The aim of this post is to give you all an update on the Hepatitis C drugs coming to license soon – however its so friggin’ complicated it’s making my head hurt. But here we go…
A quick look at a diagram listing all drugs in the pipeline shows you why:
There are quite a few in phase 2,3 and 4 studies.
So, if its helpful I’m going try and give you a quick run-down on Hepatitis C and talk about just a few of the treatments coming soon.
Hepatitis C is a disease of the liver caused by the Hepatitis C virus (HCV) Although its transmission routes go hand in had with HIV its mode of action and treatment is far from similar. Firstly HCV can be fully cleared from the body with successful treatment- the emphasis is on the word successful.
Without treatment the inflammation caused by HCV leads your liver to progress from fibrotic to cirrhotic and increases your risk of liver cancer – as shown below. With just HCV this may take a few decades, add HIV or alcohol to the mix and this progression speeds up considerably.
Historically the treatments with Pegylated Interferon (Peg) and Ribivirin (Rbv) have taken from six months to a year and cause side effects like anaemia and depression. These treatments have given us cure rates of around 30-40% and that’s if your liver isn’t too damaged to undergo treatment. Giving someone who is cirrhotic Interferon can sometimes push a knackered liver over the edge with not such a great outcome.
In 2012 two new drugs came on license, Telapravir and Bocepravir – both when added to Peg/Rbv increase cure rates to 70%. But these need to be taken two or three times daily and bring with them new side effects. The goal is to find treatments that can be used without interferon (the main cause of the side effects) and that’s what’s coming.
- Treatments that dont need to be taken every 8 hours with 20g of fat
- Treatments that have fewer side effect
- Treatments that are simple to take
- Treatment that have over 80% cure rate
Direct Acting Antivirals (DAAs), which attack specific parts of the HCV lifecycle in a similar way that HIV drugs work, have been all the rage in the world of clinical trials over the last couple of years. With DAA we’re talking cure rates of over 80% with three to six month courses without interferon.
The reason why its not 100% effective for everyone is because it depends on both genotype and liver progression. The more fibrotic your liver is the harder it is to treat. One thing we have learned in the waiting game is DO NOT let your liver get cirrhotic.
With 6 different genotypes, each genotype reacting differently to different drugs, it becomes even more complicated. We know from trials that some of the new drugs are brilliant against genotypes 1,2 & 4 but not as effective against genotype 3.
Also where they have identified different drug classes, trials continue to find which drugs from which class can be used successfully together to form dual or triple therapy where needed. The first of these new drugs will be licensed this year, with Gilead Sciences’ SOFOSBUVIR showing promising results without interferon in genotype 1 patients with no cirrhosis.
Second generation PI’s like Jansen’s SIMEPRAVIR and Boehringer Ingelheim’s FALDAPREVIR are also coming soon with great results with interferon and ribivirn and promising trial results when added to other new agents. Bristol Myers Squibb’s drug DACLATASVIR paired with Gilead’s SOFOSBUVIR cured 100% of genotype 1 patients in a small trial of 41 people who previously failed treatment, however Gilead are concentrating on using a single pill combo of SOFOSBUVIR with their own drug LEDIPASVIR to gain maximum profit rather than work with the Bristol Myers Squibb drug and again this is showing fantastic results.
Here are some interesting links on licencing and trial data if you’re interested:
This is just a few, a small selection of the treatments in the pipeline, there are way too many drugs and trials to list here.
Ultimately all this pharma company wrangling and ongoing trials mean nothing to the person waiting at home with liver disease for these new drugs to arrive. When they do arrive there is going to be a further battle to get your NHS Trusts to pay for it as they are going to be incredibly expensive (rumours of up to £100,000 per course of treatment for some drugs) so currently its all about making sure you have a good doctor who is monitoring your liver properly while you wait.
If your liver start to progress to more fibrotic or cirrhotic then have a serious chat about using the treatments available now and seriously consider joining a clinical trial. These are pre-licencing trials run via NHS clinics to gather large amounts of data. You will be looked after exceptionally well. Getting onto a clinical trial not only offers you a higher chance to cure your Hep C but also helps the millions of people worldwide who are waiting in the queue.
Andrew Crawford-Jones (@acj_uk on twitter)