Ralinepag cuts PAH clinical worsening by 55% in UTHR (NASDAQ: UTHR) phase 3 trial
Rhea-AI Filing Summary
United Therapeutics reported that its pivotal phase 3 ADVANCE OUTCOMES study of ralinepag in pulmonary arterial hypertension met its primary goal. Ralinepag reduced the risk of a clinical worsening event by 55% versus placebo and increased the odds of clinical improvement by 47% through Week 28.
The once-daily oral prostacyclin showed statistically significant benefits on six-minute walk distance and NT-proBNP, with no new safety signals observed. The company plans to submit a New Drug Application for ralinepag to the FDA by the second half of 2026 and is hosting a webcast to discuss the results.
Positive
- Pivotal phase 3 success in PAH: Ralinepag reduced the risk of clinical worsening by 55% versus placebo and improved multiple secondary endpoints, strengthening its profile as a potential once-daily oral prostacyclin therapy.
- Clear regulatory path outlined: United Therapeutics plans to submit a New Drug Application for ralinepag to the FDA by the second half of 2026, moving the program toward potential commercialization.
Negative
- None.
Insights
Pivotal PAH trial hits strong efficacy endpoints, supporting an FDA filing for ralinepag.
The ADVANCE OUTCOMES phase 3 study showed ralinepag cut the risk of clinical worsening by
Secondary measures, including six-minute walk distance, NT-proBNP, and odds of clinical improvement (up
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Item 7.01. Regulation FD Disclosure
On March 2, 2026, United Therapeutics Corporation (the “Company”) issued a press release announcing positive results of the ADVANCE OUTCOMES clinical study of ralinepag in patients with pulmonary arterial hypertension. The press release is attached as Exhibits 99.1 and is incorporated herein by reference.
As disclosed in the press release, the Company intends to host a webcast presentation to discuss the ADVANCE OUTCOMES results at 8:30 a.m. Eastern Time on March 2, 2026. The presentation will include the slides furnished as Exhibit 99.2 hereto and incorporated herein by reference. These slides will also be posted to the Company’s website at https://ir.unither.com/events-and-presentations. A rebroadcast of the webcast will be available for one year and can be accessed at the same location.
Item 9.01. Exhibits
| (d) Exhibits | |||
| Exhibit No. | Description of Exhibit | ||
| 99.1 | Press Presentation dated March 2, 2026 | ||
| 99.2 | Investor Presentation dated March 2, 2026 | ||
| 104 | The cover page from this Current Report on Form 8-K, formatted in Inline XBRL | ||
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SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| UNITED THERAPEUTICS CORPORATION | ||
| Dated: March 2, 2026 | By: | /s/ Paul A. Mahon |
| Name: | Paul A. Mahon | |
| Title: | General Counsel | |
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Exhibit 99.1
United Therapeutics Corporation Announces Ralinepag Achieved 55% Reduction in Risk of Clinical Worsening in Pivotal Pulmonary Arterial Hypertension Study, Delivering Exceptional, Highly Statistically Significant Efficacy
The phase 3 ADVANCE OUTCOMES study of ralinepag met its primary endpoint and several important secondary endpoints, including increasing odds of clinical improvement by 47%, in predominantly pre-treated patients with pulmonary arterial hypertension (PAH)
Ralinepag has the potential to redefine the PAH treatment landscape as the first and only once-daily oral prostacyclin, combining potent receptor affinity with continuous exposure to deliver long-term, durable efficacy and disease-mitigating outcomes
United Therapeutics intends to submit a New Drug Application (NDA) for ralinepag to the U.S. Food and Drug Administration (FDA) by the second half of 2026
United Therapeutics will host a webcast at 8:30 a.m. Eastern Time today to further discuss the study results
SILVER SPRING, Md. and RESEARCH TRIANGLE PARK, N.C., March 2, 2026 — United Therapeutics Corporation (Nasdaq: UTHR), a public benefit corporation, today announced that its long-term pivotal phase 3 ADVANCE OUTCOMES study met its primary endpoint, with ralinepag reducing the risk of a clinical worsening event by 55% compared with placebo in patients with PAH (hazard ratio 0.45, 95% CI [0.33-0.62]; p<0.0001).
