P492 –New TQT Analysis by Verona Pharma supports planned NDA Submission

Verona Pharma New TQT Analysis : P492

6 June, 2022 | DelveInsight

There were approximately 30,701,523 diagnosed prevalent cases of COPD in the 7MM (The USA, EU5, Japan) in 2018. According to DelveInsight, this number is expected to grow to 37,458,566 in 2030.  Although there are effective therapies for the management of the disease, the progression of the disease continues to be a problem.Treatment objectives are focused on relieving symptoms and reducing the risk of future exacerbations. Current rescue COPD treatments get limited to three mechanisms of action (MOAs) and their combinations i.e., bronchodilators long-acting muscarinic agent (LAMA), long-acting beta-adrenoceptor agonist (LABA), and anti-inflammatory inhaled corticosteroids (ICS). The following MOAs are also available in double and triple combination therapies (LABA + ICS; LABA + LAMA; and LABA + LAMA + ICS).

Moreover, COPD has been under-diagnosed and under-treated, with treatments prescribed contrary to guidelines in patients according to their symptoms and risk level.

Two phosphodiesterase-4 inhibitors (PDE-4) inhibitors are under development for COPD, i.e., Ensifentrine (RPL554) and CHF6001/Tanimilast for COPD. PDE-4 inhibition has an established role in the management of COPD as earlier Roflumilast, a PDE-4, proved an alternative approach to prevent exacerbations in chronic bronchitis and a history of prior exacerbations. The PDE-4 as an overall approach was praised for its personalized basis but many of the recommendations were not strictly evidence-based.

Ensifentrine is a novel molecule, having both bronchodilator and anti-inflammatory properties. The drug is simultaneously being developed as an inhaled medicine, making it a potential option for COPD patients who use hand-held devices in the US. Other than that, ensifentrine has the potential to be an effective treatment for other respiratory diseases, including asthma and cystic fibrosis. Verona Pharma is developing ensifentrine in three formulations for the most widely used inhalation devices: nebulizer, dry powder inhaler (DPI), and pressurized metered-dose inhaler (pMDI).

Verona Pharma presented an abstract demonstrating that ensifentrine met all safety objectives in a through QT (TQT) study at the American Thoracic Society International Conference (ATS) 2022. Before the company could move to the filing process for the drug, the FDA required a TQT study for New Drug Application.

The detailed results of the same study were published earlier in December 2021, demonstrating the effectiveness and no clinically relevant effects related to cardiac conduction including QTcF, PR and QRS intervals in any 3 mg or 9 mg inhaled dosage of ensifentrine dose. Among 32 participants in the study, nearly 14 reported AEs, including 13 TEAEs of which one was serious as the subject had physical injuries due to a syncope event and was positive for COVID-19 (moderate). The data supported the ongoing two-phase III ENHANCE trials. The company expects the top-line data from both ENHANCE-1 and ENHANCE-2 trials in 2022.

The current abstract presented at ATS 2022 has made the way clear for the commercialization of the drug following the successful completion of the phase III trials. 

According to the company, this molecule has been through 16 clinical trials for COPD, and its novel approach has shown clinical benefit while eliciting no side effects. However, the path for Ensifentrine was not this smooth, it had a setback when a phase II clinical trial failed attributed to poor design. Verona had lost its shares in the market, but the appointment of the new CEO and the trust of investors led to the conduction of the large phase III trials to demonstrate the clinical benefits of the drug.

It is also worth noting that many PDE-3/4 inhibitors have failed previously in early phases showing low therapeutic effects whereas Verona was able to reach the late stages of development while showing the synergistic effect of the drug with other muscarinic antagonists and bronchodilators. 

If approved, Ensifentrine would be able to substitute tiotropium as second-line therapy. We at DelveInsight expect commercialization of ensifentrine in 2024, and the drug to have a decent market share at its peak based on promising efficacy and decent safety profile to date.

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