Otitis Media

Millions of newly eligible U.S. adults aged 50 to 64 now recommended to receive vaccination against invasive pneumococcal disease (IPD) and pneumococcal pneumonia 1 NEW YORK--(BUSINESS WIRE)-- Pfizer Inc. (NYSE: PFE) announced today that the U.S. Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practice (ACIP) voted to expand its recommendation for the use of certain pneumococcal vaccines, including PREVNAR 20 ® (20-valent Pneumococcal Conjugate Vaccine) for all adults aged 50 and older. This recommendation is pending final approval by the director of the CDC and the Department of Health and Human Services. With respect to PREVNAR 20, ACIP recommended: Vaccination is recommended for all adults aged ≥50 years and for adults aged 19–49 years with certain underlying conditions or risk factors who have not received a PCV or whose vaccination history is unknown. “ACIP’s vote to expand adult pneumococcal vaccination to now include all adults aged 50 and older marks an important milestone in Pfizer’s long-standing commitment to reducing the burden of this life-threatening disease,” said Luis Jodar, PhD, Senior Vice President, Vaccines and Anti-Infectives Chief Medical Affairs Officers, Pfizer. “PREVNAR 20 offers protection against the serotypes responsible for the majority of invasive pneumococcal disease cases in this age group. Expanding its use also provides an opportunity to limit the re-emergence of disease-causing strains like serotype 4, which has recently affected certain U.S. adult populations and is covered by the vaccine.” In the U.S., the 20 serotypes contained in PREVNAR 20 are estimated to cause over 2,000 deaths and more than 65,000 cases of invasive pneumococcal disease (IPD), including bacteremia and meningitis, and community-acquired pneumonia annually in adults aged 50 to 64. 2 Between 2018 and 2022, more than half of IPD cases in people aged 50 to 64 were caused by these 20 serotypes. 3 Vaccination with PREVNAR 20 helps prevent serotype 4 disease, which incidence has been rising in certain populations in the western U.S. 4 About PREVNAR 20 ® PREVNAR 20 ® is Pfizer’s next-generation pneumococcal conjugate vaccine that includes capsular polysaccharide conjugates for the 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) already included in Prevnar 13 ® (Pneumococcal 13-valent Conjugate Vaccine [Diphtheria CRM197 Protein]). The vaccine also contains capsular polysaccharide conjugates for seven additional serotypes (8, 10A, 11A, 12F, 15B, 22F and 33F) that cause invasive pneumococcal disease (IPD), 5,6,7,8,9 and have been associated with high case-fatality rates, 10,11,12,13 antibiotic resistance, 14,15,16 and/or meningitis. 17,18 PREVNAR 20 helps protect against disease caused by the 20 Streptococcus pneumoniae serotypes in the vaccine. On June 8, 2021, Pfizer announced the U.S. Food and Drug Administration (FDA) approved PREVNAR 20 for the prevention of invasive pneumococcal disease and pneumococcal pneumonia in adults aged 18 years or older. On September 30, 2022, the FDA approved the addition of information in the PREVNAR 20 prescribing information regarding coadministration with an influenza vaccine, adjuvanted (Fluad Quadrivalent 19 ), in adults aged 65 years or older. INDICATIONS FOR PREVNAR 20 PREVNAR 20 ® is a vaccine indicated for: the prevention of invasive disease caused by 20 Streptococcus pneumoniae strains (1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F) in individuals 6 weeks and older. the prevention of otitis media (middle ear infection) caused by 7 of the 20 strains in individuals 6 weeks through 5 years. active immunization for the prevention of pneumonia caused by Streptococcus pneumoniae strains 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, and 33F in individuals 18 years of age and older. The indication of PREVNAR 20 for the prevention of pneumonia caused by S. pneumoniae serotypes 8, 10A, 11A, 12F, 15B, 22F, and 33F in individuals 18 years of age and older is approved based on immune responses. Continued approval may depend on a supportive study IMPORTANT SAFETY INFORMATION FOR PREVNAR 20 PREVNAR 20 ® should not be given to anyone who has had a severe allergic reaction to any component of PREVNAR 20 or to diphtheria–toxoid-containing vaccine. Individuals