Oxcarbazepine

February 25, 2026 12:37 pm EST DOR/ISL is the first non-INSTI, two-drug regimen to demonstrate non-inferiority and a similar safety profile at Week 48 to BIC/FTC/TAF in adults living with HIV-1 who had not previously received antiretroviral treatment DOR/ISL maintained virologic suppression at Week 96 in adults with virologically suppressed HIV-1 who switched from other oral antiretroviral therapies, including BIC/FTC/TAF RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced the presentation of results from three pivotal Phase 3 trials evaluating the investigational, once-daily, oral, two-drug regimen of doravirine/islatravir [DOR/ISL (100 mg/0.25 mg), (MK-8591A)] in adults with HIV-1. The findings were shared in late-breaking presentations at the 33rd Conference on Retroviruses and Opportunistic Infections (CROI) being held in Denver. “We are proud to continue building on our 40-year history of HIV research with the presentation of compelling new data from our HIV pipeline at CROI this year,” said Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories. “Islatravir blocks HIV-1 replication through multiple mechanisms, including reverse transcriptase translocation inhibition, and could serve as the anchor for a series of two-drug, non-INSTI, daily and weekly treatment regimens. If approved, DOR/ISL will be the first of these regimens in our portfolio and may provide an important new option to help meet the evolving treatment needs of people living with HIV.” The Phase 3, double-blind, clinical trial MK-8591A-053 evaluating DOR/ISL versus bictegravir/emtricitabine/tenofovir alafenamidei [(50 mg/200 mg/25 mg),(BIC/FTC/TAF)] in adults living with HIV-1 who had not previously received antiretroviral treatment (treatment-naïve), met its primary efficacy endpoint of percentage of participants achieving viral suppression (HIV-1 RNA <50 copies/mL), demonstrating non-inferiority for DOR/ISL compared to BIC/FTC/TAF at Week 48, 91.8% and 90.6% respectively (treatment difference 1.2%, 95% CI: -3.7, 6.2, p<0.001). The safety profile was similar between both treatment groups and consistent with that observed in previous studies. Drug-related adverse events (AEs) and discontinuations due to drug-related AEs were similar between groups (14% for DOR/ISL and 18% for BIC/FTC/TAF; 1.1% for DOR/ISL and 2.2% for BIC/FTC/TAF, respectively). These data, which are being published simultaneously in The Lancet HIV, build on the previously reported Phase 3 data in adults with virologically suppressed HIV-1 and will form the basis of future regulatory applications. “These new Phase 3 results are meaningful, showing that an investigational two-drug regimen without an INSTI demonstrated non-inferior efficacy and a comparable safety profile versus BIC/FTC/TAF in previously untreated adults with HIV-1, including those with advanced disease,” said Dr. Jürgen K. Rockstroh, professor of medicine, head of the HIV Outpatient Clinic at the University of Bonn. “This study evaluated a diverse, global population, and included a significant proportion of participants with high viral loads and low CD4 counts. These findings add to the growing evidence supporting the potential role of DOR/ISL in HIV care.” New 96-week data from the Phase 3 MK-8591A-052 and MK-8591A-051 trials evaluating DOR/ISL vs. BIC/FTC/TAF or baseline antiretroviral therapy (bART), in participants with virologically suppressed HIV-1 and who were switched to DOR/ISL, were also presented. In both trials, DOR/ISL maintained high rates of viral suppression at Week 96 and had a similar safety profile to BIC/FTC/TAF and bART. The 48-week data from these trials supported the initial New Drug Application (NDA) for DOR/ISL for the treatment of HIV-1 infection in adults who are virologically-suppressed on a stable antiretroviral regimen; the U.S. FDA has set a target action date of April 28, 2026 for the application under the Prescription Drug User Fee Act (PDUFA). In the U.S., doravirine is approved for the treatment of adults with HIV-1 in combination with other antiretrovirals as a single agent (PIFELTRO) and a component of a single-tablet regimen [DELSTRIGO; doravirine, lamivudine, and tenofovir disoproxil fumarate (DOR/3TC/TDF)]. “As people living with HIV age, managing other health conditions becomes a reality for many, making it especially important to have treatment options that can help meet each person’s unique health needs,” said Dr. Amy Colson, director of research at Community Resource Initiative, Cambridge, Massachusetts. “Over time, people may need to adjust their HIV treatment regimens because of comorbidities, concerns about toxicities, tolerability challenges, or a desire for regimens with fewer medications. These 96-week data are