Adempas (riociguat) | Efficacy + Results

IF YOUR PATIENTS ARE NOT AT GOAL, CONSIDER ADEMPAS

Adempas demonstrated efficacy for CTEPH adult patients in both WHO Functional Class II and III by 3 parameters¹

Improvement in 6MWD

Improvement in WHO FC

Improvement in PVR and NT-proBNP

6MWD=6-minute walking distance; CTEPH=chronic thromboembolic pulmonary hypertension; NT-proBNP=N-terminal pro-brain natriuretic peptide; PVR=pulmonary vascular resistance; WHO FC=World Health Organization Functional Class.

CHEST STUDY DESIGN^1,2

Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase–Stimulator Trial 1 (CHEST-1) was a randomized, double-blind, multinational, multicenter, placebo-controlled, 16-week phase 3 study.

Baseline Characteristics

Mean age: 59 years (range: 18-80)
Mean 6MWD was 347 m
Concomitant medications: stable dosages of oral anticoagulants, diuretics, digitalis, calcium channel blockers, and oxygen were allowed, but not nitric oxide donors, endothelin receptor antagonists, prostacyclin analogues, specific PDE-5 inhibitors (such as sildenafil, tadalafil, or vardenafil), and nonspecific PDE inhibitors (for example, dipyridamole or theophylline)

The majority of patients were WHO FC II (31%) or III (64%) at baseline. Patients with systolic blood pressure <95 mm Hg were excluded.

CHEST-1 was a pivotal trial for inoperable or persistent/recurrent CTEPH (WHO Group 4) patients.
PDE-5=phosphodiesterase type 5; PH=pulmonary hypertension; PTE=pulmonary thromboendarterectomy.

Exercise Capacity (6MWD)

ADEMPAS SIGNIFICANTLY IMPROVED 6MWD AT WEEK 16¹

Results in CTEPH: 6MWD Over 16 Weeks

Patient Subgroups

CTEPH^* PATIENTS WALKED FARTHER WITH ADEMPAS AT WEEK 16^1,3

Prespecified Subgroup: Mean Change From Baseline

WHO Functional Class Improvement

50% MORE PATIENTS IN THE ADEMPAS^† GROUP IMPROVED IN WHO FC VS PLACEBO AT WEEK 16¹

Change in WHO Functional Class in the 16-Week Trial

Hemodynamics (PVR and NT-proBNP)

ADEMPAS IMPROVED PVR AND NT-proBNP AT WEEK 16^1,2‡

Change in Hemodynamic Parameters at Week 16

Long-Term Data

MORE THAN 90% OF ADEMPAS PATIENTS SURVIVED AT 2 YEARS^1§

Probability of Survival Data for CTEPH Patients

^§Data from CHEST-2 open-label extension study.

An open-label extension study (CHEST-2) included 237 patients who had completed CHEST-1.

At the cut-off date in the CHEST-2 study, the mean treatment duration for the total population was 1077 days (±433).

Without a control group, these data must be interpreted cautiously.

Most Common Adverse Events

ADVERSE EVENTS THAT OCCURRED MORE FREQUENTLY (≥3%) ON ADEMPAS THAN PLACEBO (POOLED FROM CHEST-1 AND PATENT-1)¹

Other events that were seen more frequently in Adempas compared to placebo and potentially related to treatment were:

Palpitations
Nasal congestion
Epistaxis
Dysphagia
Abdominal distention
Peripheral edema

IF YOUR PATIENTS ARE NOT AT GOAL, CONSIDER ADEMPAS

Adempas demonstrated efficacy for CTEPH adult patients in both WHO Functional Class II and III by 3 parameters¹

Improvement in 6MWD

Improvement in WHO FC

Improvement in PVR and NT-proBNP

CHEST STUDY DESIGN^1,2

Baseline Characteristics

Mean age: 59 years (range: 18-80)
Mean 6MWD was 347 m
Concomitant medications: stable dosages of oral anticoagulants, diuretics, digitalis, calcium channel blockers, and oxygen were allowed, but not nitric oxide donors, endothelin receptor antagonists, prostacyclin analogues, specific PDE-5 inhibitors (such as sildenafil, tadalafil, or vardenafil), and nonspecific PDE inhibitors (for example, dipyridamole or theophylline)

PATIENT POPULATION

72%

inoperable by PTE

(PVR >300 dyn·sec·cm^-5and mean pulmonary arterial pressure >25 mm Hg measured at least 90 days after the start of full anticoagulation)

28%

recurrent or persisting PH

(PVR >300 dyn·sec·cm^-5measured at least 180 days following PTE)

The majority of patients were WHO FC II (31%) or III (64%) at baseline. Patients with systolic blood pressure <95 mm Hg were excluded.