Ralinepag demonstrated durable efficacy in delaying disease progression during the study, in which 80% of patients were on dual background therapy and 70% of patients were considered World Health Organization (WHO)/New York Heart Association (NYHA) Functional Class (FC) II at baseline.
Statistically significant improvements relative to placebo were also observed in important secondary endpoints, including six-minute walk distance (6MWD) and change in N-terminal pro-B-type natriuretic peptide (NT-proBNP), with ralinepag increasing the odds of achieving clinical improvement by 47% from baseline to Week 28 (p=0.015).
Benefits were consistent across all patient subgroups, including time since diagnosis, disease etiology, baseline 6MWD, and use of background therapies, reinforcing the robustness of the treatment effect and the potential broad therapeutic relevance of ralinepag.
Treatment with ralinepag was well-tolerated and the safety profile was consistent with known prostacyclin-related adverse events. No new safety signals were observed.
“PAH is a progressive, life-threatening disease that has a devastating impact on patients’ lives. In the ADVANCE OUTCOMES study, ralinepag delayed disease progression in patients with PAH facing significant disease burden at baseline. Ralinepag’s potency and once-daily oral dosing make these outcomes highly relevant in real-world settings,” said Vallerie V. McLaughlin, M.D., Kim A. Eagle MD Endowed Professor of Cardiovascular Medicine and Director, Pulmonary Hypertension Program at University of Michigan and Chair of the ADVANCE OUTCOMES Steering Committee.*
“United Therapeutics was founded on the idea that we could bring transformative therapies to people living with PAH. Our achievement in this pivotal trial is among the most important in our history and strengthens our decades-long commitment to advancing prostacyclin-based science. The strength and consistency of these findings give us great optimism that ralinepag could meaningfully improve long-term outcomes and, if approved, usher in a new era of treatment for PAH that brings us closer than ever to addressing the profound unmet needs that persist in this disease. We are grateful for the essential contributions of the study participants and the investigators whose work underpinned this tremendous result,” said Martine Rothblatt, Ph.D., Chairperson and Chief Executive Officer of United Therapeutics.
* Dr. McLaughlin has received compensation as a consultant of United Therapeutics.
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“These results mark a significant advancement for PAH patients. With its extended-release profile and pharmacokinetic characteristics that mimic the steady-state exposure of parenteral therapy, ralinepag provides disease-mitigating capabilities that target underlying PAH pathology and achieve impressive clinical benefits,” said Derek Solum, Ph.D., Senior Director, Product Development at United Therapeutics and the lead for the global ADVANCE OUTCOMES program.
United Therapeutics intends to present full results from the ADVANCE OUTCOMES study at an upcoming international conference and to submit an NDA for ralinepag to the FDA by the second half of 2026.
United Therapeutics will host a public webcast today, March 2, 2026, at 8:30 a.m. Eastern Time. The webcast will be accessible via United Therapeutics’ website at https://ir.unither.com/events-and-presentations. A rebroadcast of the webcast will be available for one year and can be accessed at the same location.