encouraging, showing a non-INSTI option like investigational DOR/ISL could offer an important alternative.” About the Phase 3 data from MK-8591A-053 MK-8591A-053 is an ongoing Phase 3 randomized, active-controlled, double-blind, clinical trial evaluating the efficacy and safety of investigational, once-daily DOR/ISL (100 mg/0.25 mg) versus BIC/FTC/TAF in adults living with HIV-1 infection who had not previously received antiretroviral treatment. Participants were randomized 1:1 to DOR/ISL (n=269) or BIC/FTC/TAF (with matching placebos) (n=267), stratified by screening CD4+ T-cell count (<200 cells/mm³) and HIV-1 RNA (>100,000 copies/mL). The primary efficacy endpoint was the percentage of participants with HIV-1 RNA <50 copies/mL at Week 48 (non-inferiority margin 10%). Of the total participants enrolled in the trial, 36.8% had baseline HIV-1 RNA >100,000 copies/mL, 10.3% had HIV-1 RNA >500,000 copies/mL and 17.2% had baseline CD4+ T-cell count <200 cells/mm3. At Week 48, virological efficacy as measured by the percentage of participants with HIV-1 RNA levels < 50 copies/mL, was comparable in participants on DOR/ISL versus BIC/FTC/TAF with screening HIV-1 RNA >100,000 copies/mL (94.0% vs 87.6%, respectively) and >500,000 copies/mL (90.3% vs 84.4%, respectively). Drug-related AEs were reported in 14.1% of participants on DOR/ISL and 18.0% on BIC/FTC/TAF and discontinuations due to AEs (1.1% vs. 2.2%) were similar in both groups. Immune reconstitution was similar in DOR/ISL vs. comparator with no between-group differences in mean increases in CD4+ T-cell counts or total lymphocyte counts (TLC). About the Phase 3 data from MK-8591A-052 MK-8591A-052 is a Phase 3, randomized, active-controlled, double-blind, clinical trial to evaluate the efficacy and safety of a switch to investigational, once-daily DOR/ISL (100 mg/0.25 mg) in adults with HIV-1 infection that has been virologically suppressed on BIC/FTC/TAF (50 mg/200 mg/25 mg). In this trial, 513 adults with HIV-1 who had virologic suppression for three months or more on BIC/FTC/TAF, no history of treatment failure and no known resistance to DOR were randomized (2:1) and switched to DOR/ISL (n= 342) or continued treatment with BIC/FTC/TAF (n=171). The primary efficacy endpoint, the percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48 (non-inferiority margin 4%), was met, demonstrating non-inferiority to BIC/FTC/TAF; 1.5% of participants who switched to DOR/ISL had a viral load of ≥50 copies/mL at Week 48, compared to 0.6% on BIC/FTC/TAF (treatment difference 0.9%, 95% CI -1.9, 2.9). Results at Week 48 were recently published in The Lancet. At Week 96, DOR/ISL continued to demonstrate similar efficacy compared to BIC/FTC/TAF; 1.5% of participants on DOR/ISL had a viral load of ≥50 copies/mL compared to 1.2% of participants on BIC/FTC/TAF (treatment difference 0.3%, 95% CI -2.8, 2.4); 88.9% of participants on DOR/ISL maintained virologic suppression (HIV-1 RNA <50 copies/mL) compared to 90.1% of participants continuing BIC/FTC/TAF (treatment difference -1.2%, 95% CI -6.5, 5.0). No hypothesis testing was performed for these secondary endpoints. The safety profile for DOR/ISL at Week 96 continued to be similar to BIC/FTC/TAF with no new safety findings. No additional drug-related serious adverse events were reported in any group between Week 48 and Week 96. At Week 96, rates of discontinuation due to AEs were similar for both groups (3.2% vs. 2.9%). There were no differences between trial arms in CD4+ T-cell count or TLC changes through Week 96. About the Phase 3 data from MK-8591A-051 MK-8591A-051 is a Phase 3, open-label randomized, active-controlled, clinical trial to evaluate the efficacy and safety of a switch to investigational, once-daily DOR/ISL (100 mg/0.25 mg) in adults with HIV-1 infection that has been virologically suppressed using bART. In this trial, 551 adults with HIV-1 RNA <50 copies/mL for three months or more on oral 2- or 3-drug ART, with no history of treatment failure and no known virologic resistance to DOR, were randomized 2:1 and switched to DOR/ISL (n= 366) or continued bART (n=185), stratified by bART regimen. The primary efficacy endpoint, percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48 (non-inferiority margin 4%), was met, demonstrating DOR/ISL to be non-inferior to bART; 1.4% of participants who received DOR/ISL had a viral load of ≥50 copies/mL at Week 48, compared to 4.9% on bART (treatment difference -3.6%, 95% CI -7.8, -0.8). After Week 48 of the comparative portion of the study, all participants received open-label DOR/ISL through Week 144. Results at Week 48 were recently published in The Lancet. At Week 96, 1.9% of participants who continued on DOR/ISL for 96 weeks had HIV-1 RNA ≥50 copies/mL