EXERCISE CAPACITY

Exercise Capacity (6MWD)

ADEMPAS SIGNIFICANTLY IMPROVED 6MWD AT WEEK 16¹

Results in CTEPH: 6MWD Over 16 Weeks

improvement (mean) in 6-minute walk distance (6MWD) over placebo at Week 16 (95% confidence interval (CI): 25 m-67 m; p<0.0001) for adults with CTEPH (WHO Group 4).

PATIENT SUBGROUPS

Patient Subgroups

CTEPH^* PATIENTS WALKED FARTHER WITH ADEMPAS AT WEEK 16^1,3

Prespecified Subgroup: Mean Change From Baseline

WHO FC IMPROVEMENT

WHO Functional Class Improvement

50% MORE PATIENTS IN THE ADEMPAS^† GROUP IMPROVED IN WHO FC VS PLACEBO AT WEEK 16¹

Change in WHO Functional Class in the 16-Week Trial

as many patients improved WHO FC vs placebo

HEMODYNAMICS

Hemodynamics (PVR and NT-proBNP)

ADEMPAS IMPROVED PVR AND NT-proBNP AT WEEK 16^1,2‡

Change in Hemodynamic Parameters at Week 16

LONG TERM DATA

Long-Term Data

MORE THAN 90% OF ADEMPAS PATIENTS SURVIVED AT 2 YEARS^1§

Probability of Survival Data for CTEPH Patients

^§Data from CHEST-2 open-label extension study.

An open-label extension study (CHEST-2) included 237 patients who had completed CHEST-1.

At the cut-off date in the CHEST-2 study, the mean treatment duration for the total population was 1077 days (±433).

Without a control group, these data must be interpreted cautiously.

ADVERSE EVENTS

Most Common Adverse Events

ADVERSE EVENTS THAT OCCURRED MORE FREQUENTLY (≥3%) ON ADEMPAS THAN PLACEBO (POOLED FROM CHEST-1 AND PATENT-1)¹

Other events that were seen more frequently in Adempas compared to placebo and potentially related to treatment were:

Palpitations
Nasal congestion
Epistaxis

Dysphagia
Abdominal distention
Peripheral edema

MORE IMPORTANT SAFETY INFORMATION LESS IMPORTANT SAFETY INFORMATION

Important Safety Information and Indications

WARNING: EMBRYO-FETAL TOXICITY

Do not administer Adempas (riociguat) tablets to a pregnant female because it may cause fetal harm.

Females of reproductive potential: Exclude pregnancy before the start of treatment, monthly during treatment, and one month after stopping treatment. To prevent pregnancy, females of reproductive potential must use effective forms of contraception during treatment and for one month after stopping treatment.

For all female patients, Adempas is available only through a restricted program called the Adempas Risk Evaluation and Mitigation Strategy (REMS) Program.

Contraindications

Adempas is contraindicated in:

Pregnancy. Based on data from animal reproduction studies, Adempas may cause fetal harm when administered to a pregnant woman and is contraindicated in females who are pregnant. Adempas was consistently shown to have teratogenic effects when administered to animals. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.
Co-administration with nitrates or nitric oxide donors (such as amyl nitrite) in any form.
Concomitant administration with specific phosphodiesterase (PDE)-5 inhibitors (such as sildenafil, tadalafil, or vardenafil) or nonspecific PDE inhibitors (such as dipyridamole or theophylline) is contraindicated. Do not administer within 24 hours of sildenafil. Do not administer 24 hours before or within 48 hours after tadalafil.
Patients with concomitant use of other soluble guanylate cyclase (sGC) stimulators.
Patients with Pulmonary Hypertension associated with Idiopathic Interstitial Pneumonias (PH-IIP).

Warnings and Precautions

Embryo-Fetal Toxicity. Based on data from animal reproduction studies, Adempas may cause embryo-fetal toxicity when administered to a pregnant female and is contraindicated in females who are pregnant. Advise females of reproductive potential of the potential risk to a fetus. Obtain a pregnancy test before the start of treatment, monthly during treatment, and for one month after stopping treatment. Advise females of reproductive potential to use effective contraception during treatment with Adempas and for at least one month after the last dose.

For females, Adempas is only available through a restricted program under the Adempas REMS Program.

Adempas REMS Program. Females can only receive Adempas through the Adempas REMS Program, a restricted distribution program.