About Ralinepag
Ralinepag is a highly selective and potent prostacyclin (IP) receptor agonist with multiple pathway effects, including vasodilatory, anti-proliferative, and anti-inflammatory effects.1,2 It demonstrates six-fold higher binding affinity for the IP receptor than MRE-269 (selexipag’s active metabolite) and achieves sustained IP receptor occupancy similar to parenteral therapy.3-6 Ralinepag helps to restore prostacyclin signaling and activates IP receptors on pulmonary artery endothelial and smooth muscle cells to trigger the downstream conversion of ATP to cAMP.1,7 Ralinepag is six- to eight-fold more potent at increasing in vitro cAMP levels compared with the active metabolite of selexipag.5 Elevated intracellular cAMP acts on pathways implicated in PAH progression by promoting vasodilation and inhibiting vascular remodeling, suggesting potential for vascular protection.1,5,7 In a phase 2 study, ralinepag significantly reduced pulmonary vascular resistance compared with placebo in PAH patients on mono (41%) or dual combination (59%) background therapy.8
About ADVANCE OUTCOMES
ADVANCE OUTCOMES was a pivotal phase 3 multicenter, global, randomized, double-blind, placebo-controlled, event-driven study to evaluate the efficacy and safety of ralinepag in 687 patients with PAH. Patients who completed the study had the option to enroll in an ongoing open-label extension study, ADVANCE EXTENSION.
In this event-driven study, patients were randomly assigned (1:1) to receive ralinepag or placebo, in addition to their standard of care PAH-specific background therapy. Once-daily dosing was individualized and titrated based on tolerability and clinical response. No dose ceiling was specified.
The primary endpoint was time to first adjudicated clinical worsening event, defined as death, nonelective hospital admission for worsening PAH, initiation of parenteral or inhaled prostacyclin pathway agent for treatment of worsening PAH, disease progression, or unsatisfactory long-term clinical response.
Secondary endpoints included changes from Baseline to Week 28 in NT-proBNP, 6MWD, and WHO/NYHA FC; shift and proportion of patients with improved risk status, clinical improvement, health-related quality of life (SF-36) as measured by patient-reported outcomes; time to first all-cause nonelective hospitalization; time to all-cause mortality; heart rate recovery following completion of the 6MWT; and safety and tolerability.
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About PAH
PAH is a life-threatening disease that affects the blood vessels in the lungs and is characterized by increased pressure in the pulmonary arteries, which are the blood vessels leading from the heart to the lungs. The elevated pressure in the pulmonary arteries strains the right side of the heart as it pumps blood to the lungs. This eventually leads to right heart failure and, ultimately, death. PAH is characterized by structural changes in blood vessel walls, aggregation of platelets, and alteration of smooth muscle cell function. PAH affects about 500,000 individuals worldwide, with around 50,000 people affected in the United States. Increases in the number of people diagnosed with the disease have been observed, but due to the rarity of the disease and the complexity of diagnosing it, only a small fraction of patients with PAH are treated.
About United Therapeutics
Founded by CEO Martine Rothblatt to discover a cure for her daughter's life-threatening rare disease, pulmonary arterial hypertension, United Therapeutics transforms the treatment of rare diseases and pioneers alternatives to expand the supply of transplantable organs. From our innovative therapies to our groundbreaking manufactured organs, we are bold and unconventional. We move quickly from scientific theory to practical technologies that can save lives. As a public benefit corporation, even our legal structure reflects our commitments. We serve patients, act with integrity, create long-term shareholder value, and operate with sustainable practices that protect the future we are working to build. Visit us at www.unither.com and follow us on LinkedIn, Facebook, and Instagram.
Forward-Looking Statements
Statements included in this press release that are not historical in nature are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include, among others, the potential timing and outcome of our efforts to seek FDA approval of ralinepag, including our plan to submit an NDA to the FDA by the second half of 2026; the potential impacts of ralinepag on PAH treatment, including the potential for ralinepag to redefine the PAH treatment landscape; the potential for ralinepag to become the first and only once-daily oral prostacyclin; the potential for ralinepag to deliver long-term, durable efficacy and disease-mitigating outcomes; the potential for ralinepag to meaningfully improve long-term outcomes and usher in a new era of treatment for PAH, bring us closer than ever to addressing unmet needs that persist for PAH patients; our commitment to advancing prostacyclin-based science; and our goals of expanding the supply of transplantable organs, developing practical technologies that can save lives, creating long-term shareholder value, and operating with sustainable practices. These forward-looking statements are subject to certain risks and uncertainties, such as those described in our periodic reports filed with the Securities and Exchange Commission, that could cause actual results to differ materially from anticipated results. Consequently, such forward-looking statements are qualified by the cautionary statements, cautionary language, and risk factors set forth in our periodic reports and documents filed with the Securities and Exchange Commission, including our most recent Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and Current Reports on Form 8-K. We claim the protection of the safe harbor contained in the Private Securities Litigation Reform Act of 1995 for forward-looking statements. We are providing this information as of March 2, 2026, and assume no obligation to update or revise the information contained in this press release whether as a result of new information, future events or any other reason.
