Drug Trials Snapshots: OHTUVAYRE
HOW TO USE THIS SNAPSHOT
The information provided in Snapshots highlights who participated in the key clinical trials that supported the original FDA approval of this drug and whether there were differences among sex, race, age, and ethnic groups. The “MORE INFO” bar shows more detailed, technical content for each section. The Snapshot is intended as one tool for consumers to use when discussing the risks and benefits of the drugs.
LIMITATIONS OF THIS SNAPSHOT
Do not rely on Snapshots to make decisions regarding medical care. Always speak to your healthcare provider about the benefits and risks of a drug.
Some of the information in this Snapshot is for presentation purposes and does not represent the approved conditions of use of this drug. Refer to the OHTUVAYRE Prescribing Information for all the approved conditions of use of this drug (e.g., indication(s), population(s), dosing regimen(s), safety information).
Snapshots are limited to the information available at the time of the original approval of the drug and do not provide information on who participated in clinical trials that supported later approvals for additional uses of the drug (if applicable).
OHTUVAYRE (ensifentrine)
OH-too-vare
Verona Pharma
Original Approval Date: June 26, 2024
DRUG TRIALS SNAPSHOT SUMMARY
What is the drug for?
OHTUVAYRE is a phosphodiesterase 3 and phosphodiesterase 4 inhibitor that is indicated for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adult patients. COPD is a chronic respiratory condition and is one of the leading causes of death in the United States.
How is this drug used?
OHTUVAYRE is administered by oral inhalation taken twice a day using a standard jet nebulizer with a mouthpiece.
Who participated in the clinical trials?
The FDA approved OHTUVAYRE based on evidence from two placebo-controlled clinical trials that enrolled 1,553 adult patients with moderate to severe COPD (ENHANCE-1 and ENHANCE-2). The trials were conducted in 17 countries, including Belgium, Bulgaria, Canada, Czech Republic, Denmark, Estonia, Germany, Greece, Hungary, Poland, Romania, Russia, Slovakia, South Korea, Spain, the United Kingdom, and the United States. ENHANCE-1 enrolled patients in 120 centers, and ENHANCE-2 enrolled patients in 100 centers.
How were the trials designed?
OHTUVAYRE was evaluated in two placebo-controlled clinical trials of 1,553 adult patients with moderate to severe COPD. Both trials randomized patients in a 5:3 ratio to receive OHTUVAYRE or placebo. The primary endpoint for both trials evaluated pulmonary function as measured by the change from baseline in the forced expiratory volume in 1 second (FEV1) area under the concentration-time curve over 12 hours.
How were the trials designed?
The efficacy and safety of OHTUVAYRE were evaluated in two phase 3 randomized, double-blind, placebo-controlled parallel-group trials in adults with moderate to severe COPD treated for at least 24 weeks. The trials randomized patients 5:3 to receive OHTUVAYRE 3 mg or placebo (normal saline) delivered via a standard jet nebulizer twice daily. The primary endpoint was the change from baseline in FEV1 area under the concentration-time curve from 0 to 12 hours at Week 12. Secondary endpoints included the morning trough FEV1, the lung function value immediately before the next dose is required.
DEMOGRAPHICS SNAPSHOT
Figure 1. Baseline Demographics by Sex Efficacy Population
Figure 1 summarizes how many male and female patients were enrolled in the combined clinical trials used to evaluate the efficacy of OHTUVAYRE.
Source: Adapted from FDA Review
Figure 2. Baseline Demographics by Race Efficacy Population
Figure 2 summarizes how many patients by race were enrolled in the combined clinical trials used to evaluate the efficacy of OHTUVAYRE.
Source: Adapted from FDA Review
Figure 3. Baseline Demographics by Age Efficacy Population
Figure 3 summarizes how many patients by age were enrolled in the combined clinical trials used to evaluate the efficacy of OHTUVAYRE.
Source: Adapted from FDA Review
Figure 4. Baseline Demographics by Ethnicity Efficacy Population
Figure 4 summarizes how many patients by ethnicity were enrolled in the combined clinical trials used to evaluate the efficacy of OHTUVAYRE.
Source: Adapted from FDA Review
Who participated in the trials?
