Q&A: Discussing ensifentrine for COPD ahead of FDA decision

Key takeaways:

• Ensifentrine had favorable efficacy and safety profiles in two phase 3 trials.
• Verona Pharma is prepared for launch upon FDA approval.

The FDA is expected to make a decision on ensifentrine to treat patients with COPD by June 26.

As Healio previously reported, the global, multicenter, randomized, double-blind, parallel-group, placebo-controlled phase 3 ENHANCE-1 and ENHANCE-2 trials found that patients with COPD receiving ensifentrine (Verona Pharma) showed improved measures of lung function, quality of life and exacerbation rate over 12 or 24 weeks.

Ensifentrine for 24 weeks has also been shown to improve dyspnea in patients with moderate to severe COPD.

Ahead of the FDA decision, Healio spoke with David Zaccardelli, PharmD, president and CEO of Verona, and Chris Martin, chief commercial officer of Verona, to learn more about the drug, how it is unique and expected next steps upon approval.

Healio: What do current maintenance COPD treatments look like? How do patients with COPD feel about these options?

Zaccardelli: COPD is a chronic, progressive disease, so patients ultimately need support on a chronic basis. Treatment has traditionally been with either a long-acting muscarinic antagonist, a long-acting beta agonist or inhaled corticosteroids. Treatment of COPD has been grounded in these three pharmacologic classes to support the patient by helping them breathe easier, feel better and reduce exacerbation rates. None of those are cures; they are all symptomatic treatments.

The current therapy has been those products given individually or in combination. Historically, innovation has been just to give those three classes of drugs in different ways, different devices, etc. That’s been going on for pretty much the last several decades.

Chris Martin

Martin: From a patient perspective, there’s a variety of research out there. A good study was done in 2022 from Phreesia that looked at how patients feel with their current treatments. It showed about 50% of these patients are having symptoms for 24 to 30 days a month despite current treatments. The symptom burden and the day-to-day burden is very high with these patients.

When we talk to patients in research today, they are looking for new ways to get back to simple things in their daily life. Things that probably you and I take for granted, such as walking outside to the mailbox, walking a dog and playing with a grandchild. Those are things that have been taken away from them, and those simple things are what they’re looking for treatments to help them get back to. That’s where something novel like ensifentrine we hope can help many of these patients.

Healio: What should clinicians know about ensifentrine? How is it different/unique from other COPD treatments?

Zaccardelli: Ensifentrine brings a novel mechanism of action, which has really been needed to help and support patients with COPD.

With ensifentrine as a phosphodiesterase enzyme 3 and 4 (PDE3 and PDE4) inhibitor, approaching the treatment from this different mechanism improves lung function/helps patients breathe better. It also improves their symptoms, makes them feel better, enables them to do more and reduces exacerbation rate and risk.

These outcomes in the clinical trials occurred either in patients who are not receiving any background therapy or in patients who are receiving other therapies, such as a LAMA, LABA or a LABA-ICS primarily.

It’s a treatment that can work across a wide spectrum of patients, and this type of treatment has never been available before for physicians and patients.

If approved, physicians will have a drug that is a bronchodilator and a nonsteroidal anti-inflammatory by the inhalation route. They’re able to get anti-inflammatory activity without using a steroid for the first time, and I believe that is going to fundamentally change how COPD is treated. This element is a bit underappreciated, but as ensifentrine gets integrated into the treatment paradigm, I think health care providers will prescribe it and not give inhaled steroids as often as they currently are prescribing.

Healio: Are there any specific COPD patients the drug targets (eg, age, severity, failure of other treatments, etc)?

Zaccardelli: Although it is a broadly applicable drug, if approved, we really look at it for those patients who remain symptomatic, who may be on other treatments and still have symptoms. As Chris mentioned, approximately half of the 8.6 million patients on current maintenance treatment for COPD are experiencing symptoms. We believe ensifentrine can help those patients who are currently symptomatic.

Healio: Why should the FDA approve ensifentrine? How has it been shown to benefit patients with COPD?

