Nuance Pharma Announces Ensifentrine Meets Primary Endpoint in Phase 3 ENHANCE-CHINA Trial for COPD

Statistically significant improvements in lung function

Consistent trends of quality of life and exacerbation rate reduction as ENHANCE-1/2

Well tolerated safety profile

NDA submission planned for 2H 2025

SHANGHAI,May 16, 2025/PRNewswire/ -- Nuance Pharma ("Nuance") today announces its top-line Phase 3 ENHANCE-CHINA(NCT05743075) trial results evaluating nebulized ensifentrine for the maintenance treatment of chronic obstructive pulmonary disease ("COPD"). The ENHANCE-CHINAtrial has successfully met its primary endpoint, as well as secondary endpoints demonstrating improvements in lung function.

The investigational study drug, ensifentrine is a first-in-class selective dual inhibitor of phosphodiesterase 3 and 4 ("PDE3; PDE4") that combines bronchodilator and non-steroidal anti-inflammatory effects in one molecule, delivered directly to the lungs through a standard jet nebulizer without the need for high inspiratory flow rates or complex hand-breath coordination.

Highlights

- Study population (n = 526 randomized):

• Subject demographics and disease characteristics were well balanced between treatment groups
• Approximately 46% of subjects received background COPD therapy, either a long-acting muscarinic antagonist ("LAMA") or a long-acting beta-agonist ("LABA"). Additionally, approximately 38% of all subjects received inhaled corticosteroids ("ICS") with concomitant LABA.

- Primary endpoint met (FEV₁AUC 0-12hr):

• Placebo corrected, change from baseline in average FEV₁area under the curve 0-12 hours post dose at week 12 was 110 mL (p<0.0001) for ensifentrine
• Statistically significant and clinically meaningful improvements with ensifentrine demonstrated across key subgroups including age, smoking status, COPD severity, background medication, ICS use, chronic bronchitis, FEV₁reversibility

- Secondary endpoints of lung function:

• Placebo corrected, increase in peak FEV₁of 174 mL (p<0.0001) at week 12
• Placebo corrected, increase in morning trough FEV₁of 36 ml (p=0.0533) and evening trough FEV₁of 65 ml (p=0.0038) at week 12, confirming twice daily dosing regimen.
• Placebo corrected, increase in average FEV₁of 162 ml (p<0.0001) 0-4 hours post dose and 77 mL (p=0.0003) 6-12 hours post dose at week 12

- COPD symptoms and quality of life (QoL):

• Clinically meaningful improvements in dyspnea as measured by Transition Dyspnea Index (TDI) in the ensifentrine group were observed at all weeks (6, 12 and 24) with a statistically significant improvement of 0.8 unit compared to placebo at week 24.
• Quality of Life (QoL) as measured by St George's Respiratory Questionnaire (SGRQ) Total Score in the ensifentrine group improved from baseline to greater than the MCID of -4 units with a significant improvement of -2.9 units compared to placebo at week 24.
• Daily symptoms as measured by Evaluating Respiratory Symptoms (E-RS) Total Score in ensifentrine group showed improvement from baseline as early as 6 weeks and continued improvement at 12 and 24 weeks, numerically exceeding placebo at each measurement. 

- Exacerbation rate reduced

• Subjects receiving ensifentrine demonstrated a 28% reduction in the rate of moderate/severe COPD exacerbations over 24 weeks compared to those receiving placebo (RR = 0.72, 95% CI: (0.43, 1.22))
• Treatment with ensifentrine significantly decreased the risk of a moderate/severe exacerbation as measured by time to first exacerbation when compared with placebo by 25% (HR = 0.75, 95% CI: (0.44, 1.28))

- Favorable safety profile:

• Ensifentrine was well-tolerated with treatment related AE incidence similar to placebo

Mark Lotter, founder and Chief Executive Officer of Nuance Pharma, said:"We are very pleased by the successful outcome of our Phase 3 ENHANCE-CHINAstudy, bringining us another step closer to providing a much needed novel therapy for COPD patients inChina. These promising results demonstrate ensifentrine's strength as a first-in-class bronchodilator and non-steroidal anti-inflammatory therapy for COPD, as an advance to existing treatment options. We plan to submit a New Drug Application to the China NMPA in the second half of 2025. We would like to thank all the patients and investigators for their participation in the ENHANCE-CHINAprogram."