and 1.1% of participants who switched from bART to DOR/ISL at Week 48. Additionally, 92.6% of participants who were on DOR/ISL through 96 weeks and 96.6% of participants who switched to DOR/ISL at Week 48 maintained virologic suppression (HIV-1 RNA <50 copies/mL) at Week 96. At Week 96, there were similar rates of drug-related AEs between those who continued on DOR/ISL (13.7%) for 96 weeks and for those who switched from bART to DOR/ISL at Week 48 (11.3%) and rates of discontinuations due to AEs for those on DOR/ISL for 96 weeks (1.1%) and for those who switched from bART to DOR/ISL at Week 48 (0.6%) were similar. The mean percent change in total lymphocyte and CD4 counts were similar for participants who continued on DOR/ISL and switched from bART to DOR/ISL. No participants discontinued treatment due to decreased CD4+ T-cell count or TLC. About Islatravir (MK-8591) and Merck’s HIV Research Islatravir (MK-8591) is Merck’s investigational nucleoside analog that blocks HIV-1 replication by multiple mechanisms including inhibition of reverse transcriptase translocation, resulting in immediate chain termination and induction of structural changes in the viral DNA. Islatravir is under evaluation in multiple ongoing early and late-stage clinical trials in combination with other antiretrovirals for potential daily and once-weekly treatments for HIV-1, with islatravir serving as the anchor medicine in these two-drug regimens. Islatravir in combination with Gilead’s lenacapavir is in Phase 3 development as a novel oral once-weekly treatment for HIV-1 [ISLEND-1 (NCT06630286) and ISLEND-2 (NCT06630299)], and islatravir in combination with our company’s investigational non-nucleoside reverse transcriptase inhibitor (NNRTI) ulonivirine (MK-8507) is in Phase 2b development (MK-8591B-060, NCT06891066 and MK-8591B-062, NCT07266831) as an oral once-weekly treatment. MK-8527 is the company’s investigational, novel, once-monthly, oral candidate for pre-exposure prophylaxis (PrEP) for HIV-1. The Phase 3 EXPrESSIVE-11 (MK-8527-011, NCT07044297) trial is evaluating the safety and efficacy of MK-8527 as PrEP to reduce the risk of sexually acquired HIV-1 infection among people likely to be exposed to HIV-1 in 16 countries. The Phase 3 EXPrESSIVE-10 (MK-8527-010, NCT07071623) trial is evaluating the safety and efficacy of MK-8527 as PrEP to reduce the risk of sexually acquired HIV-1 infection among women and adolescent girls in sub-Saharan Africa. Both trials are now enrolling. For an overview of Merck’s HIV treatment and prevention clinical development program, please click here. Indications and usage for PIFELTRO® (doravirine) and DELSTRIGO® (doravirine, lamivudine, and tenofovir disoproxil fumarate) in the U.S. PIFELTRO is indicated in combination with other antiretroviral (ARV) agents for the treatment of HIV-1 infection in adult patients with no prior ARV treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable ARV regimen with no history of treatment failure and no known substitutions associated with resistance to doravirine. DELSTRIGO is indicated as a complete regimen for the treatment of HIV-1 infection in adult patients with no prior ARV treatment history or to replace the current ARV regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable ARV regimen with no history of treatment failure and no known substitutions associated with resistance to the individual components of DELSTRIGO. Selected Safety Information Warning: Posttreatment Acute Exacerbation of Hepatitis B Virus (HBV) for DELSTRIGO All patients with HIV-1 should be tested for the presence of HBV before initiating ARV therapy. Severe acute exacerbations of HBV have been reported in people with concomitant HIV-1 and HBV who have discontinued products containing lamivudine or tenofovir disoproxil fumarate (TDF), which are components of DELSTRIGO. Patients coinfected with HIV-1 and HBV who discontinue DELSTRIGO should be monitored with both clinical and laboratory follow-up for at least several months after stopping DELSTRIGO. If appropriate, initiation of anti-HBV therapy may be warranted. Contraindications PIFELTRO and DELSTRIGO are contraindicated when coadministered with drugs that are strong cytochrome P450 (CYP)3A enzyme inducers (including the anticonvulsants carbamazepine, oxcarbazepine, phenobarbital, and phenytoin; the androgen receptor inhibitor enzalutamide; the antimycobacterials rifampin and rifapentine; the cytotoxic agent mitotane; and the herbal product St. John’s wort (Hypericum perforatum)), as significant decreases in doravirine plasma concentrations may occur, which may decrease the effectiveness of DELSTRIGO and PIFELTRO. DELSTRIGO is contraindicated in patients with a previous hypersensitivity reaction to