Bio Screening Industry News

NEW YORK, September 27, 2005- In 2004 around 366,000 patients infected with chronic hepatitis C (CHC) responded to pegylated interferon + ribavirin therapy, with 110,000 estimated in the key US market. However recent research by independent market analyst Datamonitor* (DTM.L) predicts that this number could increase three fold globally by 2014 due to increases in the rate of diagnosis and treatment. The most dramatic changes will occur if the new hepatitis C (HCV) protease and polymerase inhibitors reach the market in 2011.

The HCV virus was first characterized in 1989 and for the most part is transmitted by blood-to-blood contact, especially through transfusion (prior to widespread screening) and the sharing of needles among intravenous drug users (IVDUs). The WHO estimates that the average worldwide prevalence of HCV infection is around 3% or 170-200 million people, and variation between regions can be substantial. Areas of low prevalence (1-2.4%) tend to be within richer economies including the US, Japan, most European countries and Scandinavia whereas areas with high HCV prevalence (10%+) are located in Asia and Africa. Egypt is a notable case having a prevalence of 12%, translating into approximately 7.2 million infected individuals.

A hidden ticking time bomb

HCV remains a serious threat to present and future public health. In the US, HCV is the most common blood-bourne viral infection with an estimated 3.9 million individuals infected, 70% of which have chronic infection (1). HCV infection is assymptomatic for 90% of its history, a characteristic that not only hampers epidemiological survey of the disease, but also suggests a large number of individuals are unaware of their infection and are not receiving treatment, says Datamonitor infectious diseases lead analyst Dr John Savopoulos. “Currently 40% of chronic liver disease and 80% of hepatocellular carcinoma (HCC) is estimated to be HCV related, with the virus being the most common cause of liver transplantation in the US.”

Because the peak of HCV infection occurred during the 1970s-80s, the rate of patients presenting with HCV associated complications is expected to increase dramatically over the next 10? years. In fact, the US Centers for Disease Control (CDC) projects a four-fold increase in the number of those infected for 20 years with CHC from 750,000 to 3 million individuals from 1990-2015. Studies also suggest liver related mortality due to HCV will increase 180% in this timeframe, with HCV related direct medical costs estimated to reach $10.7billion by 2019. Clearly, better therapies for HCV eradication or those that can regress or stabilize liver disease are desperately needed.

Pharmaceutical companies Roche and Schering-Plough manufacture the latest generation of HCV treatments or pegylated-interferons known as Pegasys (peg-interferon 2a) and PEG-Intron (peg-interferon 2b). When used in combination with the broad-spectrum antiviral ribavirin (RBV), these molecules can eradicate the HCV virus in around 50% of cases. Eradication is defined as a sustained virological response (SVR) where HCV remains undetectable in a patient’s blood 24-weeks after cessation of treatment, Dr Savopoulos says. “Although not exclusively used for HCV treatment, pegylated interferons (and ribavirin) form the bulk of an estimated $2b global market for HCV treatments predicted to grow to around $4b in 2013. Datamonitor research suggests that in the US 70 – 200,000 patients per year receive pegylated interferons for HCV-therapy (compliant with the full course).”

A blunt edged tool, a growing “non responder” pool

The success of HCV combination therapy is highly genotype dependent. SVR is achieved in up to 88% of patients with genotypes 2 and 3 and but only around 48% of those infected with the less responsive ‘difficult-to-treat’ genotypes 1, 4, 5 and 6. Importantly, up to 75% of Americans are infected with genotype 1 which is thought to be more aggressive with regard to disease progression, associated with more severe liver disease and a higher risk for hepatocellular carcinoma. Patients not achieving SVR are known as ‘non responders’ and have few recommended options, Dr Savopoulos says. “Datamonitor estimates there are around 35- 100,000 non-responders to therapy per year in the US, which are predicted to number 1.4m by 2014. Without further intervention this pool will exceed the number of new diagnoses by 2013.”

New treatments in the long term?

The limitations of current HCV therapy and the growing non-responder pool provide the necessary stimulus for new product development. Datamonitor estimates there are currently around 22 compounds within clinical development falling into four main classes: the immunomodulators, interferons, small molecule antivirals and host enzyme inhibitors. More importantly, over the last year major manufacturers have openly put money on the table to join the race in finding better treatments. Novartis has established strong relationships with Idenix (NM283, valopicitabine) and Anadsys (Isatoribine, other immune enhancers); Pfizer acquired Idun for the caspase inhibitor IDUN-6556; Roche spent around $150m investing in Pharmasett’s HCV compounds (PS-6130); Schering-Plough moved closer to Migenix’s Celgosivir (MX-3253) and Gilead have recently entered the fray with GS-9132.