with weakened immune systems may have a lower immune response. Safety data are not available for these groups. A temporary pause in breathing after getting the vaccine has been observed in some infants who were born prematurely. For premature infants, talk to your doctor about the infant's medical status when deciding to get vaccinated with PREVNAR 20. In individuals 2, 4, 6, and 12 through 15 months of age vaccinated with a 4-dose schedule, the most common side effects reported at a rate of >10% were irritability, pain at the injection site, drowsiness, decreased appetite and injection site redness, injection site swelling, and fever. In individuals 15 months through 17 years of age vaccinated with a single dose, the most common side effects reported at a rate of >10% were irritability, pain at the injection site, drowsiness, fatigue and muscle pain, decreased appetite, injection site swelling and injection site redness, headache, and fever. In individuals 18 years and older, the most common side effects reported at a rate of >10% were pain at the injection site, muscle pain, fatigue, headache, and joint pain. Also, injection site swelling was common in individuals 18 years through 59 years of age. Ask your doctor about the risks and benefits of PREVNAR 20. Only a doctor can decide if PREVNAR 20 is right for you or your child. View the full Prescribing Information. About Pfizer: Breakthroughs That Change Patients’ Lives At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world's premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For 175 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.Pfizer.com. In addition, to learn more, please visit us on www.Pfizer.com and follow us on X at @Pfizer and @Pfizer News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer. DISCLOSURE NOTICE: The information contained in this release is as of October 23, 2024. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments. This release contains forward-looking information about PREVNAR 20 ® (20-valent Pneumococcal Conjugate Vaccine), including its potential benefits and a vote by ACIP to expand its recommendation for the use of certain pneumococcal vaccines, including PREVNAR 20 for all adults aged 50 and older and for adults aged 19–49 years with certain underlying conditions or risk factors who have not received a PCV or whose vaccination history is unknown, that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, uncertainties regarding the commercial success of PREVNAR 20 and uncertainties regarding the commercial impact of ACIP’s recommendation; the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for our clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as the possibility of unfavorable new clinical data and further analyses of existing clinical data; the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; whether regulatory authorities will be satisfied with the design of and results from our clinical studies; whether and when any biologics license applications may be filed in any other jurisdictions for PREVNAR 20 for any potential indications; whether and when any such applications that may be pending or filed may be approved by regulatory authorities, which will depend on myriad factors, including making a determination as to whether the product’s benefits outweigh its known risks and determination of the product’s efficacy and, if approved, whether PREVNAR 20 will be commercially successful; decisions by regulatory authorities impacting labeling, manufacturing processes, safety and/or other matters that could affect the availability or commercial potential of PREVNAR 20; uncertainties regarding the ability to obtain recommendations from vaccine advisory or technical committees and other public health authorities regarding PREVNAR 20 and uncertainties regarding the commercial impact of any such recommendations; uncertainties regarding the impact of COVID-19 on our business, operations and financial results; and competitive developments. A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2023, and in its subsequent reports on Form 10-Q, including in the sections thereof captioned “Risk Factors” and “Forward-Looking Information and Factors That May Affect Future Results”, as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at www.sec.gov and www.pfizer.com . ________________________________ 1 U.S. Census Bureau. Population by age. https://data.census.gov/table?q=Population%20by%20age. Accessed October 2024. 