lamivudine. Warnings and Precautions Severe Skin Reactions Severe skin reactions, including Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), have been reported during the postmarketing experience with doravirine-containing regimens. Discontinue PIFELTRO or DELSTRIGO, and other medications known to be associated with severe skin reactions, immediately if a painful rash with mucosal involvement or a progressive severe rash develops. Clinical status should be closely monitored, and appropriate therapy should be initiated. New or Worsening Renal Impairment Renal impairment, including cases of acute renal failure and Fanconi syndrome, have been reported with the use of TDF. DELSTRIGO should be avoided with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple NSAIDs). Cases of acute renal failure after initiation of high-dose or multiple NSAIDs have been reported in people living with HIV with risk factors for renal dysfunction who appeared stable on TDF. Prior to or when initiating DELSTRIGO, and during treatment, assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients. In patients with chronic kidney disease, also assess serum phosphorus. Discontinue DELSTRIGO in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome. Discontinue DELSTRIGO if estimated creatinine clearance declines below 50 mL/min. Bone Loss and Mineralization Defects In clinical trials in adults living with HIV, TDF was associated with slightly greater decreases in bone mineral density (BMD) and increases in biochemical markers of bone metabolism. Serum parathyroid hormone levels and 1,25 Vitamin D levels were also higher. Cases of osteomalacia associated with proximal renal tubulopathy have been reported with the use of TDF. The effects of TDF-associated changes in BMD and biochemical markers on long-term bone health and future fracture risk in adults are unknown. Immune Reconstitution Syndrome Immune reconstitution syndrome can occur, including the occurrence of autoimmune disorders with variable time to onset, which may necessitate further evaluation and treatment. Drug Interactions Because DELSTRIGO is a complete regimen, coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended. Coadministration of PIFELTRO with efavirenz, etravirine, or nevirapine is not recommended. If DELSTRIGO is coadministered with rifabutin, take one tablet of DELSTRIGO once daily, followed by one tablet of doravirine (PIFELTRO) approximately 12 hours after the dose of DELSTRIGO. If PIFELTRO is coadministered with rifabutin, increase PIFELTRO dosage to one tablet twice daily (approximately 12 hours apart). Consult the full Prescribing Information prior to and during treatment for more information on potential drug-drug interactions. Dosage and Administration/Specific Populations Renal Impairment Because DELSTRIGO is a fixed-dose combination tablet and the dosage of lamivudine and TDF cannot be adjusted, DELSTRIGO is not recommended in patients with estimated creatinine clearance less than 50 mL/min. Adverse Reactions The most common adverse reactions with DELSTRIGO (incidence ≥5%, all intensities) were dizziness (7%), nausea (5%), and abnormal dreams (5%). The most common adverse reactions with PIFELTRO (incidence ≥5%, all intensities) were nausea (7%), dizziness (7%), headache (6%), fatigue (6%), diarrhea (6%), abdominal pain (5%), and abnormal dreams (5%). By week 96 in DRIVE-FORWARD, 2% of adult participants in the PIFELTRO group and 3% in the darunavir+ritonavir (DRV+r) group had adverse events leading to discontinuation of study medication. By week 96 in DRIVE-AHEAD, 3% of adult participants in the DELSTRIGO group and 7% in the efavirenz (EFV)/emtricitabine (FTC)/TDF group had adverse events leading to discontinuation of study medication. In DRIVE-FORWARD, mean changes from baseline at week 48 in LDL-cholesterol (LDL-C) and non-HDL-cholesterol (non-HDL-C) were pre-specified. LDL-C: -4.6 mg/dL in the PIFELTRO group vs 9.5 mg/dL in the DRV+r group. Non-HDL-C: -5.4 mg/dL in the PIFELTRO group vs 13.7 mg/dL in the DRV+r group. The clinical benefits of these findings have not been demonstrated. In DRIVE-AHEAD, mean changes from baseline at week 48 in LDL-C and non-HDL-C were pre-specified. LDL-C: -2.1 mg/dL in the DELSTRIGO group vs 8.3 mg/dL in the EFV/FTC/TDF group. Non-HDL-C: -4.1 mg/dL in the DELSTRIGO group vs 12.7 mg/dL in the EFV/FTC/TDF group. The clinical benefits of these findings have not been demonstrated. In DRIVE-SHIFT, mean changes from baseline at week 24 in LDL-C and non-HDL-C were pre-specified. LDL-C: -16.3 mg/dL in the DELSTRIGO group vs -2.6 mg/dL in the PI + ritonavir group. Non-HDL-C: -24.8 mg/dL in the DELSTRIGO group vs -2.1 mg/dL in the PI + ritonavir group. The clinical benefits of these findings have not been