Charlie Chen, Chief Operating Officer of Nuance Pharma added:"The totality of ENHANCE data including improvements in lung function, symptoms, quality of life measure and reduction in exacerbations, coupled with favorable safety profile, support our belief that ensifentrine will change the treatment paradigm for COPD. Following our ongoing early access programs in Hainan BoAo and Greater Bay Area, as well as regulatory approval inMacau, we look forward to bringing this medicine to patients inGreater China."

David Zaccardelli, Pharm. D., President and Chief Executive Officer of Verona Pharma, said:"we look forward to Nuance Pharma's continued progress and having Ohtuvayre® available for the millions of symptomatic patients needing additional treatment."

Nuance Pharma plans to release additional information from ENHANCE-CHINAat upcoming scientific conferences.

InFeb 2025, the Pharmaceutical Administration Bureau Macau approved Ohtuvayre™ (ensifentrine) for the maintenance treatment of COPD in adult patients. InNov 2024, Nuance Pharma launched Ohtuvayre™ inChina'sHainan Boao Pilot Zone through early access program. InSep 2024, Nuance Pharma completed recruitment for ENHANCE-CHINA, the phase 3 clinical trial of Ohtuvayre™ (ensifentrine) for the maintenance treatment of COPD.

InJune 2024, Nuance Pharma's global partner Verona Pharma plc (Nasdaq: VRNA), announced the US Food and Drug Administration ("FDA") approved Ohtuvayre™ (ensifentrine) for the maintenance treatment of COPD in adult patients.

In 2021, Nuance Pharma entered into an agreement with Verona Pharma for the exclusive rights to develop and commercialize Ohtuvayre™ (ensifentrine) inGreater China(mainlandChina,Hong Kong,MacauandTaiwan).

About Ohtuvayre™(ensifentrine)

Ohtuvayre™ is the first inhaled therapy for the maintenance treatment of COPD that combines bronchodilator and non-steroidal anti-inflammatory activities in one molecule. Verona has evaluated nebulized Ohtuvayre™ in its Phase 3 clinical program ENHANCE ("Ensifentrine as a Novel inHAled Nebulized COPD thErapy") for COPD maintenance treatment. Ohtuvayre™ met the primary endpoint in both ENHANCE-1 and ENHANCE-2, demonstrating statistically significant and clinically meaningful improvements in lung function.

About the ENHANCE-CHINAprogram

The randomized, double-blind, placebo-controlled study evaluate the efficacy and safety of nebulized ensifentrine as monotherapy and added onto a single bronchodilator, either a LAMA or a LABA, compared to placebo, and subjects may receive ICS.

Patient Population: 526 moderate to severe, symptomatic, COPD patients at 46 sites inChina.

Dose/Duration: subjects were randomized to receive a 3mg nebulized dose of ensifentrine or nebulized placebo twice daily for 24 weeks

Primary Endpoint: Improvement in lung function with ensifentrine as measured by average FEV₁AUC 0-12 hours post dose at week 12.

Secondary Endpoints: lung function endpoints including peak and morning trough FEV₁, COPD symptoms and health related quality of life through 24 weeks via SGRQ and E-RS, and exacerbation at 24 weeks, and others

Safety: Assessed over 24 weeks

Further information about ENHANCE-CHINAprogram can be found atwww.clinicaltrials.gov(NCT05743075)

About Verona Pharma

Verona Pharma is a biopharmaceutical company focused on developing and commercializing innovative therapies for the treatment of chronic respiratory diseases with significant unmet medical needs. Ohtuvayre™ (ensifentrine) is the Company's first commercial product and the first inhaled therapy for the maintenance treatment of COPD that combines bronchodilator and non-steroidal anti-inflammatory activities in one molecule. Ohtuvayre™ (ensifentrine) has potential applications in non-cystic fibrosis bronchiectasis, cystic fibrosis, asthma and other respiratory diseases. For more information, please visitwww.veronapharma.com. 

About Nuance Pharma

Nuance Pharma is an innovation focused biopharmaceutical company, with both late-stage clinical pipeline and commercial stage asset portfolio. Focusing on specialty care, Nuance has established a differentiated combination of commercialized assets and innovative pipeline across respiratory, pain management, emergency care and iron deficiency anemia. With the mission to address critical unmet medical needs inAsia Pacific, Nuance deploys the Dual Wheel model that develops a global leading innovative pipeline, while maintaining a self-sustainable commercial operation in bothChinaandAsiaas a region. For more information, please visitwww.nuancepharma.com. 

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SOURCE Nuance Pharma Limited