2 Perdrizet J, Chilson E, Wasserman M, et al. Current and future pneumococcal conjugate vaccine serotype-specific burden in the United States adult population. Abstract No. ISP20-287 Presented at ISPPD-12, Toronto, June 21-25, 2020. Available at: https://cslide.ctimeetingtech.com/isppd20/attendee/confcal/presentation/list?q=Perdrizet. 3 U.S. Centers for Disease Control and Prevention. Summary of Work Group Interpretations of EtR and Policy Option on PCV21 Use in Adults. https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/04-Pneumococcal-Kobayashi-508.pdf. Presented June 27, 2024. Accessed October 11, 2024. 4 U.S. Centers for Disease Control and Prevention. Summary of Risk-based Pneumococcal Vaccination Recommendations. https://www.cdc.gov/pneumococcal/hcp/vaccine-recommendations/risk-indications.html. Updated October 10, 2024. Accessed October 11, 2024. 5 Baisells E, Guillot L, Nair H, et al. Serotype distribution of Streptococcus pneumoniae causing invasive disease in children in the post-PCV era: A systematic review and meta-analysis. PlosOne. 2017;12(5): e0177113. 6 Hausdorff W & Hanage W. Interim results of an ecological experiment – conjugate vaccination against the pneumococcus and serotype replacement. Hum Vaccin Immunother. 2016;12(2):358-374. 7 Cohen R, Cohen J, Chalumeau M, et al. Impact of pneumococcal conjugate vaccines for children in high- and non-high income countries. Expert Rev Vaccines. 2017;16(6):625-640. 8 Moore M, Link-Gelles R, Schaffner W, et al. Effect of use of 13-valent pneumococcal conjugate vaccine in children on invasive pneumococcal disease in children and adults in the USA: analysis of multisite, population-based surveillance. Lancet Infect Dis. 2015;15(3):301-309. 9 Metcalf B, Gertz RE, Gladstone RA, et al. Strain features and distributions in pneumococci from children with invasive disease before and after 13-valent conjugate vaccine implementation in the USA. Clin Microbiol Infect. 2016;22(1):60.e9-60.e29. 10 Oligbu G, Collins S, Sheppard CL, et al. Childhood deaths attributable to invasive pneumococcal disease in England and Wales, 2006–2014. Clin Infect Dis. 2017;65(2):308-314. 11 van Hoek, Andrews N, Waight PA, et al. Effect of serotype on focus and mortality of invasive pneumococcal disease: Coverage of different vaccines and insight into non-vaccine serotypes. PlosOne. 2012;7(7):e39150. 12 Stanek R, Norton N, Mufson M. A 32-years study of the impact of pneumococcal vaccines on invasive Streptococcus pneumoniae disease. Am J Med Sci. 2016;352(6):563-573. 13 Harboe ZB, Thomsen RW, Riis A, et al. Pneumococcal serotypes and mortality following invasive pneumococcal disease: A population-based cohort study. PlosOne. 2009;6(5):e1000081. 14 Azzari C, Cortimiglia M, Nieddu F, et al. Pneumococcal serotype distribution in adults with invasive disease and in carrier children in Italy: Should we expect herd protection of adults through infants’ vaccination? Hum Vaccin Immunother. 2016;12(2):344-350. 15 Tomczyk S, Lynfield R, Schaffner W, et al. Prevention of antibiotic-nonsusceptible invasive pneumococcal disease with the 13-valent pneumococcal conjugate vaccine. Clin Infect Dis. 2016;62(9):1119-1125. 16 Mendes RE, Hollingsworth RC, Costello A, et al. Noninvasive Streptococcus pneumoniae serotypes recovered from hospitalized adult patients in the United States in 2009 to 2012. Antimicrob Agents Chemother. 2015;59(9):5595-5601. 17 Olarte L, Barson WJ, Lin PL, et al. Impact of the 13-valent pneumococcal conjugate vaccine on pneumococcal meningitis in US children. Clin Infect Dis. 2015;61(5):767-775. 18 Thigpen MC, Whitney CG, Messonnier NE, et al. Bacterial meningitis in the United States, 1998–2007. NEJM. 2011;364(21):2016-2025. 19 Fluad Quadrivalent is not a Pfizer product Category: Vaccines Media Contact: PfizerMediaRelations@Pfizer.com +1 (212) 733-1226 Investor Contact: IR@Pfizer.com +1 (212) 733-4848 Source: Pfizer Inc.

