Two experimental bacteria-based vaccines with very different modes of action have sparked excitement at this year’s ERS Congress, with both showing strong promise in reducing COPD exacerbations despite mixed clinical trial results.
The performance of the mucosal bacterial vaccine MV130 was described by one expert as being “so impressive” it was almost “too good to be true”. And while a vaccine developed by GlaxoSmithKline targeting two specific bacteria failed to hit primary targets, the researchers say the data indicates potential that warrants further investigation.
Professor Luis Puente Maestu, from the Hospital General Universitario Gregorio Marañón in Madrid, Spain, led a Phase III trial assessing the clinical efficacy and safety of MV130 – an immunotherapy primarily containing heat-inactivated Streptococcus pneumonia and Staphylococcus aureus and epidermis – in patients with COPD.
The immonotherapy is based on the premise that certain microbial stimuli acting on innate immune cells can promote long-lasting nonspecific protection against different pathogens, a phenomenon termed trained immunity.
In the trial, participants were randomised to receive either the immunotherapy (97) or a placebo (101) at two puffs per day, for up to 12 months, and were then followed up for a further 6 months.
The researchers found that therapeutic immunomodulation with MV130 significantly cut the number of exacerbations, the length of exacerbations and the use of antibiotics in COPD patients during the 18 months of the study.
MV130 drove down acute exacerbations by 30% compared to placebo, with the greatest reduction seen in the number of severe exacerbations (32 versus 70, respectively). A reduction in moderate exacerbations was also observed (177 versus 229), but not for mild exacerbations (32 versus 30).
MV130 also decreased the duration of exacerbations by 50% compared to placebo (median number of days 10 versus 20, respectively) and antibiotic use by 60% (12 versus 29 consumption days).
Also, on the safety side, just two drug related systemic adverse events were reported during 18 months: one in the placebo group (urticaria) and one in the treatment group (cutaneous itching), indicating that MV130 is safe to use in COPD patients, Prof Puente Maestu said.
Commenting on the findings, Professor Guy Brusselle, Chair of the European Respiratory Society (ERS) Science Council said they were “very impressive” and “possibly too good to be true”.
However, he also highlighted similar results from a recently published paper showing that MV130 significantly cut the number and duration of wheezing attacks in very young children, as well as the time to first wheezing attack, which further highlights the potential of the immunotherapy vaccine approach.
GSK vaccine fails on primary outcome but impresses nonetheless
Professor Stefan Andreas, from the University of Göttingen, Germany, presented data from a Phase IIb trial assessing a vaccine developed by GlaxoSmithKline designed to reduce bacterial load by targeting two bacteria commonly associated with acute COPD exacerbations (AECOPD) – Haemophilius influenzae and Moraxella catarrhalis>.
In the placebo-controlled trial, 606 COPD patients who had experienced at least one moderate or severe AECOPD in the prior 12 months were randomised to receive either two doses of the vaccine or a placebo shot, with a follow-up period of twelve months. Sputum and blood samples were collected for assessment of immunogenicity, with quantitative PCR testing used to detect bacteria in the sputum.
The vaccine failed to hit its primary target of reducing the number of moderate and severe exacerbations one year after the end of the vaccination period. However, there was a strong trend (p value 0.07) towards a reduction of severe exacerbations, and the vaccination showed an increase in immunogenicity, Prof Andreas told delegates. Also, there were fewer deaths in the vaccine group compared to placebo (10 versus 1, respectively), which might warrant further investigation, he said.
Professor Jadwiga Wedzicha, from Imperial College London, said she was excited about the vaccine’s potential but was not surprised that the study failed on the primary endpoint as it was underpowered. “I think the vaccine works very well…There was a really interesting and important reduction in severe exacerbations and hospital admissions, which suggests that [it] will work in the more severe group … The numbers, however, are small.”
Researchers should now look at the vaccine’s efficacy in reducing COPD exacerbations specifically in patients colonised with Haemophilius influenzae and Moraxella catarrhalis, Prof Wedzicha noted. Also, the vaccine should be assessed as a means to prevent colonisation of these bacteria at an earlier stage, which would be the “holy grail” of this treatment approach, she said.