For Further Information Contact:
Investor Inquiries
https://ir.unither.com/contact-ir
Media Inquiries
communications@unither.com
References
| 1. | Clapp LH, Abu-Hanna JHJ, Patel JA. Diverse pharmacology of prostacyclin mimetics: implications for pulmonary hypertension. In: Nakanishi T, Baldwin HS, Fineman JR, Yamagishi H, eds. Molecular Mechanism of Congenital Heart Disease and Pulmonary Hypertension. Springer; 2020:31-61. |
| 2. | Stitham J, Arehart E, Gleim SR, Hwa J. Prostacyclin: an inflammatory paradox. Front Pharmacol. 2011;2:24. |
| 3. | Asaki T, Kuwano K, Morrison K, Gatfield J, Hamamoto T, Clozel M. Selexipag: An Oral and Selective IP Prostacyclin Receptor Agonist for the Treatment of Pulmonary Arterial Hypertension. J Med Chem. 2015;58(18):7128-7137. |
| 4. | Tran JQ, Hartung J, Feurer A, et al. Discovery of 2-(((1r,4r)-4-(((4-Chlorophenyl)(phenyl)carbamoyl)oxy)methyl)cyclohexyl)methoxy) acetate (Ralinepag): An Orally Active Prostacyclin Receptor Agonist for the Treatment of Pulmonary Arterial Hypertension. J Med Chem. 2017;60(21):8829-8846. |
| 5. | Ataya A, Coons JC, Patzlaff N, et al. Safety and pharmacokinetics of ralinepag, a novel oral prostacyclin receptor agonist. JHLT Open. 2025;9:100270. |
| 6. | Grundy JS, King CD, Adams JW, Cabell CH. Safety, tolerability, and pharmacokinetics of the selective prostacyclin receptor agonist ralinepag in single and multiple dosing studies of an immediate-release oral formulation in healthy volunteers. Pulm Circ. 2020;10(2):2045894020922814. |
| 7. | Abu-Hanna J, Patel JA, Denton CP, Clapp LH. Prostacyclin mimetics inhibit DRP1-mediated pro-proliferative mitochondrial fragmentation in pulmonary arterial hypertension. Vasc Pharmacol. 2023;151:107194. |
| 8. | Torres F, Farber H, Ristic A, et al. Efficacy and safety of ralinepag, a novel oral IP agonist, in PAH patients on mono or dual background therapy: results from a phase 2 randomised, parallel group, placebo-controlled trial. Eur Respir J. 2019;54(4):1901030. |
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Exhibit 99.2
| United Therapeutics Corporation Phase 3 ADVANCE OUTCOMES Results Webcast MARCH 2, 2026 Exhibit 99.2 |
| 2 INTRODUCTION Safe Harbor Statement MIROKIDNEY, MIROLIVER, MIROLIVERELAP, ORENITRAM, REMODULIN, TYVASO, TYVASO DPI, and UNITUXIN are registered trademarks of United Therapeutics Corporation and/or its subsidiaries. UHEART, UKIDNEY, ULOBE, ULUNG, UTHYMOKIDNEY, and REMUNITYPRO are trademarks of United Therapeutics Corporation and/or its subsidiaries. ADCIRCA is a registered trademark of Eli Lilly and Company. 2 All statements in this presentation are made as of March 2, 2026. We undertake no obligation to publicly update or revise these statements, whether as a result of new information, future events, or otherwise. Statements included in this presentation that are not historical in nature are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include, among others, statements related to our revenue growth expectations, the timing and success of our pipeline programs, our planned manufacturing and field force