Hepatitis C has been described by the World Health Organisation as a “viral time bomb,” and the disease is thought to affect around 1%-2% of Europeans and around 30 million-40 million people in the first world alone.
But this is just an estimate, as many carriers remain undiagnosed because the disease has no symptoms until it matures, and the majority only discover they are infected with the virus by mistake. This problem is magnified by the fact that HCV spreads very easily – just using the same toothbrush as a person carrying the virus can lead to infection.
Furthermore, the disease seems to have little effect on a patient for the first 30 years or so after they become infected. But HCV has a non-linear progression, Professor Graham Foster, Barts and the London, Queen Mary’s School of Medicines and Dentistry, explained to attendees at a meeting organised by UK group Phynova in London last week. After 30 years or so, things start to get very serious very quickly, and there is a dramatic increase in the development of liver cirrhosis, which can lead to liver cancer or liver failure.
Liver transplants are needed in 5%-10% of patients with cirrhosis every year, he said, and pointed to a study by Ryder et al which put the cost of this per patient per year at £29,938. This “cost will dominate healthcare thinking over the next 15 years,” Prof Foster warned. Add to this the expense of treating patients in other stages of the disease, and you get a hefty strain on the National Health Service’s already stretched finances.
Standard treatment for chronic HCV involves injections of pegylated interferon and oral doses of ribavirin. Response rates are around 40%-50% in patients with the harder-to-treat genotype 1, and just 70%-90% in those with genotype 2. And the severity of the therapy’s side effects means that around 20%-25% of patients stop treatment, according to Dr John Efthimiou, Chief Medical Officer of Phynova. As Prof Foster described, interferon causes tiredness, fever and depression, while Ribavirin can give patients anaemia, skin rashes, a funny taste in the mouth and a dry cough. So persuading patients to remain on therapy is a big challenge, and a lot aren’t cured because they don’t complete treatment, he said.
According to Prof Foster, his holy grail would be a “safe medicine that improves response rates and reduces the side-effects of therapy,” although he concedes that this is probably a long way off, and voiced concerns that many of the new drugs in trials are adding to the side-effect burden rather than reducing it.
There are several therapies being tested for HCV by companies working hard to meet this unmet medical need and get a slice of a market which, according to Arrow Therapeutics’ Commercial Director Dr Barbara Domayne-Hayman, will likely grow from $3 billion in 2007 to $8 billion in 2015.
Different R&D approaches include: protease inhibitors, the most advanced of which is Vertex’ VX950, currently in Phase II; polymerase inhibitors, which were led by Idenix/Novartis’ valopicitabine until it was announced this week that its development is being terminated as the overall risk/benefit profile was not favourable; immuno-modulators such as Anadys/Novartis’ ANA975 in Phase 1b; targeting NS5a, which is being investigated by Arrow Therapeutics in Phase I trials; and others, such as Phynova’s plant-based agent PYN17.
At a meeting in London last week, Dr Efthimiou showcased the potential of PYN17 as an effective treatment for HCV. The product is comprised of four widely-prescribed medicinal plants with a long history of human use, and safety and efficacy in liver disease. But according to Dr Efthimiou, what really sets PYN17 apart from other candidates is that it is the only drug in development for the treatment of symptoms as well as liver inflammation in chronic HCV.
The company says that, unlike antiviral therapy, PYN17 offers a multivalent approach: it is an anti-viral, anti-inflammatory, anti-oxidant, and anti-fibrotic. Importantly, a recently completed Phase II clinical trial demonstrated that the agent is well tolerated with no drug-related adverse events recorded, and it had a clinically significant benefit on patients’ quality of life as well as showing a strong trend for reducing levels of harmful liver enzymes. PYN17 is currently in a Phase IIa trial in the USA, and a pivotal Phase IIb study is scheduled for the first quarter of next year.
Ticking time bomb
But back to the UK, and the NHS is likely facing a ticking time bomb with HCV, experts have warned. As Prof Foster points out, there are currently around 600,000 people carriers in the country, and most of these were infected in the 1970s through drug abuse. As it takes 30-40 years to develop cirrhosis, we are likely be facing an explosion of patients needing expensive therapy to try and combat the disease.
Any yet little is being done to raise the profile of HCV. There are no screening programmes for HCV in the UK. And, according to Prof Foster, although the Department of Health is currently running a campaign to raise awareness, most people aren’t even aware of the awareness campaign. Perhaps, he suggests, this has something to do with the fact that just £250,000 over five years has been allocated to the campaign, which is relatively little compared with the £4 million a year the government spends on advertising the change to digital TV.