Zaccardelli: Ensifentrine has a compelling benefit to risk profile. The benefit that it provides, improving lung function, improving symptoms, improving quality of life and reducing exacerbation rate and risk, is an incredibly strong efficacy profile. When combined with its safety profile, that’s very favorable. The adverse experiences are generally comparable with placebo.

When you have a very efficacious drug with a favorable safety profile, that gives you a compelling benefit to risk profile, and that is the underpinning and why the FDA is expected to approve ensifentrine.

Healio: An Institute for Clinical and Economic Review (ICER) evidence report found that ensifentrine would exceed typical cost-effective thresholds if priced at $18,000 a year. Do you have any thoughts on this finding?

Zaccardelli: A broad thing to keep in mind is that ICER approaches their evaluation using certain models and techniques that don’t necessarily take everything into consideration. There’s a lot of debate in pharmacoeconomic models. I think that while ICER is a body with a certain opinion, when you look at it more broadly, you’ll see that there are other models that come up with different economic analyses for different drugs, including ensifentrine.

Martin: ICER looks at economic modeling in one way. There are a variety of different models you can look at to assess how drugs get priced at launch to when they become generic.

The impact of improving someone’s day-to-day activities that have been taken away from them is something that is hard to put a value on in a model.

Certain models place greater emphasis on that than others. If you evaluate health care costs and exacerbations, you may get one answer. If you bring in the impact of quality of life and the way that the drug price changes over time, you get another answer.

We believe the value that ensifentrine would bring is great to the health care system and to the patients that are affected by COPD.

COPD in general is about $50 billion a year in direct and indirect costs for patients in the U.S. health system today. Further, a single exacerbation is almost $25,000 to $30,000 in cost. Being able to help these patients from a symptomatology, an exacerbation rate and risk reduction provides tremendous value to not only the patient and their day-to-day living but also to the health care system.

Healio: What would be the next steps after ensifentrine receives FDA approval?

Martin: We’ve been preparing for launch for the last 18 to 24 months. One of the benefits the organization has had is to be properly financed to do the right work before launch. Some of that included disease education work around the symptoms that these patients face in the Unspoken COPD campaign that launched at ATS 2023. The goal was to highlight the burden of symptoms and to encourage physicians and patients to talk a little bit more about what they’re dealing with and how those symptoms are affecting their day-to-day lives. That work has set us up really well for launch.

Upon approval, we would finalize some key manufacturing components to get the drug in the channel. We believe the product will be in the channel very rapidly after approval.

From a commercial side, we are preparing and are prepared to have our reps in place at/around approval.

At that point, they would be focused on about 15,000 physicians who we believe are the most important. We know symptomatic patients move from primary care into pulmonology, so those 15,000 physicians tend to be more pulmonology-focused, nurse practitioners and PAs in pulmonology offices and some primary care. We believe we’re in a very good position there from a rep and a field facing standpoint.

From a market access standpoint, we’ve completed all our clinical and major reviews with the payers. Because ensifentrine is delivered through a nebulizer, it gets reimbursed under a different channel than typical COPD drugs. It gets reimbursed under medical benefit.

We’ll launch with a nonspecific J code, and our plan is to submit our product-specific J code and local coverage determination by June 28, assuming approval comes on June 26 or before. That puts us in a good place to have a functioning product specific J code at the beginning of 2025.

Healio: If the drug does not receive FDA approval, what are your plans?

Zaccardelli: This outcome is not our expectation, but with that said, we would want to understand the agency’s position, what items need to be addressed and then go from there.

References:

• Patients in focus: COPD treatment and perceptions. https://lifesciences.phreesia.com/reports/patients-in-focus-copd-treatment-and-perceptions/. Accessed: June 12, 2024.
• Verona Pharma announces the US FDA has accepted the new drug application filing for ensifentrine for the maintenance treatment of COPD. https://www.veronapharma.com/news/verona-pharma-announces-the-us-fda-has-accepted-the-new-drug-application-filing-for-ensifentrine-for-the-maintenance-treatment-of-copd/. Published Sept. 11, 2023. Accessed June 11, 2024.