— At All Doses Studied, VAX-31 Demonstrated Robust Opsonophagocytic Activity Immune Responses for All 31 Serotypes — — At Middle and High Doses, VAX-31 Met or Exceeded Regulatory Immunogenicity Criteria for All 31 Serotypes — — At All Doses Studied, VAX-31 Was Observed to be Well Tolerated and Demonstrated a Safety Profile Similar to Prevnar 20 ® — — Topline Results Further Validate Potential of Vaxcyte’s Carrier-Sparing Platform to Deliver Broadest-Spectrum Pneumococcal Conjugate Vaccine Candidates that Provide Protection Against Both Currently Circulating and Historically Prevalent Serotypes — — For Adult Indication, VAX-31 Selected to Advance to Phase 3 Program; Vaxcyte Plans to Initiate Phase 3 Pivotal, Non-Inferiority Study by Mid-2025 and Announce Topline Safety, Tolerability and Immunogenicity Data in 2026 — — For Pediatric Indication, in Parallel with Ongoing VAX-24 Study, Company Plans to Initiate VAX-31 Infant Phase 2 Study in First Quarter of 2025 Following IND Application Submission and Clearance — SAN CARLOS, CA, USA I September 03, 2024 I Vaxcyte, Inc. (Nasdaq: PCVX), a clinical-stage vaccine innovation company engineering high-fidelity vaccines to protect humankind from the consequences of bacterial diseases, today announced positive topline results from the Phase 1/2 study evaluating the safety, tolerability and immunogenicity of VAX-31, the Company’s 31-valent pneumococcal conjugate vaccine (PCV) candidate designed to prevent invasive pneumococcal disease (IPD), in 1,015 healthy adults aged 50 and older. Based on the strength of the results from this study, the Company has selected VAX-31 to advance to an adult Phase 3 program. In this Phase 1/2 study, VAX-31 was observed to be well tolerated and demonstrated a safety profile at all doses studied through the full six-month evaluation period similar to Prevnar 20 ® (PCV20). VAX-31 showed robust opsonophagocytic activity (OPA) immune responses for all 31 serotypes at all doses studied. At the middle and high doses, VAX-31 met or exceeded the OPA response non-inferiority criteria (1) for all 20 serotypes common with PCV20. At the VAX-31 high dose, average OPA immune responses were greater for 18 of 20 serotypes compared to PCV20 (geometric mean ratio (GMR) greater than 1.0), with seven of these serotypes achieving statistically higher immune responses (2) compared to PCV20. At the middle dose, 13 of 20 serotypes had a GMR greater than 1.0 and five serotypes achieved statistically higher immune responses compared to PCV20. For all 11 incremental serotypes unique to VAX-31, and not in PCV20, all three doses met the superiority criteria (3) . The Company plans to select the VAX-31 dose prior to the initiation of the adult Phase 3 program. “We believe the positive safety, tolerability and immunogenicity results from the VAX-31 Phase 1/2 study affirm the potential of our site-specific, carrier-sparing platform to deliver the broadest-spectrum PCVs that provide protection against both currently circulating and historically prevalent strains,” said Grant Pickering, Chief Executive Officer and Co-Founder of Vaxcyte. “Based on the strength and clarity of these data, we have selected VAX-31 for the adult indication and plan to initiate the pivotal, non-inferiority Phase 3 study by mid-2025 and announce topline data in 2026. We intend to initiate the remaining VAX-31 Phase 3 studies in 2025 and 2026 and submit a Biologics License Application subject to the results of these studies.” “We are exceptionally proud to share these results, which we believe validate VAX-31’s potential as a best-in-class pneumococcal vaccine capable of raising the bar for immunogenicity standards,” said Jim Wassil, Executive Vice President and Chief Operating Officer of Vaxcyte. “The public health community continues to highlight the need for broader-protection vaccines to prevent IPD, which is associated with high case-fatality rates, antibiotic resistance and meningitis. To address this need, VAX-31 was designed to increase coverage to more than 95% of IPD circulating in adults 50 and older in the United States, with the potential to provide significantly greater coverage relative to today’s standard-of-care adult PCVs. We want to extend our sincere gratitude to everyone involved in this program, especially the study participants, trial investigators and sites, and the entire Vaxcyte team.” Key Topline Study Results Safety and Tolerability Findings: Immunogenicity