UK Prix Galien: New treatment for multidrug-resistant TB
This article is the latest 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 1 October, we look at Janssen’s Sirturo, the first drug with a new mechanism of action against tuberculosis in 40 years.
Twenty years ago, tuberculosis (TB) was largely considered a disease which medical science and the pharmaceutical industry had under control.
While the BCG vaccine, introduced in 1921, provided only limited protection against the infection, antibiotic therapy was generally effective provided, of course, you could gain access to it. The prognosis for treated patients was bright, on the whole.
In the last couple of decades the picture has darkened significantly. The number of patients presenting with TB that is resistant to at least two of the most powerful medicines in the standard four-drug therapy is on the rise, killing 150,000 people a year.
“Multidrug-resistant TB will infect more than two million people between 2011 and 2015”
So-called multidrug-resistant TB (MDR-TB) will infect more than two million people between 2011 and 2015, according to figures from the World Health Organization (WHO), which issued a Call to Action five years ago to address the ‘alarming threat’ of MDR-TB and warned last year of a $1.3 billion funding gap for TB research.
In March 2013 Dr Margaret Chan, director general of the WHO, warned: “We are treading water at a time when we desperately need to scale up our response to MDR-TB.”
Mycobacterium tuberculosis – the bacteria which causes TB – generally attacks the lungs but can also infect the kidneys and brain and, without effective antibiotic therapy, can be life-threatening.
Around one out of 100 patients who contract TB develop a latent infection, in other words carry the bacteria but exhibit no symptoms. While they are typically non-infectious while latent, eventually breakthrough, active infections occur in up to 10 per cent of patients.
“There is a critical unmet need for new MDR-TB treatment options,” according to Andrew Murungi, scientific advisor for infectious diseases in the medical affairs unit of Johnson & Johnson’s UK subsidiary Janssen, whose new TB drug Sirturo (bedaquiline) has been shortlisted for this year’s Prix Galien awards in the innovation category.
“Bedaquiline was given a conditional approval in Europe … becoming the first therapy with a novel mechanism against TB in more than 40 years”
Bedaquiline was given a conditional approval in Europe earlier this year on the strength of phase II trials, becoming the first therapy with a novel mechanism against TB in more than 40 years. It works by inhibiting mycobacterial ATP (adenosine 5’triphosphate) synthase, an enzyme essential for the generation of energy in the bacteria.
“Current treatment is lengthy, complex and toxic and typically consists of a two-year regimen with up to six second-line drugs,” he told pharmaphorum.
Adding bedaquiline to the current MDR-TB regimen has been shown to improve clinical cure rates compared to placebo, with Janssen’s drug achieving negative sputum cultures in around 58 per cent of patients, compared to 32 per cent with placebo.
Moreover, the drug has also been shown to be cost effective, increasing the proportion of patients who achieve a negative sputum culture, which translates into savings on hospital costs, according to Murungi.
“Bedaquiline is associated with fewer transmitted cases, fewer cases of acquisition of resistance and a higher success rate than other treatments,” he added.
The need for effective antibiotic therapy for TB has become even more pressing with the failure of medical researchers to develop an effective vaccine against the bacterium.
Last year, for example, a team led by scientists at the University of Oxford suffered a major setback after a vaccine candidate called MVA85A that had been in development for more than a decade, failed to protect babies who had already received the BCG shot.
“Effective treatment of patients with MDR-TB with bedaquiline will have important public health benefits by reducing the spread of MDR-TB and preventing the progression to more resistant forms,” said Murungi.
Further information on the UK Prix Galien is available here.