Important requirements of the Adempas REMS Program include the following:

Prescribers must be certified with the program by enrolling and completing training.
All females, regardless of reproductive potential, must enroll in the Adempas REMS Program prior to initiating Adempas. Male patients are not enrolled in the Adempas REMS Program.
Female patients of reproductive potential must comply with the pregnancy testing and contraception requirements.
Pharmacies must be certified with the program and must only dispense to patients who are authorized to receive Adempas.

Further information, including a list of certified pharmacies, is available at www.AdempasREMS.com or 1-855-4ADEMPAS.

Hypotension. Adempas reduces blood pressure. Consider the potential for symptomatic hypotension or ischemia in patients with hypovolemia, severe left ventricular outflow obstruction, resting hypotension, autonomic dysfunction, or concomitant treatment with antihypertensives or strong CYP and P-gp/BCRP inhibitors. Consider a dose reduction if patient develops signs or symptoms of hypotension.

Bleeding. In the placebo-controlled clinical trials, serious bleeding occurred in 2.4% of patients taking Adempas compared to 0% of placebo patients. Serious hemoptysis occurred in 5 (1%) patients taking Adempas compared to 0 placebo patients, including one event with fatal outcome. Serious hemorrhagic events also included 2 patients with vaginal hemorrhage, 2 with catheter-site hemorrhage, and 1 each with subdural hematoma, hematemesis, and intra-abdominal hemorrhage.

Pulmonary Veno-Occlusive Disease. Pulmonary vasodilators may significantly worsen the cardiovascular status of patients with pulmonary veno-occlusive disease (PVOD). Therefore, administration of Adempas to such patients is not recommended. Should signs of pulmonary edema occur, the possibility of associated PVOD should be considered and if confirmed, discontinue treatment with Adempas.

Most Common Adverse Reactions

The most common adverse reactions occurring more frequently (≥3%) on Adempas than placebo were headache (27% vs 18%), dyspepsia/gastritis (21% vs 8%), dizziness (20% vs 13%), nausea (14% vs 11%), diarrhea (12% vs 8%), hypotension (10% vs 4%), vomiting (10% vs 7%), anemia (7% vs 2%), gastroesophageal reflux disease (5% vs 2%), and constipation (5% vs 1%).

Other events that were seen more frequently in Adempas compared to placebo and potentially related to treatment were palpitations, nasal congestion, epistaxis, dysphagia, abdominal distension, and peripheral edema.

Indications

Adempas (riociguat) is indicated for the treatment of adults with persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) (WHO Group 4) after surgical treatment or inoperable CTEPH to improve exercise capacity and WHO functional class.
Adempas is indicated for the treatment of adults with pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise capacity, improve WHO functional class and to delay clinical worsening.*

Efficacy was shown in patients on Adempas monotherapy or in combination with endothelin receptor antagonists or prostanoids. Studies establishing effectiveness included predominantly patients with WHO functional class II–III and etiologies of idiopathic or heritable PAH (61%) or PAH associated with connective tissue diseases (25%).

^*Time to clinical worsening was a combined endpoint defined as death (all-cause mortality), heart/lung transplantation, atrial septostomy, hospitalization due to persistent worsening of pulmonary hypertension, start of new PAH-specific treatment, persistent decrease in 6MWD, and persistent worsening of WHO functional class.

For important risk and use information, please see the full Prescribing Information, including Boxed Warning.

References:

Adempas Prescribing Information. Whippany, NJ. Bayer Pharmaceuticals Inc., 2021.
Ghofrani HA, D’Armini AM, Grimminger F, et al. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension. N Engl J Med. 2013;369(4):319-329.
Clinical Study Report A62508. Data on File. Bayer HealthCare, Inc; Whippany, NJ.

CTEPH EFFICACY + SAFETY RESULTS

Adempas is the first and only FDA-approved treatment for adults with inoperable/recurrent CTEPH (WHO Group 4) after surgery.¹

IF YOUR PATIENTS ARE NOT AT GOAL, CONSIDER ADEMPAS

WARNING: EMBRYO-FETAL TOXICITY

CTEPH EFFICACY + SAFETY RESULTS

Adempas is the first and only FDA-approved treatment for adults with inoperable/recurrent CTEPH (WHO Group 4) after surgery.1

IF YOUR PATIENTS ARE NOT AT GOAL, CONSIDER ADEMPAS

WARNING: EMBRYO-FETAL TOXICITY

Adempas is the first and only FDA-approved treatment for adults with inoperable/recurrent CTEPH (WHO Group 4) after surgery.¹