UK Prix Galien: Astellas C. diff drug on innovation shortlist

This article is the first in a series investigating some of the shortlisted products in the prestigious UK Prix Galien awards, and their potential impact on health services. Prior to the announcement of the winners on 1st October, we look at Astellas' Clostridium difficile therapy Dificlir.

Background
Since its establishment in France in 1970, the Prix Galien award has expanded its reach internationally. Originally created by pharmacist Roland Mehl, its aim is to promote significant advances in pharmaceutical research. He brought together an eminent jury of clinicians, toxicologists, pharmacologists and pharmacists to select and honour the most important drugs introduced to the public market and the most significant research teams in the pharmaceutical field – a practice that continues today.

Now, the Prix Galien takes place across Europe and Canada and is the most prestigious award of its kind in 11 countries.

This year's UK Prix Galien award finalists include a number of candidates which - in addition to impressive clinical credentials - also promise to tackle some important public health issues. In total, 12 companies have reached the finals and will compete across two categories. Therapies for multiple sclerosis, Clostridium difficile, prostate cancer, hepatic encephalopathy, vitreomacular traction, meningococcal Group B and alcohol consumption are competing for the Innovative Drug Award.

Meanwhile, treatments for pulmonary hypertension, and chronic thromboembolic pulmonary hypertension, cystic fibrosis, idiopathic pulmonary fibrosis and multiple myeloma will contest the Orphan Drug Award. See the full details here.

The UK Prix Galien 2014 judging panel is chaired by Professor Sir Michael Rawlins, President of the Royal Society of Medicine, and previously the founding chairman of the National Institute for Health and Care Excellence (NICE) from 1999 to 2013, and co-chaired by Prof Parveen Kumar, President of the Royal Society of Medicine.

Also on the panel are Dr Jane Adam, Dr Amanda Adler, Prof Sir Gordon Duff, Professor Deirdre Kelly, Dr Mark Porter, Prof Sir Mike Richards, Prof Philip Routledge, Prof Simon Thomas and Prof David Webb.

Astellas' Dificlir
Health services in the UK and round the world are continuing to struggle with hospital-acquired infections caused by Clostridium difficile.

A few days ago, data released by the UK's Office for National Statistics (ONS) revealed an increase in deaths caused by the bacterium last year in Wales, reversing a downward trend since 2008.

2013 data from England are not yet available, but the 14 per cent increase seen in Wales since 2012 suggests that efforts to control the infection - such as raising hygiene standards and increased use of decontamination technology like hydrogen peroxide mist - are not wholly effective.

C. difficile - known as 'C. diff' among health service staff - was recorded as the underlying cause of death in 91 cases, an 11 per cent increase on 2012, though down from the peak of 461 deaths in Wales in 2008.

Against that backdrop, the shortlisting of Astellas Pharma's C. diff treatment Dificlir (fidaxomicin) for the UK Prix Galien Innovative Product Award, reflects the critical need for additional lines of antibiotic therapy for patients who succumb to the infection.

"In combating C. difficile, Dificlir addresses a long-standing and high-profile challenge in the NHS," according to Dr Phil Wakefield of WG Consulting, which has managed the UK Prix Galien awards since 1996.

C. diff typically develops in patients where the inappropriate use of broad-spectrum antibiotics has suppressed the normal intestinal microflora, and the first line of treatment is typically to withdraw the antibiotic therapy.

In mild cases the bacterium causes diarrhoea, high fever and painful abdominal cramps but in more severe infections it can lead to life-threatening complications such as 'toxic megacolon', a severe swelling of the bowel from a build-up of gas.

Extreme cases require long-term hospital stays and treatment with antibiotics such as metronidazole and vancomycin, which is typically reserved as a last-line therapy for resistant infections.

The approval of Dificlir in Europe in 2011 came on the back of two phase III clinical studies which compared the efficacy and safety of Astellas' drug - originally developed by US company Optimer Pharmaceuticals - with vancomycin over 10 days.

"Dificlir achieved the same rate of clinical cure as vancomycin, but was significantly more effective in reducing recurrence of C. diff"

Dificlir achieved the same rate of clinical cure as vancomycin, but was significantly more effective in reducing recurrence of C. diff and had less of a destructive impact on normal intestinal flora as well as the general health of patients.

That is particularly significant as the high rate of recurrence is one of the greatest limitations of current C. diff therapies, according to Mark Wilcox, professor of medical microbiology at Leeds Teaching Hospitals.

A study conducted at St George's Hospital in London and presented earlier this year revealed that patients treated first-line with Dificlir had only a 6 per cent recurrence rate within 28 days of treatment, compared to 20 per cent with vancomycin and metronidazole.

The data from the 'real world' study also estimated a saving of more than £48,000 versus treatment compared to standard NHS therapy.

"C. diff is an increasing problem across the continent, with the incidence of infections almost doubling from 4.1 to 7.9 cases per 10,000 patient bed days"

Meanwhile, the Astellas-sponsored EUCLID prevalence study - looking at data from more than 480 European hospitals - reveals that C. diff is an increasing problem across the continent, with the incidence of infections almost doubling from 4.1 to 7.9 cases per 10,000 patient bed days between 2008 and 2013.

One of the main reasons for that seems to be a lack of clarity about guidelines which call for screening of stool samples for C. diff in cases of diarrhoea in which the cause is not clear, according to Wilcox, whose team is coordinating the EUCLID study.

"We are still seeing an issue with both a lack of clinical suspicion and lack of testing for [the infection]," he said. At the same time, the clinical consequences of C. diff seem to have worsened with evidence pointing to patients becoming generally sicker and with a higher risk of dying from the infection.

"The significant reduction in disease recurrence by Dificlir compared with vancomycin is a key step to reducing the morbidity associated with C. diff," he concluded.

The 2014 UK Prix Galien will take place on 1st October at the House of Commons, London. The Rt. Hon. Sir Kevin Barron, MP, former shadow health minister and chair of several all-party parliamentary groups relating to the pharmaceutical industry and health, will be the Parliamentary Sponsor.

Further information on the UK Prix Galien is available here.

Image courtesy of Shutterstock/anyaivanova