expansions, our organ manufacturing efforts, and similar statements concerning anticipated future events and expectations. We caution you that these statements are not guarantees of future performance and are subject to numerous evolving risks and uncertainties that we may not be able to accurately predict or assess, including the risk factors that we describe in our Securities and Exchange Commission filings, including our most recent Annual Report on Form 10-K or Quarterly Report on Form 10-Q. Any of these factors could cause actual results to differ materially from the expectations we express or imply in this presentation. This presentation and any related discussions or statements are intended to educate investors about our company. Sometimes that process includes reporting on the progress and results of clinical trials or other developments with respect to our products. This presentation and any related discussions or statements are not intended to promote our products, to suggest that our products are safe and effective for any use other than what is consistent with their FDA-approved labeling, or to provide all available information regarding the products, their risks, or related clinical trial results. Anyone seeking information regarding the use of one of our products should consult the full prescribing information for the product available on our website at www.unither.com. |
| 3 INTRODUCTION Today’s Speakers President and Chief Operating Officer Chairperson and Chief Executive Officer Michael Benkowitz Dr. Martine Rothblatt Associate Professor of Medicine, University of Rochester Medicine Dr. Daniel Lachant, DO, MSCI, ATSF Senior Director, Product Development and Lead for the Global ADVANCE OUTCOMES Program Dr. Derek Solum Executive Vice President, Product Development and Xenotransplantation Dr. Leigh Peterson |
| 4 CHAIRPERSON AND CHIEF EXECUTIVE OFFICER Dr. Martine Rothblatt |
| 5 ADVANCE OUTCOMES RESULTS ADVANCE OUTCOMES Headline Conclusions The study also met several important secondary endpoints, including change in NT-proBNP1, 6MWD2, and clinical improvement 1 Treatment with ralinepag was well-tolerated, and the safety profile was consistent with known prostacyclin-related adverse events. No new safety signals were observed. Ralinepag reduced the risk of a clinical worsening event versus placebo by 55% (HR: 0.45, [95% CI: 0.33- 0.62]; p<0.0001) 2 3 1. NT-proBNP=N-terminal pro-B-type natriuretic peptide 2. 6MWD=six-minute walk distance The use of ralinepag for PAH is an investigational use and has not been approved by the FDA |
| 6 SENIOR DIRECTOR, PRODUCT DEVELOPMENT AND LEAD FOR THE GLOBAL ADVANCE OUTCOMES PROGRAM Dr. Derek Solum |