Findings: VAX-31 showed robust OPA immune responses for all 31 serotypes at all doses studied, and all three doses would be advanceable to Phase 3. About the VAX-31 Phase 1/2 Clinical Study The VAX-31 Phase 1/2 clinical study was a randomized, observer-blind, active-controlled, dose-finding clinical study designed to evaluate the safety, tolerability and immunogenicity of a single injection of VAX-31 at three dose levels (low, middle and high) and compared to PCV20 in 1,015 healthy adults aged 50 and older. In the low, middle and high doses, all serotypes were dosed at 1.1mcg, 2.2mcg and 3.3mcg, respectively, except serotypes 1, 5 and 22F, which were dosed at 1.65mcg, 3.3mcg, and 4.4mcg, respectively. The Phase 1 portion of the study included 64 healthy adults 50 to 64 years of age and the Phase 2 portion included 951 healthy adults 50 years of age and older. The immunogenicity objectives of the study included an assessment of the induction of antibody responses at Month 1, based on OPA and immunoglobulin G (IgG), at each of the three VAX-31 doses and compared to PCV20 for the 20 serotypes in common, as well as for the additional 11 serotypes contained in VAX-31, but not in PCV20. The study enrolled subjects from 25 sites in the United States. Additional information about the study can be found at www.clinicaltrials.gov under the identifier NCT06151288 . Key Anticipated PCV Franchise Milestones Vaxcyte is advancing the clinical development of its PCV programs with several anticipated key milestones, including: Adult: VAX-31 Infant: VAX-24 VAX-31 Conference Call and Webcast Vaxcyte will hold a webcast and conference call today, September 3 at 8:00 a.m. ET to discuss the results from the VAX-31 Phase 1/2 study. To participate in the conference call, please dial 800-225-9448 (domestic) or 203-518-9708 (international) and refer to conference ID PCVX0903. A live webcast of the conference call will also be available on the investor relations page of the Vaxcyte corporate website at www.vaxcyte.com . After the live webcast, the event will remain archived on the Vaxcyte website for 30 days. About Pneumococcal Disease Pneumococcal disease (PD) is an infection caused by Streptococcus pneumoniae (pneumococcus) bacteria. It can result in invasive pneumococcal disease (IPD), including meningitis and bacteremia, and non-invasive PD, including pneumonia, otitis media and sinusitis. In the United States, pneumococcal pneumonia is estimated to result in approximately 150,000 hospitalizations each year. Streptococcus pneumoniae is among the World Health Organization’s top antibiotic-resistant pathogens to be urgently addressed, and the U.S. CDC lists drug-resistant Streptococcus pneumoniae as a “serious threat.” Streptococcus pneumoniae is the leading cause of vaccine-preventable deaths in children under five globally. Pneumococci also cause over 50% of all cases of bacterial meningitis in the United States. Antibiotics are used to treat PD, but some strains of the bacteria have developed resistance to treatments. The morbidity and mortality due to PD are significant, particularly for young children and older adults, underscoring the need for a broader-spectrum vaccine. About VAX-31 VAX-31, a 31-valent PCV candidate advancing to a Phase 3 adult clinical program, is designed to prevent IPD, which is especially serious in infants, young children, older adults and those with immune deficiencies or certain chronic health conditions. IPD is associated with high case-fatality rates, antibiotic resistance and meningitis. VAX-31 is the broadest-spectrum PCV in the clinic and has the potential to provide protection against both currently circulating and historically prevalent serotypes. VAX-31 was designed to increase coverage to more than 95% of IPD circulating in adults in the United States aged 50 and older, with the potential to provide an incremental 12-40% of coverage over current standard-of-care adult PCVs. About Vaxcyte Vaxcyte is a vaccine innovation company engineering high-fidelity vaccines to protect humankind from the consequences of bacterial diseases. The Company is developing broad-spectrum conjugate and novel protein vaccines to prevent or treat bacterial infectious diseases. VAX-31 is a Phase 3-ready 31-valent, carrier-sparing PCV