Table 1. Baseline Demographics, Efficacy Population
| Characteristic | OHTUVAYRE N=978 n (%) | Placebo N=575 n (%) |
|---|---|---|
| Sex | ||
| Female | 458 (46.8) | 270 (47.0) |
| Male | 520 (53.2) | 305 (53.0) |
| Age group, years | ||
| <65 | 444 (45.4) | 257 (44.7) |
| ≥65 | 534 (54.6) | 318 (55.3) |
| Race | ||
| Asian | 14 (1.4) | 12 (2.1) |
| Black or African American | 40 (4.1) | 20 (3.5) |
| Not reported | 14 (1.4) | 12 (2.1) |
| Other | 1 (0.1) | 4 (0.7) |
| White | 909 (92.9) | 527 (91.7) |
| Ethnicity | ||
| Hispanic or Latino | 41 (4.2) | 20 (3.5) |
| Not Hispanic or Latino | 937 (95.8) | 555 (96.5) |
| Is in United States | ||
| United States | 368 (37.6) | 232 (40.3) |
| Non-United States | 610 (62.4) | 343 (59.7) |
Source: Adapted from FDA Review
What are the benefits of this drug?
OHTUVAYRE improved pulmonary function in adults with moderate to severe COPD compared to placebo. This was measured by the primary endpoint of the change from baseline in the FEV1 area under the concentration-time curve over 12 hours after 12 weeks of treatment.
What are the benefits of this drug (results of trials used to assess efficacy)?
The two placebo-controlled trials of OHTUVAYRE demonstrated statistically significant improvements in the pulmonary function of adults with moderate to severe COPD compared to placebo. This was measured by the primary endpoint of the change from baseline in the FEV1 area under the concentration-time curve over 12 hours after 12 weeks of treatment. The efficacy was also supported by the results of the secondary spirometry endpoints including the peak FEV1, the FEV1 area under the concentration-time curve from 0 to 4 hours, and morning trough FEV1. Table 2 reviews the efficacy results of the two placebo-controlled trials of OHTUVAYRE.
Table 2. LS Mean Change From Baseline in FEV1 Area Under the Concentration-Time Curve From 0 to 12 Hours (mL) at Week 12, Efficacy Population
| Parameter | ENHANCE-1 | ENHANCE-2 | ||
|---|---|---|---|---|
| OHTUVAYRE N=479 | Placebo N=284 | OHTUVAYRE N=499 | Placebo N=291 | |
| n | 477 | 282 | 498 | 291 |
| LS mean (95% CI) | 61 (25, 97) | -26 (-64, 13) | 48 (30, 66) | -46 (-70, -22) |
| LS mean difference from placebo (95% CI) | 87 (55, 118) | 94 (65, 124) | ||
| p-value | <0.0001 | <0.0001 | ||
Source: Adapted from OHTUVAYRE Prescribing Information
Abbreviations: CI, confidence interval; FEV1, forced expiratory volume in 1 second; LS, least squares; N, number of all enrolled patients; n, number of patients who received at least one dose of study drug and had non-missing baseline FEV1 value
Were there any differences in how well the drug worked in clinical trials among sex, race, and age?
- Sex: OHTUVAYRE worked similarly in males and females.
- Race: Most of the patients enrolled in the trials were White. Differences in how well OHTUVAYRE worked among races could not be determined because of the small number of patients of other races.
- Age: OHTUVAYRE worked similarly in patients younger and older than 65 years of age.
Were there any differences in how well the drug worked in clinical trials among sex, race, and age groups?
Subgroup analyses of the primary endpoint based on age, sex at birth, and race were performed. In general, there were no significant differences in the efficacy of OHTUVAYRE based on the demographic subgroups. The subgroup efficacy analysis data is included in Table 3.
Table 3. Efficacy Results by Subgroup, Change From Baseline in FEV1 Area Under the Concentration-Time Curve Over 12 Hours, Efficacy Population
| Subgroup | ENHANCE-1 | ENHANCE-2 | ||
|---|---|---|---|---|
| n[O], n[P] | LS Mean Difference From Placebo (95% CI) | n[O], n[P] | LS Mean Difference From Placebo (95% CI) | |
| Age, years | ||||
| <65 | 219, 132 | 70 mL (15, 125) | 224, 124 | 87 mL (39, 135) |
| ≥65 | 258, 150 | 102 mL (67, 138) | 274, 167 | 100 mL (63, 136) |
| Sex | ||||
| Female | 203, 116 | 91 mL (51, 131) | 254, 153 | 75 mL (39, 112) |
| Male | 274, 166 | 85 mL (39, 131) | 244, 138 | 114 mL (68, 161) |
| Race | ||||
| White | 435, 249 | 88 mL (55, 122) | 471, 276 | 92 mL (62, 122) |
| Other1 | 42, 33 | 69 mL (-16, 153) | 27, 15 | 154 mL (-6, 314) |
Source: Adapted from FDA Review
1Other includes Asian, Black or African American, other, and subjects whose race was not reported.
