ICER council votes on effectiveness of add-on ensifentrine for COPD

Key takeaways:

• Patient experts expressed excitement over ensifentrine’s ability to lower exacerbations.
• If priced between $7,500 and $12,700 a year, treatment would reach common cost-effectiveness thresholds.

During a Midwest Comparative Effectiveness Public Advisory Council public meeting, 11 of 15 members believed current evidence was adequate in showing the net health benefit of ensifentrine plus maintenance therapy.

Healio previously reported on the evidence report published by Institute for Clinical and Economic Review (ICER) on ensifentrine (Verona Pharma), which found that it yielded multiple benefits in patients with moderate to severe COPD but would exceed typical cost-effectiveness thresholds.

Ensifentrine is a nebulized treatment administered as 3 mg twice a day, according to the ICER evidence report. The FDA is expected to make a regulatory decision on its use by June 26.

Clinical data, cost

ICER’s evidence report considered the use of ensifentrine added to maintenance therapy (LAMA, LABA, combination therapy or combination therapy with inhaled corticosteroids) among adults with moderate to severe COPD vs. maintenance therapy alone.

As Healio previously reported, results from two phase 3 trials (ENHANCE-1 and ENHANCE-2) showed improved measures of lung function, exacerbation rate and quality of life with ensifentrine at 12 or 24 weeks compared with placebo.

The ICER report gave ensifentrine a B+ evidence rating, and this grade indicates that there is high certainty of “at least a small net health benefit, and may result in substantial net health benefit” compared with maintenance therapy alone. David M. Rind, MD, MSc, chief medical officer at ICER, previously told Healio that this rating is “strong ... for a new therapy.”

ICER noted that ensifentrine’s pricing is not yet known, but a placeholder price of $18,000 indicates that it will go over thresholds that traditionally are considered cost-effective in the U.S. market.

According to the report, if ensifentrine was priced between $7,500 and $12,700 a year, it would reach commonly used thresholds.

Voting

During the public meeting, 15 members of the Midwest Comparative Effectiveness Public Advisory Council (CEPAC) body voted on three questions related to ensifentrine and two questions related to COPD.

The first question asked members to consider current evidence and judge whether this information is “adequate to demonstrate that the net health benefit of ensifentrine added to maintenance therapy is superior to that of maintenance therapy alone.”

Before voting, some members expressed concern over the trial’s exclusion of patients on LAMA/LABA therapy or triple therapy since those are common treatments. Steven D. Pearson, MD, MSc, founder and president of ICER, provided some insight into why these patients may have been kept out of the trial.

“Health technology assessment groups run into this problem all the time, where the trial is conceived in an era in which standard of care according to guidelines at the time say x, and in a weird way, they’re almost hardwired into needing to follow that standard of care at that time, even if some clinical experts think that it needs to be kind of updated,” Pearson said.

Timothy J. Wilt, MD, MPH, professor of medicine, core investigator and staff physician at the Minneapolis VA Center for Chronic Disease Outcomes Research, indicated that he was leaning toward no and specifically called attention to the quality of life findings.

“I’m pretty convinced that there is some reduction in exacerbations ... but I’m not finding a really meaningful benefit in quality of life or dyspnea or things like that,” Wilt said. “That, for many patients, is the main driver of why they seek additional therapy.”

From a patient perspective, the exacerbation reduction found with ensifentrine was a major finding.

“As a patient, I got to say, a 40% even possibility of reducing my exacerbations from the one to six I have every year is like a miracle,” Valerie Chang, BA, JD, patient expert, executive director of the Hawaii COPD Coalition and vice chair of the board at COPD Foundation, said. “I have never heard of anything like this.”

“I may only have one or two exacerbations each year, but if it takes me 3 to 6 months to recover from one, that is a significant burden on my quality of life,” Phyllis DiLorenzo, patient expert and COPD Foundation board member, said.

In the end, 11 members believed that the clinical evidence presented was adequate, whereas four members did not.

Switching to a focus on COPD rather than on ensifentrine, the Midwest CEPAC body was asked whether they agree or disagree with the statement, “there is substantial unmet need despite currently available treatments,” on a 5-point scale.

Prior to the vote, Chang highlighted the importance of a new therapy for patients with COPD.

“I’ve had every side effect imaginable ... but I’m really excited about a new therapy that could possibly have fewer side effects because we have to keep tweaking, and some of us are in these therapies for decades,” she said.

DiLorenzo added that ensifentrine has the potential to be a “game changer” in the COPD space.

“The amount of exacerbations that could be reduced for us would greatly reduce the stress on families, on economics [and] on quality of life,” she said.