being developed for the prevention of IPD in adults and infants and is the broadest-spectrum PCV candidate in the clinic today. VAX-24, the Company’s 24-valent PCV candidate, is designed to cover more serotypes than any infant PCV on-market and is currently being evaluated in a Phase 2 infant study. Both VAX-31 and VAX-24 are designed to improve upon the standard-of-care PCVs by covering the serotypes in circulation that are responsible for a significant portion of IPD and are associated with high case-fatality rates, antibiotic resistance and meningitis, while maintaining coverage of previously circulating strains that are currently contained through continued vaccination practice. Vaxcyte is re-engineering the way highly complex vaccines are made through modern synthetic techniques, including advanced chemistry and the XpressCF™ cell-free protein synthesis platform, exclusively licensed from Sutro Biopharma, Inc. Unlike conventional cell-based approaches, the Company’s system for producing difficult-to-make proteins and antigens is intended to accelerate its ability to efficiently create and deliver high-fidelity vaccines with enhanced immunological benefits. Vaxcyte’s pipeline also includes VAX-A1, a prophylactic vaccine candidate designed to prevent Group A Strep infections; VAX-PG, a therapeutic vaccine candidate designed to slow or stop the progression of periodontal disease; and VAX-GI, a vaccine candidate designed to prevent Shigella. Vaxcyte is driven to eradicate or treat invasive bacterial infections, which have serious and costly health consequences when left unchecked. For more information, visit www.vaxcyte.com . Lower bound of the 2-sided 95% confidence interval of the OPA geometric mean ratio is greater than 0.5. (2) Lower bound of the 2-sided 95% confidence interval of the OPA geometric mean ratio is greater than 1.0. (3) Lower bound of the 2-sided 95% confidence interval of the difference in the proportions of participants with a ≥4-fold increase from Day 1 to Month 1 is greater than 10%, and lower bound of the 2-sided 95% confidence interval of the OPA geometric mean ratio is greater than 2.0. SOURCE: Vaxcyte

Long-term safety and tolerability profile consistent with pivotal data in atopic dermatitis (AD), with no new safety signals observed during 56 weeks of treatmentResults from open-label extension study highlight that 71.9% of patients who rolled over from the roflumilast cream treatment arm in INTEGUMENT-PED achieved EASI-75 at Week 56Arcutis intends to submit a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) in the first quarter of 2025 for roflumilast cream 0.05% WESTLAKE VILLAGE, Calif., Aug. 28, 2024 (GLOBE NEWSWIRE) -- Arcutis Biotherapeutics, Inc. (NASDAQ: ARQT), a commercial-stage biopharmaceutical company focused on developing meaningful innovations in immuno-dermatology, today announced results from the INTEGUMENT-OLE long-term open-label study of once-daily roflumilast cream 0.05% demonstrating the durable efficacy and favorable safety profile of roflumilast cream 0.05% in the treatment of mild to moderate AD in children 2 to 5 years old. In the study, roflumilast cream was well-tolerated, with no new safety signals observed during treatment of up to 56 weeks in duration. Efficacy was not only maintained but improved over time, with 71.9% of participants who rolled over from the roflumilast cream 0.05% treatment arm in INTEGUMENT-PED achieving 75% improvement from baseline in Eczema Area and Severity Index (EASI-75) after 56 weeks. “When choosing a therapy for very young children, health care providers and caregivers are looking for treatments that provide both rapid relief and are well-tolerated and suitable for long-term use,” said Adelaide Hebert, MD, professor of dermatology and pediatrics at UTHealth Houston, and INTEGUMENT trial investigator. “These results build upon the findings from the Phase 3 trial of roflumilast cream 0.05% that demonstrated rapid efficacy within the first 4 weeks of treatment, and further showed long-term durable efficacy and tolerability of investigational roflumilast cream, with continued improvement over the course of the long-term study.” In the study, 53.8% of participants who rolled over from the roflumilast cream treatment arm in INTEGUMENT-PED