| 7 ADVANCE OUTCOMES DESIGN ADVANCE OUTCOMES Study Design1 Time from randomization to the first adjudicated protocol-defined clinical worsening event 1. https://clinicaltrials.gov/study/NCT03626688 2. WHO = World Health Organization. 3. NYHA = New York Heart Association 4. Defined by the absence of clinical worsening and fulfillment of at least 2 of the 3 of the following: increase in 6MWD ≥10% or ≥30 m, improvement to or maintenance of WHO FC I or II, and decrease in NT-proBNP by at least 30%. 5. Subjects who attain all 3 of the following: NT-proBNP <300 pg/mL, 6MWD >440 m, WHO/NYHA FC I or II 6. REVEAL = Registry to Evaluate Early and Long-term PAH Disease Management 7. HRQoL = Health-related quality of life 8. HRR = Heart rate recovery 9. 6MWT = 6-Minute Walk Test PRIMARY ENDPOINT Change from Baseline to Week 28 in: • NT-proBNP • 6MWD • WHO2/NYHA3 Functional Class Clinical improvement4 Time to first all-cause nonelective hospitalization Time to all-cause mortality Shift and proportion of subjects5 REVEAL6 risk score HRQoL7 measures HRR8 following completion of 6MWT9 Safety and tolerability SECONDARY ENDPOINTS STUDY VISIT SCHEDULE All participants receiving PAH standard of care or PAH-specific background therapy were randomized 1:1. Treatment Period lasted until the 180th adjudicated clinical worsening event. |
| 8 ADVANCE OUTCOMES DESIGN ADVANCE OUTCOMES Study Design1 A protocol-defined clinical worsening event is defined as 1 of the following: • Death (all causes) • Nonelective hospital admission lasting at least 24 hours and/or right heart failure inclusive of lung transplant, heart/lung transplant, or atrial septostomy • Initiation of parenteral (intravenous [IV] or subcutaneous [SC] infusion) or inhaled therapy with a prostacyclin pathway agent • Disease progression, defined as: o A decrease in 6-Minute Walk Distance (6MWD) of at least 15% from Baseline: § A worsening from Baseline of at least 1 WHO Functional Class (FC) § Initiation of additional PAH-specific therapy • Unsatisfactory long-term clinical response (all criteria required) o Has received study drug for at least 28 weeks o A decrease from Baseline in 6MWD at or after Week 28 o Sustained WHO FC III or IV symptoms for at least 28 consecutive weeks 1. https://clinicaltrials.gov/study/NCT03626688 CLINICAL WORSENING DEFINITION |
| 9 ADVANCE OUTCOMES BASELINE Baseline Demographics of Enrolled Subjects Ralinepag N=350 Placebo N=337 Overall N=687 Age at Study Entry (years), median (range) 54.0 (18, 83) 52.0 (19, 84) 53.0 (18, 84) Female (%)/Male (%) 256 (73.1)/94 (26.9) 264 (78.3)/73 (21.7) 520 (75.7)/167 (24.3) Time Since Diagnosis (years), mean (SD) 4.3 (5.6) 4.8 (6.4) 4.5 (6.0) Ethnicity, n (%) Hispanic or Latino 95 (27.1) 100 (29.7) 195 (28.4) Not Hispanic or Latino 235 (67.1) 222 (65.9) 457 (66.5) Race, n (%) White 283 (80.9) 268 (79.5) 551 (80.2) Black 10 (2.9) 12 (3.6) 22 (3.2) Native Hawaiian/Pacific Islander 2 (0.6) 1 (0.3) 3 (0.4) Asian 21 (6.0) 38 (11.3) 59 (8.6) Multiple 2 (0.6) 4 (1.2) 6 (0.9) Other 18 (5.1) 11 (3.3) 29 (4.2) Not Reported 13 (3.7) 3 (0.9) 16 (2.3) |
| 10 ADVANCE OUTCOMES BASELINE Baseline Demographics Cont’d Ralinepag N=350 Placebo N=337 Overall N=687 Weight (kg), mean (SD) 73.2 (16.3) 73.8 (17.9) 73.5 (17.1) Background Therapy One or No Background Therapy, n (%) 68 (19.4) 71 (21.1) 139 (20.2) Dual Background Therapy, n (%) 282 (80.6) 266 (78.9) 548 (79.8) Baseline 6MWD (m), mean (SD) 441.3 (106.9) 436.5 (102.7) 438.9 (104.8) 6MWD <400m, n (%) 118 (33.7) 118 (35.0) 236 (34.4) ≥400m, n (%) 232 (66.3) 219 (65.0) 461 (67.1) WHO Functional Class, n (%) II 261 (74.6) 223 (66.2) 484 (70.5) III 89 (29.4) 113 (33.5) 202 (29.4) IV 0 1 (0.3) 1 (0.1) |
