Hepatocellular carcinoma: pointing the way for other niche cancers 

Hepatocellular carcinoma is the fourth most common form of cancer worldwide, and yet there is still no effective therapy available. Currently only 5% of patients in the developed world survive five years but new products are likely to reduce mortality rates. This market could set a precedent for other underserved niche cancers, attracting attention from drug makers keen to capitalize on the unmet patient potential.

Hepatocellular carcinoma (HCC) is a tumor of the liver that arises from focal scarring points in cirrhotic liver tissue. Cirrhosis resulting in HCC is commonly linked to chronic hepatitis B and C infection, alcoholism and in developing countries, exposure to aflatoxin, a toxin found in moldy grain.

The high level of hepatitis infection in the US and a number of the European markets is expected to greatly increase the incidence of HCC in the next five years, with many specialists describing the problem as a "waiting epidemic".

However, HCC is a far greater problem in Southeast Asia and Sub-Saharan Africa, where low water quality and exposure to aflatoxin, combined with the high levels of chronic hepatitis infection have produced high levels of severe liver cirrhosis. This has resulted in countries such as China and South Africa suffering incidence rates of HCC 10 times those found in the West.

Ineffective treatments

Because HCC is most common in patients with already impaired liver function, surgery or transplant is only possible in a small number of cases. This leaves over 90% of patients requiring other interventions, such as radiotherapy and chemotherapy.

But radiotherapy is associated with strong hepatotoxicity, removing another therapeutic option and chemotherapy is largely ineffective, with the most commonly used drug, doxorubicin, having strong activity in only 15-20% of patients. This has led to desperate physicians using many novel techniques to try to halt the progress of the disease, most of which are only effective in producing a short-term remission.

Prevention is possible

Vaccines for hepatitis B are now available, and their introduction in many of the more affluent developing countries such as Thailand and amongst the at-risk populations in Europe and the US is likely to significantly reduce incidence of HCC.

However, these immunization programs are not expected to achieve their effect until at least 2015. These programs are likely to be especially effective in developing countries where childhood hepatitis infection can lead to HCC and death by as young as fifteen years of age.

"Amazingly, although HCC is the fourth most common tumor in the world, the disease is uncommon in individuals without liver cirrhosis," Andrew Hingle, oncology analyst at Datamonitor, comments. "Immunization programs for hepatitis B represents only a small proportion of what can be done to reduce the incidence of HCC."

"Vaccines for hepatitis C may become available by the end of the decade, food storage and water sanitation are constantly improving and the dangers of alcoholism are receiving more attention than ever before."

Here comes the cavalry...

A number of new agents are in development for hepatocellular carcinoma, and although none represent a cure, many are more effective than the currently available drugs. Consequently, if a patient's chronic liver disease can be managed, these drugs may represent a significant improvement in the life expectancy of HCC patients.

The impending launch of a number of products that address the high levels of unmet need in HCC will cause the rapid expansion of the market, as physicians desperate for any improvement in the clinical management of HCC rapidly switch from current gold standard drug regimens or second line interventions to newly available patented drugs with correspondingly high price points.

Datamonitor predicts this growth to start with the launch of Eximias' Thymitaq in 2005 and continue with the release of Tularik's T67 in 2006, leading to growth from a market value of $70.1 million in 2002, to $286 million in 2010.

Niche and easy

The high level of unmet need commonly associated with niche tumor indications has made them an attractive area for investment. The current dearth of effective pharmacological treatment for many niche tumors means that drugs offering relatively modest improvements in response rates or, more importantly, overall survival, will gain strong uptake.

Certainly this has been the case for Eli Lilly's Gemzar (gemcitabine) in pancreatic cancer. Gemzar's presence as the gold-standard therapy for advanced pancreatic tumors was established almost exclusively on the basis of its ability to improve quality of life, rather than any significant benefit in terms of survival.

Yet since its launch in pancreatic cancer in 1996, Gemzar's sales in this indication have grown from $64 million to around $390 million in 2002. Due to its success, Gemzar has become the model for achieving sales in niche tumor indications, a strategy that can only benefit both patients and manufacturers.

"For those drugs in development for niche tumors that offer a significant improvement to the existing standard of care, there is the potential to capitalize on the intense demand within this indication, positioning the drug at a high price-point," says Mr Hingle.

This situation is currently epitomized in the HCC market, where agents approved for the tumor could potentially gain strong sales despite the relatively small number of patients currently associated with the disease in Western markets.

As with other niche cancers, HCC offers the benefit of both an accelerated and, arguably, easier route to the marketplace compared with that for many of the larger tumor types.

"Drugs in development for HCC may be able to gain approval on the basis of phase II trials in the US, reducing the costs and risks associated with development," Mr Hingle continues. "Once launched, revenue from the HCC indication could be used to fund further trials, and physician familiarity with drug use for HCC and with off-label use can result in a shorter 'lead-time' for subsequent indications."

If you found this week's Expert View useful, you may be interested in Datamonitor's reports:

• Strategic Perspectives: Hepatocellular Carcinoma: T67 and Thymitaq to Create Market Value

• Strategic Perspectives: Hepatitis B and C - Strategic Developments in an Immature Market

• Healthcare Review: Cancer - November 2002

To order these reports - click here! - then search by title or contact sales@bioportfolio.com