achieved a validated Investigator Global Assessment-Atopic Dermatitis (vIGA-AD) success, defined as vIGA-AD value of 0 or 1 plus a 2-grade improvement from baseline, at 56 weeks. The long-term study results reinforce the safety and tolerability profile of roflumilast cream 0.05% already seen in the 4-week pivotal INTEGUMENT-PED clinical trial, with no new safety signals observed up to 56 weeks. Overall incidence of adverse events was low, with most being mild to moderate in nature. The most frequently reported adverse events (≥3%) included: upper respiratory tract infection, nasopharyngitis, pyrexia, influenza, COVID-19, and otitis media. Overall, only 3.0% of trial participants discontinued the study due to adverse events. “Roflumilast cream is uniquely formulated with the AD patient in mind, to deliver treatment without sensitizing excipients and irritants, which can often disrupt the skin barrier. We are excited by these results, which reinforce the strength of our ZORYVE product portfolio and specifically demonstrate the long-term efficacy, safety and tolerability profile of our once-daily roflumilast cream for the treatment of pediatric AD,” said Patrick Burnett, MD, PhD, FAAD, chief medical officer at Arcutis. “Based on these positive results, we are convinced that, if approved, roflumilast cream 0.05% can help provide immediate as well as long-term management of this burdensome skin condition, expanding the treatment population to children down to age 2.” Arcutis intends to submit an sNDA to the FDA in the first quarter of 2025 for roflumilast cream 0.05% for the treatment of AD in individuals ages 2-5 years. ZORYVE® (roflumilast) cream 0.15% is approved for the topical treatment of mild to moderate AD in adults and pediatric patients down to age 6. About INTEGUMENT-OLEThe “INterventional Trial EvaluatinG roflUMilast cream for the treatmENt of aTopic dermatitis Open Label Extension (INTEGUMENT-OLE) was a Phase 3, multicenter, open-label extension study of the long-term safety of roflumilast cream 0.15% in adults and children ages 6 years and older with AD and roflumilast cream 0.05% in children ages 2 to 5 years. A total of 562 individuals enrolled in the study after completing the INTEGUMENT-PED Phase 3 trial. The study evaluated monotherapy with roflumilast cream 0.05% with no rescue treatment permitted. Beginning at Week 4 of INTEGUMENT-OLE, any participant who achieved vIGA-AD of ‘0-Clear’ switched to twice weekly maintenance treatment. Participants were able to continue twice weekly maintenance dosing, as long as vIGA-AD remained either ‘0‑Clear’ or ‘1-Almost Clear’. Participants resumed once-daily dosing if vIGA-AD reached ≥2-Mild, and could also resume once-daily dosing if signs/symptoms of AD were not adequately controlled with maintenance therapy. The primary objective of the study was to assess the long-term safety of roflumilast cream. Secondary endpoints included vIGA-AD score of 0 or 1 at each assessment, vIGA-AD success defined as vIGA-AD value of 0 or 1 plus a 2-grade improvement from baseline, and Eczema Area and Severity Index (EASI) score over time. The assessment of vIGA-AD Success and EASI-75 response, as reported here, references baseline of INTEGUMENT-PED. About Atopic DermatitisAD is the most common type of eczema, affecting approximately 9.6 million children and 16.5 million adults in the United States. AD is characterized by a defect in the skin barrier, which allows allergens and other irritants to enter the skin, leading to an immune reaction and inflammation. This reaction produces a red, itchy rash, most frequently occurring on the face, arms, and legs. The rash can cover significant areas of the body, in some cases half of the body or more. AD typically begins in early childhood and is chronic. It persists into adolescence and even adulthood in some individuals. The rash causes significant pruritus (itching), which can lead to skin damage caused by scratching or rubbing. Since a large percentage of AD patients are very young children, safety is a particularly important consideration in treatment selection. About Roflumilast CreamRoflumilast cream is a next generation topical phosphodiesterase-4 (PDE4) inhibitor. PDE4 – an established target in dermatology – is an intracellular enzyme that