| 11 ADVANCE OUTCOMES RESULTS Primary Endpoint Time to Adjudication Clinical Worsening (Weeks); Kaplan-Meier Estimates 1. P value is calculated with log rank test stratified by background PAH therapy and baseline 6MWD category. 2. Hazard ratio, 95% CI, and P value are calculated with proportional hazard model with treatment and the randomization stratification factors in the model. |
| 12 ADVANCE OUTCOMES RESULTS Primary Endpoint Adjudicated Clinical Worsening Events 1. Hazard ratio, 95% CI, and P value are calculated with proportional hazard model with treatment and the randomization stratification factors in the model. Ralinepag Placebo N=350 % N=337 % Clinical worsening event category as the first event n(%) All events 64 18.3% 121 35.9% Death (all causes) 11 3.1% 10 3.0% Hospitalization due to PAH 19 5.4% 20 5.9% Disease Progression 10 2.9% 36 10.7% Initiation of inhaled or infused prostacyclin 10 2.9% 22 6.5% Unsatisfactory long-term clinical response 14 4.0% 33 9.8% Hazard Ratio (95% Cl) (Ralinepag - Placebo)1 0.45 (0.33, 0.62) P<0.0001 |
| 13 ADVANCE OUTCOMES RESULTS Primary Endpoint Time to Disease Progression; Kaplan-Meier Estimates |
| 14 ADVANCE OUTCOMES RESULTS Subgroup Analyses Time to First Clinical Worsening Event Subgroup Ralinepag Placebo Hazard Ratio (95% CI) # of Events / # of Patients 0.45( 0.33, 0.62) 0.52( 0.35, 0.76) 0.41( 0.25, 0.67) 0.32( 0.19, 0.56) 0.53( 0.37, 0.77) 0.45( 0.32, 0.64) 0.46( 0.25, 0.84) 0.60( 0.41, 0.87) 0.28( 0.16, 0.48) 0.41( 0.21, 0.80) 0.47( 0.33, 0.66) 0.0 0.5 1.0 1.5 2.0 Ralinepag <- Favors -> Placebo 121/337 67/112 54/225 40/94 81/243 91/265 30/72 85/262 36/75 22/73 99/264 64/350 41/114 23/236 19/100 45/250 47/283 17/67 43/260 21/90 14/94 50/256 Overall Baseline 6MWD <400 m >=400 m Etiology CTD Associated Other Etiology Background PAH Therapy Two One or Zero Age at Baseline <65 yrs >=65 yrs Sex Male Female |
| 15 ADVANCE OUTCOMES RESULTS Subgroup Analyses Time to First Clinical Worsening Event Subgroup Ralinepag Placebo Hazard Ratio (95% CI) # of Events / # of Patients 0.46( 0.30, 0.72) 0.50( 0.32, 0.77) ND 0.26( 0.03, 2.07) 0.43( 0.20, 0.90) 0.45( 0.32, 0.64) 0.41( 0.25, 0.68) 0.42( 0.22, 0.79) 0.47( 0.24, 0.91) 0.77( 0.35, 1.68) 0.24( 0.13, 0.44) 0.64( 0.38, 1.05) 0.47( 0.24, 0.91) 0.44( 0.31, 0.62) 0.0 0.5 1.0 1.5 2.0 Ralinepag <- Favors -> Placebo 56/223 65/114 5/6 9/17 16/49 91/265 22/66 99/271 26/96 15/51 39/106 41/84 26/96 95/241 32/261 32/89 2/8 1/14 14/45 47/283 53/302 11/48 14/81 11/46 14/139 25/84 14/81 50/269 Baseline WHO FC WHO FC II WHO FC III or IV PAH Therapy at Baseline None ERA PDE5-I/sGC ERA + PDE5-I/sGC Maximum Dose Achieved <600 mcg >=600 mcg Geographic Region North America Asia-Pacific Europe South and Latin America Location North America Rest of World |
