New treatments mean ‘higher success rates’

September 7, 2012 By Pat Kelly

New medications for hepatitis C have been judged cost-effective by the National Centre for Pharmacoeconomics and State reimbursement has been given to the treatments, hailed as a significant breakthrough, reports Gary Culliton.

Chronic hepatitis C poses a public health burden and up to 50,000 Irish people currently have the virus. It is an infectious disease but patients are often asymptomatic for long periods. If it remains untreated, it can lead to severe liver conditions. About 25 per cent of people infected can progress to cirrhosis, which in turn can lead to liver transplantation and liver cancer.

The standard treatment for hepatitis C (peginterferon alfa and ribavirin) is successful in only about 50 per cent of patients with genotype 1, leaving the other 50 per cent without a successful treatment outcome.

For 15 years, hepatitis C treatment barely changed. Last month’s reimbursement approval for new therapy radically changed the treatment environment and heralds a new generation of drugs to treat hepatitis C, according to a leading Dublin hepatologist. “This is a paradigm shift for treatment of the most common type of hepatitis C, genotype 1,” said Dr Raphael Merriman, Consultant Hepatologist at St Vincent’s University Hospital, Dublin. “It is the most important approval of new agents since 1998.

The addition of a protease inhibitor nearly doubles the chances of cure for patients who have never been treated previously and also substantially improves response rates for those who have undergone unsuccessful treatment in the past. Two protease inhibitors — boceprevir and telaprevir — will now be available for Irish patients.”

Drug pipeline

The latest direct-acting antivirals (DAAs) are the first of a whole host of new drugs that will be coming on-stream in the next three-five years. There are between 20 and 30 such drugs in various phases of clinical trials, which will further increase the efficacy of treatment for hepatitis C — hopefully with shorter treatment durations. Some studies even involve the absence of interferon, which is much disliked by patients due to its side-effects.

The protease inhibitors effectively double the ‘cure rate’ among treatment naïve patients: getting rid of the virus, six months after the end of treatment. These are people who have not previously been treated with interferon. The chance of a cure in this group rises dramatically from 40 per cent to between 70 and 75 per cent.

There is greater complexity of care: patients need to be seen and monitored more frequently. However, about two-thirds who are treatment naïve will qualify for shortened treatment. The response rates for people who are treatment experienced are less but still much better than they were, when just interferon and ribavirin were available.

Where there have been prior attempts at treatment, most of those people will require the full 48 weeks of treatment (including a protease inhibitor).

Dr Orla Crosbie, Consultant Hepatologist and Gastroenterologist from CUH, said: “The availability of direct-acting antivirals in Ireland means success rates for treatment will now be significantly higher. In addition, treatment duration will be far shorter for many groups of patients.”

Older drugs were more ‘blunderbuss’ in their effects, Dr Merriman added. A combination of two medications in pill form is currently required, along with the continued use of a subcutaneous injection, and the current standard of treatment is 48 weeks. The new three-drug combination treatment is more efficacious and treatment can now be shortened from 48 weeks to between 24 and 28 weeks, in a majority of those who have not been treated before, he said.

Interferon and ribavirin were much blunter instruments, Dr Merriman explained. The newer agents, such as telaprevir, are much more focused and specific in the target sites where they act, he added.

Thought will be required on the part of hepatologists as to which patients are best suited to which of the new drugs. The consensus is that people with more advanced disease — typically defined as more significant fibrosis or scarring in the liver — should be first in line for treatment.

Protease inhibitors such as boceprevir and telaprevir help stop genotype 1 infection — the strain affecting over 50 per cent of the Irish hepatitis C population. Genotype 1 is the infection least amenable to currently available therapy. Treatment will be rolled out in tandem with the national hepatitis c Register, to analyse data and determine outcomes. Treatment will take place in a limited number of centres (five in Dublin and also at University College Hospital Galway, St Luke’s in Kilkenny and Cork University Hospital) where there is expertise in treating the condition. The new drugs are not aimed at people with hepatitis genotypes 2 and 3.

Once the virus is gone, treatment continues. After 24 weeks following the end of treatment, tests are conducted for the presence of the virus. The relapse rate is very low, said Dr Merriman. If the virus is still gone at this point (Sustained Virological Response, SVR), this effectively translates to a cure. Both in people who have never been treated and those who have been treated before, the SVR rates are nearly double what could be achieved with previous therapy.

The National Centre for Pharmacoeconomics has judged the new protease inhibitors to be cost-effective. Five sentinel studies published in the New England Journal of Medicine (NEJM) last year provided compelling data that these drugs work, explained Dr Merriman. Authorisation for telaprevir is based on results from three phase III clinical trials, ADVANCE, REALIZE and ILLUMINATE. These evaluated the efficacy and safety of telaprevir in combination with peginterferon alfa and ribavirin in more than 2,290 treatment-naïve and previously-treated chronic genotype 1 hepatitis C patients. Data from ADVANCE and REALIZE were published in the June 23 edition of the NEJM. Data from the ILLUMINATE study were published in the September 15 edition.

Because there are three different drugs, the new ‘triple therapy’ (of protease inhibitors, interferon and ribavirin), works on several different mechanisms. One of the new protease inhibitors is given in combination with the previous two-drug combination. Effectively, the treatment suppresses and ultimately eradicates the virus.

Source