demonstrated. In DRIVE-AHEAD, neuropsychiatric adverse events were reported in the three pre-specified categories of sleep disorders and disturbances, dizziness, and altered sensorium. Twelve percent of adult participants in the DELSTRIGO group and 26% in the EFV/FTC/TDF group reported neuropsychiatric adverse events of sleep disorders and disturbances; 9% in the DELSTRIGO group and 37% in the EFV/FTC/TDF group reported dizziness; and 4% in the DELSTRIGO group and 8% in the EFV/FTC/TDF group reported altered sensorium. The safety of DELSTRIGO in virologically suppressed adults was based on week 48 data from participants in the DRIVE-SHIFT trial. Overall, the safety profile in virologically suppressed adult participants was similar to that in participants with no ARV treatment history. Serum ALT and AST Elevations: In the DRIVE-SHIFT trial, 22% and 16% of participants in the immediate switch group experienced ALT and AST elevations greater than 1.25 X ULN, respectively, through 48 weeks on DELSTRIGO. For these ALT and AST elevations, no apparent patterns with regard to time to onset relative to switch were observed. One percent of participants had ALT or AST elevations greater than 5 X ULN through 48 weeks on DELSTRIGO. The ALT and AST elevations were generally asymptomatic, and not associated with bilirubin elevations. In comparison, 4% and 4% of participants in the delayed switch group experienced ALT and AST elevations of greater than 1.25 X ULN through 24 weeks on their baseline regimen. Pregnancy/Breastfeeding There is a pregnancy exposure registry that monitors pregnancy outcomes in individuals exposed to PIFELTRO or DELSTRIGO during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263. Inform individuals with HIV-1 infection of the potential risks of breastfeeding, including: (1) HIV-1 transmission (in HIV-1–negative infants), (2) developing viral resistance (in HIV-1–positive infants), and (3) serious adverse reactions in a breastfed infant similar to those seen in adults. Merck’s Commitment to HIV For 40 years, Merck has been committed to scientific research and discovery in HIV leading to scientific breakthroughs that have helped change HIV treatment. Our work has been pioneering in the development of new options across multiple drug classes to help those impacted by HIV. Today, we are developing a series of antiviral options designed to help people manage HIV and protect people from HIV. We are researching for real life and want to ensure people are not defined by HIV. Our work focuses on transformational innovations, collaborations with others in the global HIV community, and access initiatives aimed at the goal of helping to end the HIV epidemic for everyone. About Merck At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit www.merck.com and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn. Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA This news release of Merck & Co., Inc., Rahway, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions. The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s Annual Report on Form 10-K for the year ended December 31, 2025 and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov). Please see Prescribing Information for PIFELTRO (doravirine) at: https://www.merck.com/product/usa/pi_circulars/p/pifeltro/pifeltro_pi.pdf and Patient Information for PIFELTRO at: https://www.merck.com/product/usa/pi_circulars/p/pifeltro/pifeltro_ppi.pdf Please see Prescribing Information for DELSTRIGO (doravirine, lamivudine, and tenofovir disoproxil fumarate) at: https://www.merck.com/product/usa/pi_circulars/d/delstrigo/delstrigo_pi.pdf and Patient Information for DELSTRIGO at: https://www.merck.com/product/usa/pi_circulars/d/delstrigo/delstrigo_ppi.pdf _______________________ ibictegravir/emtricitabine/tenofovir alafenamide (BIKTARVY) is a registered trademark of Gilead Sciences, Inc. Media Contacts: Eilyn Segura (203) 940-6259 Deb Wambold (215) 779-2234 Investor Contacts: Peter Dannenbaum (732) 594-1579 Damini Chokshi (732) 594-1577

Record total revenues of $211.6 million and $719.0 million in the fourth quarter and full year 2025, a 21% and 9% increase compared to same periods last year. Combined revenues of the Company's four growth products increased to $161.3 million and $521.8 million in the fourth quarter and full year 2025, representing year-over-year growth of 45% and 40% respectively. The strong growth in both periods was driven by an increase in net sales of Qelbree® and GOCOVRI®, and the addition of sales from ZURZUVAE® and ONAPGO™. Cash, cash equivalents and current marketable securities were $308.7 million at December 31, 2025 . New patient initiation for ONAPGO resumed in the first quarter of 2026. Full year 2026 guidance