| Drug Name |
OHTUVAYRE™ (ensifentrine) |
| Active Ingredient |
ensifentrine |
| Date of Approval |
June 26, 2024 |
| Manufacturer |
Verona Pharma plc |
| Approval Pathways and Indications |
Approval Pathway: NDA
Indication: OHTUVAYRE™ is indicated for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adult patients. |
| Therapeutic Class |
COPD Agent |
| Formulation |
Inhalation suspension: 3 mg/2.5 mL aqueous suspension in unit-dose
ampules. |
| MoA |
OHTUVAYRE™ is an inhibitor of the phosphodiesterase 3 (PDE3) and phosphodiesterase 4 (PDE4) enzymes. PDE3 primarily hydrolyzes the second-messenger molecule cAMP but is also capable of hydrolyzing cyclic guanosine monophosphate (cGMP). PDE4 hydrolyzes cAMP only. Inhibition of PDE3 and PDE4 results in accumulation of intracellular levels of cAMP and/or cGMP, resulting in various downstream signaling effects. |
| Dosing and Administration |
Dosing: The recommended dosage of OHTUVAYRE™ is 3 mg (one unit-dose ampule) twice daily, once in the morning and once in the evening, administered by oral inhalation using a standard jet nebulizer with a mouthpiece.
Administration Instructions: First, remove OHTUVAYRE™ unit-dose ampule from foil pouch only immediately before use. Then, shake OHTUVAYRE™ ampule vigorously. Squeeze and completely empty contents of the ampule into the nebulizer cup for administration of OHTUVAYRE™ by oral inhalation. Discard ampule with any residual content. Finally, administer OHTUVAYRE™ by oral inhalation using a standard jet nebulizer equipped with a mouthpiece, connected to an air compressor. |
| Administered by self or by HCP |
Administered by Self |
| Place in Therapy |
Despite maintenance therapy, most COPD patients continue to grapple with daily symptoms such as breathlessness and persistent coughing. With COPD significantly impacting both mortality and morbidity in the US, there has been a lack of innovation in inhaled treatments for over two decades, with new therapies limited to combinations of existing treatment classes. OHTUVAYRE™ offers a much-needed, unique approach as the first inhaled therapy that combines bronchodilator and non-steroidal anti-inflammatory activities in one molecule. As a first-in-class selective dual inhibitor of the enzymes PDE3 and PDE4, OHTUVAYRE™ represents an important advance in the clinical treatment of COPD.
|
| Expected Market Launch Date |
Third quarter of 2024 |
| New Molecular Entity (NME) or Existing Formulation |
Existing Formulation |
| Expected Cost |
Cost unavailable |
| Product Discontinuation |
N/A |
| Clinical Trials |
OHTUVAYRE™ was evaluated in two 24-week clinical trials (ENHANCE-1 and ENHANCE-2) involving 1553 adults with moderate to severe COPD. In ENHANCE-1, 763 patients were randomized to receive either 3 mg of OHTUVAYRE™ or placebo. The mean age was 65 years, with 58% male and 90% White. Patients had a mean smoking history of 41 pack-years, and 25% reported COPD exacerbations within the prior 15 months. At Week 12, OHTUVAYRE™ showed a statistically significant improvement in forced expiratory volume in the first second (FEV1) AUC 0-12h compared to placebo. Morning trough FEV1 improvement was 35 mL (95% CI: 14, 68).
In ENHANCE-2, 790 patients were randomized similarly. The mean age was 65 years, with 52% female and 95% White. The mean smoking history was 42 pack-years, and 21% reported COPD exacerbations within the prior 15 months. At Week 12, OHTUVAYRE™ also demonstrated a statistically significant improvement in FEV1 AUC 0-12h compared to placebo. Morning trough FEV1 improvement was 49 mL (95% CI: 19, 80). However, statistical significance was not achieved in the primary endpoint due to hierarchy testing.
In terms of SGRQ responder rates at Week 24, in ENHANCE-1, 58.2% of patients on OHTUVAYRE™ versus 45.9% on placebo had an improvement of 4 or more points in SGRQ score (OR: 1.49; 95% CI: 1.07, 2.07). In ENHANCE-2, 45.4% on OHTUVAYRE™ versus 50.3% on placebo showed similar improvement (OR: 0.92; 95% CI: 0.66, 1.29).
Overall, OHTUVAYRE™ demonstrated statistically significant improvements in lung function measures in both trials, with varying effects on quality of life as measured by the SGRQ. |
| |
Justia Trademarks. OHTUVAYRE Trademark Information. Available from: https://trademarks.justia.com/984/50/ohtuvayre-98450540.html. Accessed June 26, 2024.
Verona Pharma plc. Verona Pharma Announces US FDA Approval of OHTUVAYRE™ (ensifentrine). Available from: https://www.veronapharma.com/news/verona-pharma-announces-us-fda-approval-of-ohtuvayre-ensifentrine/. Accessed June 26, 2024.
Ohtuvayre HCP. OHTUVAYRE™ (ensifentrine) US Prescribing Information. Available from: https://ohtuvayrehcp.com/files/Ohtuvayre-US-Prescribing-Information.pdf. Accessed June 26, 2024. |