Because most new experimental compounds are at an early stage of development, it is still unclear how they might be used in light of the current standard of care. However Datamonitor’s research with leading HCV experts consistently found that new agents will raise current levels of awareness, thus impacting on the current rate of diagnosis and treatment. In some cases with difficult-to-treat patients, specialists might even be delaying current therapy:

“Because as we have new drugs, we will have more opportunities and of course, that’s what many patients are waiting for.” – EU Opinion Leader

“If they, again, have mild disease and very low elevations of LFTs and a bad genotype people are deferring therapy, because I think there’s a realization that probably by 2008, 2009 there’s going to be some new compounds which do much better.” – US Opinion Leader

In the US, only 20-25% of all HCV infections are actually diagnosed – a key obstacle to limiting the impact of the disease, Dr Savopoulos says. “Therefore a key message is that this predicted era of new treatments will in effect bring more patients into the treated pool, allowing more to respond to therapy regardless of whether treatment is significantly enhanced or not.”

New uses of pegylated interferons in medium term?

As well as longer term new product launches, there is the possibility that some selected ongoing trials may bring further options that benefit difficult-to-treat HCV patients. Trials such as the HALT-c and COPILOT are investigating the possibility that keeping patients on prolonged interferon or maintenance therapy may reduce progression of liver disease. Other trials, such as the Roche sponsored REPEAT trial will investigate whether patients that fail to respond to PEG-Intron after 12 weeks will respond if treated with Pegasys. Datamonitor’s HCV epidemiology model has assessed the possible impact of these events on various disease parameters taking into account comments from HCV experts:

“If this is independent, so interferon alpha acts independently of the viral load, then it [maintenance interferon] may be an option for patients in the next upcoming 5-10 years and this time, we will perhaps need them, the interferon maintenance therapy because we do not already have five drugs to make a combination therapy with antiviral drugs to inhibit the viral replication on a long term basis.” – EU Opinion Leader

“also I think you have to say would the patient put up with that [maintenance interferon]. And I think you have to look much more, not just to the benefits, but the problems of toxicity. In the UK, cost of long term interferon is costly, it’s a costly drug, and we wouldn’t actually be able to pay for it.” – EU Opinion Leader

The main results from pegylated interferon maintenance and retreatment trials are due in 2007. If positive they should drive further uptake of PEG-Intron and Pegasys which most believe have peaked for HCV use in the key US market after a decline in 2004, Dr Savopoulos says. “Nevertheless Roche, after gaining further indications in HCV/HIV coinfection and chronic hepatitis B (EU and USA), has reported that over the first half of 2005 they maintained their market leadership in pegylated interferon with sales growth of 15%.”

“This current data supports Datamonitor’s long term outlook – that unless a generic pegylated interferon reaches the market and/or a cocktail of safe HCV antivirals proves more effective, the current standard of care is here to stay for a good many years,” he says.

Ends

Notes for editors * Hepatitis C epidemiology model

(1)NHANES III Datamonitor’s Hepatitis C epidemiology model features patient flow analysis of the HCV population over 10 year forecast period. The model includes segmentation by line of therapy along with quantification of responder, non repsonder and re treatment pools.

Dr John Savopoulos, Datamonitor infectious diseases lead analyst is available for comment

To arrange an interview or for further details regarding the report contact Matthew Dick in the Datamonitor Press Office on + 44 20 7675 7824, or email mdick@datamonitor.com

For US, please call Suzanna Eygabroat on +1 585-374-6326 x17 For Asia-Pacific, please call Denis Mason on +61 2 9006 1526.

Datamonitor plc (DTM.L) is a premium business information company specialising in industry analysis. We help our clients, 5000 of the world’s leading companies, to address complex strategic issues. Through our proprietary databases and wealth of expertise, we provide clients with unbiased expert analysis and in-depth forecasts for six industry sectors: Automotive, Consumer Markets, Energy, Financial Services, Healthcare, Technology. Datamonitor maintains its headquarters in London and has regional offices in New York, San Francisco, Sydney, Tokyo, Frankfurt, Shanghai and Hong Kong. See www.datamonitor.com for further details.