnings release. All trademarks mentioned are the property of their owners. Certain of the products and product candidates discussed in this earnings release are being co-researched, co-developed and/or co-promoted in collaboration with other companies for which Pfizer’s rights vary by market or are the subject of agreements pursuant to which Pfizer has commercialization rights in certain markets.