NATAP: 22 New HCV Drugs in Development

[Guest guest]

NATAP - http://www.natap.org

22 New HCV Drugs in Early Development

One million hepatitis C patients could respond to therapy by 2014

4-fold increase expected by 2015 in those with chronic HCV for 20 years; liver related mortality to increase by 180%; HCV related direct medical costs estimated to reach $10.7billion by 2019; in US, 20-25% are diagnosed. 22 new compounds for HCV therapy in early development

30 Sep 2005, 13:06 GMT - In 2004 around 366,000 patients infected with chronic hepatitis C responded to pegylated interferon + ribavirin therapy. However, new research 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 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-borne viral infection with an estimated 3.9 million individuals infected, 70% of which have chronic infection. HCV infection is asymptomatic 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 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.â€

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 10-20 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 chronic hepatitis C (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).â€

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:

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.â€

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.

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%.â€

“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."

Source: Datamonitor Expert View