for total revenues of $840 million to $870 million , operating earnings of $0 million to $30 million , and adjusted operating earnings (Non-GAAP)(1) of $140 million to $170 million . ROCKVILLE, Md. , Feb. 24, 2026 (GLOBE NEWSWIRE) -- Supernus Pharmaceuticals, Inc. (Nasdaq: SUPN), a biopharmaceutical company focused on developing and commercializing products for the treatment of central nervous system (CNS) diseases, today announced financial results for the fourth quarter and full year 2025 and associated Company developments. "We made significant progress in 2025 against our strategic objectives, with record total revenues, including strong growth in combined revenues of our growth products, the successful acquisition of Sage Therapeutics, Inc. , and the U.S. Food and Drug Administration's approval and launch of ONAPGO for Parkinson's disease," said Jack Khattar , President and CEO of Supernus. "In 2026, we are focused on continued progress of our key growth products, including resumption of new patient initiation for ONAPGO, while advancing our pipeline of promising therapeutic candidates." Commercial Highlights The Company has made progress securing additional product supply of ONAPGO from the current supplier and as a result has resumed new patient initiation. In addition, the Company is working with a second supplier, which is expected to begin supplying ONAPGO in 2027. ONAPGO net product sales were $8.9 million in the fourth quarter of 2025 following the U.S. commercial launch in April 2025 . Since launch, more than 1,800 enrollment forms have been submitted by over 540 prescribers. Collaboration revenue from ZURZUVAE was $32.8 million in the fourth quarter of 2025. Collaboration revenue (ZURZUVAE) represents 50% of the net revenues for ZURZUVAE recorded by Biogen Inc. Fourth quarter 2025 U.S sales of ZURZUVAE, as reported by Biogen Inc., increased approximately 187% compared to the same period in 2024 and approximately 19% compared to the third quarter of 2025. The total number of prescriptions for ZURZUVAE increased by more than 150% in 2025 compared to 2024. Net sales of Qelbree increased 9% to $81.0 million in the fourth quarter of 2025, compared to the same period in 2024, driven primarily by volume growth and partially offset by an annual gross-to-net deduction that was reflected in fourth quarter 2025. Total IQVIA prescriptions(5) for Qelbree were 253,742 for the fourth quarter 2025, representing an increase of 18% compared to the same period in the prior year. Net sales of GOCOVRI increased 5% to $38.6 million in the fourth quarter of 2025, compared to the same period in 2024. Total number of prescriptions grew by 14% in 2025 compared to 2024. Product Pipeline Update SPN-817 – Novel first-in-class highly selective AChE inhibitor for epilepsy The Phase 2b randomized, double-blind, placebo-controlled study of 3mg and 4mg twice daily doses is ongoing with a targeted enrollment of approximately 258 adult patients with treatment resistant focal seizures. SPN-820 – Novel first-in-class molecule that increases mTORC1 mediated synaptic function for depression The Company initiated a follow-on Phase 2b multi-center, randomized, double-blind, placebo-controlled trial in approximately 200 adults with major depressive disorder (MDD). The study will examine the safety and tolerability of SPN-820 2400 mg given intermittently (twice weekly) as an adjunctive treatment to the current baseline antidepressant therapy, as well as assess the rapid onset of improvement in depressive symptoms. SPN-443 – Novel stimulant for attention-deficit/hyperactivity disorder (ADHD) The Company expects to initiate a Phase 1 single-ascending/multiple-ascending dose study in adult healthy volunteers in the second half of 2026. Financial Highlights This section includes information on non-GAAP financial measures. See "Non-GAAP Financial Information" section for information on non-GAAP financial measures. In addition, a reconciliation of applicable GAAP to non-GAAP financial information is included at the end of this press release. Revenues The following table provides information regarding total revenues (dollars in millions): Other Financial Highlights The Company recognized $15.0 million of licensing revenue in the fourth quarter of 2025 related to the achievement of a regulatory milestone under its collaboration agreement with Shionogi. Operating loss was $4.0 million and $62.3 million for the three and twelve months ended December 31, 2025 , compared to operating earnings of $21.4 million and $81.7 million for the same periods in 2024. The change in both periods was primarily due to higher selling, general and administrative expenses, including approximately $72.9 million of acquisition-related costs associated