New drug for severe asthma 'shows massive promise'

Monday August 8 2016

"Asthma drug 'gamechanger' could revolutionise treatment," The Guardian reports after a new drug called fevipiprant showed promising results in a small study of 61 people with moderate to severe asthma.

Asthma is a lung condition that can cause inflammation of the airways, which can lead to breathing difficulties.

While many people can control the condition with existing drugs, a minority of people only have a partial response to treatment, so their quality of life can be adversely affected.

This trial aimed to investigate whether fevipiprant reduced airway inflammation in people with moderate to severe asthma associated with raised levels of eosinophils, the particular white blood cell linked to asthma.

The 12-week trial compared fevipiprant with placebo in 61 adults. The drug was added to any medication they were already taking.

The main outcome was on the percentage of eosinophils in their sputum, which did decrease by a greater amount in the fevipiprant group. It also had a beneficial effect on quality of life, but no effect on overall asthma control or symptoms.

The potential implications of the research were summed up succinctly by Dr Samantha Walker, Director of Research and Policy at Asthma UK, who said: "This research shows massive promise and should be greeted with cautious optimism."

These initial findings are promising, but more studies will be needed to confirm that the drug is safe and has a definite effect on asthma control compared with other treatments.

Where did the story come from?

The study was carried out by researchers from a variety of institutions, including the University of Leicester and the University of Oxford in the UK, and Novartis in Switzerland.

It was jointly funded by the UK National Institute for Health Research, the EU AirPROM project, and Novartis Pharmaceuticals, the Swiss drug company behind fevipiprant.

Industry funding is not unusual, but four of the researchers were employed by Novartis. This represents a potential conflict of interest that was clearly stated in the study.

The study was published in the peer-reviewed journal, The Lancet – Respiratory Medicine.

This study was widely reported on by the press. While the coverage was generally accurate, much of it was arguably overoptimistic.

Claims that fevipiprant is a "wonder drug" that could mark "the end of the inhaler" verge on hype. Cautious optimism is probably a better approach.

What kind of research was this?

This randomised controlled trial (RCT) aimed to investigate whether fevipiprant (currently unlicensed in the UK) reduced inflammation in patients with moderate to severe eosinophilic asthma.

This is asthma characterised by increased levels of eosinophils – the particular type of white blood cell known to be associated with asthma and allergies. White blood cells are used by the immune system to combat infections.

There are currently 5.4 million individuals receiving asthma treatment in the UK alone, representing a large burden on the NHS.

A double-blind placebo-controlled trial like this one is one of the best ways of investigating the safety and effectiveness of a potential new treatment. However, several stages of testing can be needed before we know whether this could lead to a new licensed treatment

What did the research involve?

The trial was carried out at Glenfield Hospital in Leicester in the UK, and involved 61 patients (mean age 50) with persistent moderate to severe asthma and an increased sputum eosinophil count (more than 2%). Individuals with other serious coexisting conditions were excluded.

Between 2012 and 2013, the participants were randomly assigned (1:1) to receive either fevipiprant tablets or a placebo for 12 weeks. Thirty individuals were given fevipiprant (225mg twice a day) and 31 were given the placebo.

Fevipiprant was added to any medication participants were already taking. The two groups were matched for baseline characteristics.

Patients had a variety of measurements taken at the start of the study, including eosinophil sputum count, scores on the Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ), and FEV1, the amount of air that can be forcibly exhaled in the first second of breathing out. Patients were assessed again at weeks 6 and 12.

The main outcome of interest was changes in sputum eosinophil levels between the start and end of treatment. Changes in asthma symptoms and FEV1 were compared, and the safety and tolerability of the drug was also assessed throughout the trial.

What were the basic results?

Fevipiprant gave greater reduction in eosinophil count compared with placebo. In the fevipiprant group, the mean percentage of eosinophils in sputum decreased 4.5 times from 5.4% to 1.1%. It decreased by only 1.3 times in the placebo group from 4.6% to 3.9%.

The difference between groups was statistically significant (3.5 times greater reduction, 95% confidence interval [CI] 1.7 to 7.0).

Looking at other outcomes, fevipiprant had no significant effect on asthma symptoms. In the fevipiprant group, the symptom score decreased by a mean 0.18 points (95% CI -0.54 to 0.18) and in the placebo group it increased by a mean 0.14 points (95% CI -0.22 to 0.49). This made a non-significant 0.32-point reduction with treatment (95% CI -0.78 to 0.14).

The change in quality of life score on the AQLQ was thought significant. In the fevipiprant group, it increased by 0.27 points (95% CI -0.07 to 0.61) between week 0 and week 12, and decreased by 0.33 points (95% CI -0.06 to 0.01) in the placebo group. This was a significant 0.59-point increase with treatment (95% CI 0.16 to 1.03).

Treatment also significantly improved FEV1, with a difference between the groups of a 0.16 litre increase (95% CI 0.03 to 0.30).

Overall, fevipiprant had a favourable safety profile – no deaths or serious adverse events were reported in the group.

Three patients in the fevipiprant group and four in the placebo group withdrew from the study because of asthma complications, but these were not judged to be related to the study drug.

How did the researchers interpret the results?

The researchers concluded that, "Compared with placebo, fevipiprant significantly reduced eosinophilic inflammation in the sputum and bronchial submucosa in patients with persistent moderate to severe asthma and sputum eosinophilia.

"Fevipiprant reduces eosinophilic airway inflammation and is well tolerated in patients." 

Conclusion

This study aimed to investigate whether the new drug fevipiprant reduced inflammation in patients with moderate to severe eosinophilic asthma.

It found the drug had a significant effect on the main outcome being studied – compared with the placebo group, the mean percentage of eosinophils in sputum decreased by a greater percentage in the fevipiprant group.

It also gave improvements in asthma quality of life and FEV1, though the drug didn't have a significant effect on overall asthma control.

Although these findings show potential promise for the future, there are a few points to bear in mind:

  • The trial had a small sample size of 61 patients and only a 12-week testing period. Longer follow-up would be ideal to test whether the drug remained efficient and complication-free in the long-term.
  • The mean age of participants was 50, and the study did not look at the effects in children or young people aged under 25.
  • The researchers only compared the drug with placebo and not other active treatment, though people in both groups continued to take their standard asthma treatments.
  • The main outcome the study was designed to assess was the effect on eosinophil numbers, not asthma symptoms or asthma control. This means it doesn't provide strong evidence at this stage that the treatment wouldn't definitely improve a person's day-to-day symptoms and reduce the risk of asthma attacks.

Dr Samantha Walker, Director of Research and Policy at Asthma UK commented: "More research is needed and we're a long way off seeing a pill for asthma being made available over the pharmacy counter, but it's an exciting development and one which, in the long term, could offer a real alternative to current treatments."

She also noted that this finding should be "greeted with cautious optimism".

Read more about living with asthma. You can also join the HealthUnlocked online forum, where you can connect with other people living with asthma.  

Analysis by Bazian
Edited by NHS Website