Abbreviations: CI, confidence interval; FEV1, forced expiratory volume in 1 second; LS, least squares; n[O], number of subjects who received at least one dose of study drug and had non-missing baseline FEV1 value in OHTUVAYRE arm; n[P], number of subjects who received at least one dose of study drug and had non-missing baseline FEV1 value in placebo arm.
What are the possible side effects?
The most common side effects of OHTUVAYRE included back pain, high blood pressure, bladder infection, and diarrhea. In addition, OHTUVAYRE may cause more rare, serious side effects including sudden breathing problems immediately after inhaling the medication and mental health problems including suicidal thoughts and behaviors. Patients should call their healthcare provider if experiencing these rare side effects.
What are the possible side effects (results of trials used to assess safety)?
The safety of OHTUVAYRE was based on the combined safety population from the two placebo-controlled trials (ENHANCE-1 and ENHANCE-2). The side effects that occurred at a rate of greater than or equal to 1% included back pain, hypertension, urinary tract infection, and diarrhea and are reviewed in Table 4. More serious potential side effects included paradoxical bronchospasm (e.g., sudden breathing problems immediately after inhaling the medication) and mental health problems including suicidal thoughts and behaviors.
Table 4. Safety Results, Safety Population
| Adverse Reaction | OHTUVAYRE N=975 n (%) | Placebo N=574 n (%) |
|---|---|---|
| Back pain | 18 (1.8) | 6 (1.0) |
| Hypertension | 17 (1.7) | 5 (0.9) |
| Urinary tract infection | 13 (1.3) | 6 (1.0) |
| Diarrhea | 10 (1.0) | 4 (0.7) |
Source: OHTUVAYRE Prescribing Information
Were there any differences in side effects among sex, race, and age?
- Sex: The occurrence of side effects was similar in males and females.
- Race: Most of the patients enrolled in the trials were White. Differences in the occurrence of side effects among races could not be determined because of the small numbers of patients of other races.
- Age: The occurrence of side effects was similar in patients younger and older than 65 years of age.
Were there any differences in side effects of the clinical trials among sex, race, and age groups?
A safety analysis by key demographic subgroups including age, sex at birth, race, ethnicity, and region (United States versus outside the United States) was performed. There were no significant differences noted between subgroups. The side effects by demographic subgroups are reviewed in Table 5.
Table 5. Side Effects by Subgroup, Safety Population
| Subgroup | OHTUVAYRE N=975 n/Ns (%) | Placebo N=574 n/Ns (%) |
|---|---|---|
| Sex | ||
| Female | 183/457 (40.0) | 105/269 (39.0) |
| Male | 176/518 (34.0) | 101/305 (33.1) |
| Age group, years | ||
| <65 | 172/443 (38.8) | 91/257 (35.4) |
| ≥65 | 187/532 (35.2) | 115/317 (36.3) |
| Race | ||
| Asian | 2/14 (14.3) | 5/12 (41.7) |
| Black or African American | 13/40 (32.5) | 4/20 (20.0) |
| Not reported | 9/14 (64.3) | 8/12 (66.7) |
| Other | 0/1 (0) | 3/4 (75.0) |
| White | 335/906 (37.0) | 186/526 (35.4) |
| Ethnicity | ||
| Hispanic or Latino | 12/41 (29.3) | 9/20 (45.0) |
| Not Hispanic or Latino | 347/934 (37.2) | 197/554 (35.6) |
| Is in United States | ||
| United States | 157/367 (42.8) | 90/232 (38.8) |
| Non-United States | 202/608 (33.2) | 116/342 (33.9) |
Source: Adapted from FDA Review
Abbreviations: N, number of patients in treatment arm; n, number of patients with adverse event; Ns, total number of patients for each specific subgroup and were assigned to that specific arm.
GLOSSARY
CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.
COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.
EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.
PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.
SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.