| 16 ADVANCE OUTCOMES RESULTS Subgroup Analyses Time to First Clinical Worsening Event Subgroup Ralinepag Placebo Hazard Ratio (95% CI) # of Events / # of Patients 0.40( 0.23, 0.67) 0.48( 0.33, 0.70) 0.45( 0.26, 0.76) 0.46( 0.32, 0.68) 0.42( 0.22, 0.81) 0.37( 0.26, 0.53) 0.45( 0.31, 0.67) 0.43( 0.26, 0.73) 0.60( 0.35, 1.03) 0.42( 0.25, 0.71) 0.45( 0.23, 0.89) 0.33( 0.12, 0.92) 0.0 0.5 1.0 1.5 2.0 Ralinepag <- Favors -> Placebo 45/168 76/169 40/169 80/167 39/177 81/158 62/157 59/179 32/42 48/93 26/97 14/103 20/167 44/182 21/173 43/176 12/163 51/183 45/186 19/164 24/42 22/79 12/115 5/110 Baseline mean PAP <median (44 mmHg) >=median (44 mmHg) Baseline PVR <median (577 dyn.sec/cm5) >=median (577 dyn.sec/cm5) Baseline plasma NT-proBNP <median (213 pg/mL) >=median (213 pg/mL) Time since PAH diagnosis <median (2.285 years) >=median (2.285 years) Baseline Risk Category* 0 1 2 3 |
| 17 ADVANCE OUTCOMES RESULTS Summary of Most Commonly Reported Adverse Events by Preferred Term Ralinepag N=350 Placebo N=337 Preferred Term n (%) n (%) Any Event 346 (98.9%) 320 (95.0%) Headache 284 (81.1%) 140 (41.5%) Diarrhea 204 (58.3%) 95 (28.2%) Nausea 158 (45.1%) 86 (25.5%) Myalgia 126 (36.0%) 36 (10.7%) Pain in jaw 125 (35.7%) 30 (8.9%) Note: Table reflects top 5 most reported adverse events. |
| 18 ADVANCE OUTCOMES RESULTS ADVANCE OUTCOMES Headline Conclusions The study also met several important secondary endpoints, including change in NT-proBNP1, 6MWD2, and clinical improvement 1 Treatment with ralinepag was well-tolerated, and the safety profile was consistent with known prostacyclin-related adverse events. No new safety signals were observed. Ralinepag reduced the risk of a clinical worsening event versus placebo by 55% (HR: 0.45, [95% CI: 0.33- 0.62]; p<0.0001) 2 3 1. NT-proBNP=N-terminal pro-B-type natriuretic peptide 2. 6MWD=six-minute walk distance The use of ralinepag for PAH is an investigational use and has not been approved by the FDA |
| 19 ASSOCIATE PROFESSOR OF MEDICINE, UNIVERSITY OF ROCHESTER Dr. Daniel Lachant, DO, MSCI, ATSF |
| 20 CHAIRPERSON & CHIEF EXECUTIVE OFFICER Dr. Martine Rothblatt |
| 21 Q&A Dr. Martine Rothblatt Chairperson and Chief Executive Officer Michael Benkowitz President and Chief Operating Officer Dr. Leigh Peterson EVP, Product Development and Xenotransplantation Dr. Derek Solum Senior Director, Product Development and Lead for the Global ADVANCE OUTCOMES Program Dr. Daniel Lachant, DO, MSCI, ATSF Associate Professor of Medicine, University of Rochester Harry Silvers Investor Relations We are incredibly thankful to the participants, investigators, and research teams whose work contributed to the development of ralinepag |
FAQ
What did United Therapeutics (UTHR) report about the ADVANCE OUTCOMES study?
How effective was ralinepag in treating pulmonary arterial hypertension in this trial?
What makes ralinepag potentially different from existing PAH treatments?
When does United Therapeutics (UTHR) plan to seek FDA approval for ralinepag?
What safety profile did ralinepag show in the ADVANCE OUTCOMES phase 3 study?
Is United Therapeutics hosting an event to discuss the ralinepag trial results?
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