increases the production of pro-inflammatory mediators and decreases production of anti-inflammatory mediators. Roflumilast cream 0.3% (ZORYVE®) is approved by the FDA for the topical treatment of plaque psoriasis, including intertriginous areas, in patients 6 years of age and older. Roflumilast cream 0.15% (ZORYVE®) is approved by the U.S. Food and Drug Administration (FDA) for the topical treatment of mild to moderate atopic dermatitis, in patients 6 years of age and older. A lower dose, roflumilast cream 0.05%, was evaluated for children aged 2 to 5 years. INDICATIONSZORYVE cream, 0.3%, is indicated for topical treatment of plaque psoriasis, including intertriginous areas, in adult and pediatric patients 6 years of age and older. ZORYVE cream, 0.15%, is indicated for topical treatment of mild to moderate atopic dermatitis in adult and pediatric patients 6 years of age and older. IMPORTANT SAFETY INFORMATION ZORYVE is contraindicated in patients with moderate to severe liver impairment (Child-Pugh B or C). The most common adverse reactions (≥1%) for ZORYVE cream 0.3% include diarrhea (3.1%), headache (2.4%), insomnia (1.4%), nausea (1.2%), application site pain (1.0%), upper respiratory tract infection (1.0%), and urinary tract infection (1.0%). The most common adverse reactions (≥1%) for ZORYVE cream 0.15% for atopic dermatitis include headache (2.9%), nausea (1.9%), application site pain (1.5%), diarrhea (1.5%), and vomiting (1.5%). Please see full Prescribing Information. About ArcutisArcutis Biotherapeutics, Inc. (Nasdaq: ARQT) is a commercial-stage medical dermatology company that champions meaningful innovation to address the urgent needs of individuals living with immune-mediated dermatological diseases and conditions. With a commitment to solving the most persistent patient challenges in dermatology, Arcutis has a growing portfolio including three FDA approved products that harness our unique dermatology development platform coupled with our dermatology expertise to build differentiated therapies against biologically validated targets. Arcutis’ dermatology development platform includes a robust pipeline with multiple clinical programs for a range of inflammatory dermatological conditions including scalp and body psoriasis, AD. and alopecia areata. For more information, visit www.arcutis.com or follow Arcutis on LinkedIn, Facebook, Instagram, and X. Forward-Looking StatementsArcutis cautions you that statements contained in this press release regarding matters that are not historical facts are forward-looking statements. These statements are based on the Company’s current beliefs and expectations. Such forward-looking statements include, but are not limited to, statements regarding the potential and timing for roflumilast cream to be approved by the FDA for the treatment of children ages 2 to 5 with AD, the potential to use roflumilast cream in those ages over a long period of time, or chronically, the potential to use roflumilast cream anywhere on the body, and the potential for roflumilast cream to advance the standard of care in AD and other inflammatory dermatological conditions. These statements are subject to substantial known and unknown risks, uncertainties and other factors that may cause our actual results, levels of activity, performance, or achievements to be materially different from the information expressed or implied by these forward-looking statements. Risks and uncertainties that may cause our actual results to differ include risks inherent in our business, reimbursement and access to our products, and the impact of competition and other important factors discussed in the “Risk Factors” section of our Form 10-K filed with the U.S. Securities and Exchange Commission (SEC) on February 27, 2024, as well as any subsequent filings with the SEC. You should not place undue reliance on any forward-looking statements in this press release. We undertake no obligation to revise or update information herein to reflect events or circumstances in the future, even if new information becomes available. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Contacts:MediaAmanda Sheldon, Head of Corporate Communicationsmedia@arcutis.com InvestorsLatha Vairavan, Vice President, Finance and Corporate Controllerir@arcutis.com