After listening to these comments, the majority either agreed (n = 9) or strongly agreed (n = 4) that there is an unmet need. The remaining two members disagreed.

The next question also centered on COPD. Members were asked if they agreed or disagreed with the statement, “this condition is of substantial relevance for people from a racial/ethnic group that have not been equitably served by the health care system.”

Importantly, Grace Lin, MD, medical director for health technology assessment at ICER, noted that 92% of individuals in the trials assessing ensifentrine were white, and there were “very few, if any” American Indians and Alaska Natives when asked about representation.

During this discussion, Stephanie Christenson, MD, MAS, associate professor in the division of pulmonary, critical care, allergy and sleep medicine at University of San Francisco, brought up that spirometry is required to diagnose someone with COPD.

“To even get a diagnosis of COPD requires that you have access to testing and so ... in countries where that’s lower, you’re going to have lower prevalence of the diagnosis,” she said.

In the end, eight members agreed with the statement, two strongly agreed and five were neutral.

The last two questions the CEPAC body voted on centered around ensifentrine.

Similar to the above format, members used a 5-point scale to express whether they agreed or disagreed with this statement, “based on the relative effects of ensifentrine added to maintenance therapy vs. maintenance therapy alone: The treatment is likely to produce substantial improvement in caregivers’ quality of life and/or ability to pursue their own education, work and family life.”

Chang started the discussion by talking about how her husband is her caregiver.

“When I was 42 and we had two young children, every time I got an exacerbation, the world kind of stopped for me, and so [my husband] had to pick up all the slack,” she said.

DiLorenzo also highlighted the wide impact COPD has on those around the patient.

“I’m fortunate in that my partner is a retired EMS paramedic,” she said. “However, most of my peers do not have a medical professional as a spouse or partner, so it can be very scary for a caregiver. It increases the burden on their mental health, and their mental health transfers over to the patient.”

After hearing from the two patient experts and considering the results from the clinical trials, most members felt neutral about the statement (n = 10). Of the remaining members, three agreed and two disagreed.

Lastly, members discussed whether “the treatment offers a substantial opportunity to improve access to effective treatment by means of its mechanism of action or method of deliver.”

Juan C. Rojas, MD, MS, director of clinical informatics and data science and assistant professor in the department of internal medicine at Rush University, noted that this nebulized therapy could be of great help to patients with hand arthritis.

“I think for those patients who have specifically either a combination of cognitive issues that could lead them to have trouble using a dry powder inhaler and/or dexterity issues ... this could be an option for caregivers to sort of be the facilitator to put the solution into the machine and then allow [the patient] to take that therapy daily,” Rojas said.

“There is a small, but not insignificant, patient population that would benefit from this new inhaled nebulized therapy that doesn’t currently exist,” he added.

As a patient expert, Chang provided some insight on struggles patients face with treatments and what they are willing to do if it means they experience fewer exacerbations.

“I think it’s underestimated how much medicine that patients get on the carpet or in the air when they have poor coordination or dementia as they age,” she said.

“Even though it’s a slight inconvenience to use a nebulizer, I’m happy to use it if I know it’s going to help possibly reduce my rate of exacerbations, and I think a lot of patients are in that category, especially when they’re already having a very low inspiratory flow, so they have a hard time getting all the medicine where it should go,” Chang added.

In contrast, Wilt said he did not see ensifentrine as offering a “substantial opportunity.”

“Mechanism of action doesn’t influence me too much,” he said. “I want to know whether something works, and the fact of the matter is in this situation, many of the patients were not on optimal therapy. I think that there may be marginal areas, but I don’t see it rising to the level of substantial.”

In this final vote, eight members felt “neutral” about the statement, four members disagreed and three agreed.

Importantly, a question on the long-term value for money of ensifentrine added to maintenance therapy vs. maintenance therapy alone was not voted on because no price has been given for ensifentrine.

References:

• ICER. Ensifentrine for the treatment of chronic obstructive pulmonary disease: Effectiveness and value. Public Meeting of the Midwest CEPAC. June 14, 2024.
• Institute for Clinical and Economic Review publishes evidence report on treatment for chronic obstructive pulmonary disease. https://icer.org/news-insights/press-releases/institute-for-clinical-and-economic-review-publishes-evidence-report-on-treatment-for-chronic-obstructive-pulmonary-disease/. Published May 30, 2024. Accessed June 14, 2024.
• Lin GA, et al. Ensifentrine for the treatment of chronic obstructive pulmonary disease: Effectiveness and value. Institute for Clinical and Economic Review. 2024.