with the Sage acquisition reported in 2025, change in contingent consideration loss (gain), and incremental intangible asset amortization expense for ZURZUVAE and ONAPGO intangible assets in 2025, partially offset by higher revenues. Adjusted operating earnings (non-GAAP)(1) were $48.5 million and $158.7 million for the three and twelve months ended December 31, 2025 , compared to $48.3 million and $183.7 million for the same periods in 2024. Net loss and diluted loss per share were $4.1 million and $0.07 for the three months ended December 31, 2025 , and $38.6 million and $0.68 for the twelve months December 31, 2025 , respectively, compared to net earnings and diluted earnings per share of $15.3 million and $0.27 for the three months ended December 31, 2024 , and $73.9 million and $1.32 for the twelve months December 31, 2024 , respectively. Cash, cash equivalents, and current marketable securities were approximately $308.7 million as of December 31, 2025 , compared to $453.6 million as of December 31, 2024 . This decrease was primarily due to the funding of the Sage acquisition, partially offset by cash generated from operations. Full Year 2026 Financial Guidance The Company expects to achieve the following financial objectives in 2026 (dollars in millions): Non-GAAP Financial Information This press release contains financial measures that present financial information which do not comply with United States generally accepted accounting principles (GAAP). The non-GAAP financial measures should be considered in addition to, not as a substitute for or in isolation from, or superior to measures prepared in accordance with GAAP. Non-GAAP adjusted operating earnings on a historical and projected basis adjusts for non-cash share-based compensation expense, depreciation and amortization, intangible asset impairment charges and changes to fair value of contingent consideration, and for factors that are unusual, non-recurring or unpredictable, and excludes those costs, expenses, and other specified items presented in the reconciliation tables in this press release. In addition to non-GAAP adjusted operating earnings, we also present total revenues excluding net sales of Trokendi XR (GAAP) and Oxtellar XR (GAAP), which is a non-GAAP measure and is calculated as total revenues (GAAP) less net product sales of Trokendi XR (GAAP) and Oxtellar XR (GAAP). Beginning in the year a product loses exclusivity due to generic entrants, we generally do not expect net product sales of such products to constitute a significant part of our revenue in the future. We believe that the use of non-GAAP financial measures provides useful supplemental information to management, investors, analysts and others regarding the Company's revenue and results of operations and assist management, investors, analysts, and others in understanding and evaluating our revenue growth and the performance of the business. There are limitations associated with the use of non-GAAP financial measures and therefore comparability may be limited. These limitations include: non-GAAP financial measures that may not be entirely comparable to similarly titled measures used by other companies; these may not reflect all items of income and expense, as applicable, that affect our operations; there may be potential differences among calculation methodologies; these may differ from the non-GAAP information used by other companies, including peer companies. We mitigate these limitations by reconciling the non-GAAP financial measure to the most comparable GAAP financial measure. Investors are encouraged to review the reconciliation. The Company's 2026 financial guidance is also being provided on both a GAAP and a non-GAAP basis. Conference Call Details Supernus will host a conference call and webcast today, February 24, 2026 , at 4:30 p.m. Eastern Time to discuss these results. A live webcast will be available in the Events & Presentations section of the Company's Investor Relations website www.supernus.com/investors. Participants may also pre-register any time before the call here. Once registration is completed, participants will be provided a dial-in number with a personalized conference code to access the call. Please dial in 15 minutes prior to the start time. Following the live call, a replay will be available on the Company's Investor Relations website www.supernus.com/investors. The webcast will be available on the Company's website for 60 days following the live call. About Supernus Pharmaceuticals, Inc. Supernus Pharmaceuticals is a biopharmaceutical company focused on developing and commercializing products for the treatment of central nervous system (CNS) diseases. Our diverse neuroscience portfolio includes approved treatments for attention-deficit hyperactivity disorder (ADHD), dyskinesia in Parkinson's disease (PD) patients receiving levodopa-based therapy, hypomobility in PD, postpartum depression (PPD), epilepsy, migraine, cervical dystonia, and chronic sialorrhea. We are developing a broad range of novel product candidates for CNS disorders. For more information, please visit www.supernus.com. Forward-Looking Statements This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements do not convey historical information but relate to predicted or potential future events that are based upon management's current expectations. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. In addition to the factors mentioned in this press release, such risks and uncertainties include, but are not limited to, the Company's ability to sustain and increase its profitability; the Company's ability to raise sufficient capital to fully implement its corporate strategy; the implementation of the Company's corporate strategy; the Company's future financial performance and projected expenditures; the Company's ability to increase the number of prescriptions written for each of its products, and the products of its subsidiaries; the Company's ability to increase its net revenue from its products, and the products of its subsidiaries; the Company's ability to commercialize its products, and the products of its subsidiaries; the Company's ability to enter into future collaborations with pharmaceutical companies and academic institutions or to obtain funding from government agencies; the Company's product research and development activities, including the timing and progress of the Company's clinical trials, and projected expenditures; the Company's ability to receive, and the timing of any receipt of, regulatory approvals to develop and commercialize the Company's product candidates; the Company's ability to protect its intellectual property and the intellectual property of its subsidiaries and operate its business without infringing upon the intellectual property rights of others; the Company's expectations regarding federal, state and foreign regulatory requirements; the therapeutic benefits, effectiveness and safety of the Company's product candidates; the accuracy of the Company's estimates of the size and characteristics of the markets that may be addressed by its product candidates; the Company's ability to increase its manufacturing capabilities for its products and product candidates; the Company's projected markets and growth in markets; the Company's product formulations and patient needs and potential funding sources; the Company's staffing needs; changes to laws and regulations applicable to our industry, the impact of macroeconomic factors, such as economic downturns or uncertainty, international conflict, trade disputes and tariffs; and other risk factors set forth from time to time in the Company's filings with the Securities and Exchange Commission made pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934, as amended. The Company undertakes no obligation to update the information in this press release to reflect events or circumstances after the date hereof or to reflect the occurrence of anticipated or unanticipated events. Supernus Pharmaceuticals, Inc. Reconciliations of GAAP to Non-GAAP Financial Information(unaudited) Reconciliation of GAAP Total revenues to Non-GAAP Total revenues excluding Trokendi XR and Oxtellar XR net sales An itemized reconciliation between total revenues on a GAAP basis and Total revenues excluding Trokendi XR and Oxtellar XR net sales, a non-GAAP measure, is as follows (dollars in millions): Reconciliation of GAAP Operating Earnings (Loss) to Non-GAAP Adjusted Operating Earnings An itemized reconciliation between operating earnings (loss) on a GAAP basis and adjusted operating earnings on a non-GAAP basis is as follows (dollars in millions): Non-GAAP adjusted operating earnings adjusts for one-time acquisition related costs and non-cash items, which include amortization of intangible assets, share-based compensation expense, change in fair value of contingent consideration, and depreciation. Reconciliation of Full Year 2026 Financial Guidance – GAAP Operating Earnings to Non-GAAP Adjusted Operating Earnings An itemized reconciliation between projected operating earnings on a GAAP basis for the full year 2026 and projected adjusted operating earnings on a non-GAAP basis for the full year 2026 is as follows (dollars in millions): CONTACTS: Jack A. Khattar , President and CEO Timothy C. Dec , Senior Vice President and CFO Supernus Pharmaceuticals, Inc. (301) 838-2591 or INVESTOR CONTACT: Peter Vozzo ICR Healthcare (443) 213-0505peter.vozzo@icrhealthcare.com Source: Supernus Pharmaceuticals, Inc.