Cancer Drug Discoveries: Colorectal Cancer

The worldwide incidence of colorectal cancer (CRC) is approximately one million cases per year and, in the US, it is the third most common cancer in both sexes, accounting for around 8.5 per cent of all cancer deaths.

The rise of targeted therapies
In 2008, the CRC drug market (US, EU and Japan) for major branded therapies was valued at just over US$8 billion. Whilst chemotherapy is the mainstay of CRC treatment, driven by sanofi-aventis' Eloxatin (oxaliplatin), Pfizer's Camptosar (irinotecan) and Roche's Xeloda (capecitabine), the use of targeted therapies such as Roche's Avastin (bevacizumab), Eli Lilly/Bristol-Myers Squibb/Merck KGaA's Erbitux (cetuximab) and Amgen's Vectibix (panitumumab) are gaining acceptance in the treatment of advanced disease. We expect this trend to continue as new combinations are evaluated and therapies are increasingly used in the adjuvant setting to address the unmet clinical needs within the market. However, a number of leading CRC agents already face, or will face, generic competition over the next few years, which will radically change the dynamics of the market and potentially increase price sensitivity.

Intense research is producing new approaches
There were 64 drugs being evaluated for the treatment of CRC in 2008, out of a total 750 products in clinical development for the treatment of cancer. Several companies now have potential CRC drugs in late-stage clinical development. The majority of projects are in Phase II trials, with several new treatments becoming available in the near term for both early and advanced CRC.
By 2015, targeted therapies will account for 77% of the colorectal market. Which products and companies will benefit from this trend and who may lose out?

Early-stage CRC is generally treated with surgery and radiation, with a high percentage of patients going on to survive disease-free. Since the disease is usually asymptomatic at this early stage, screening is necessary to provide patients with the best chance of a potential cure.

Unfortunately, only around 40% of CRCs are found at this early stage, and, as a result, there remains considerable unmet clinical need within the CRC market. For those patients who experience recurrence following surgery, there is a clear need for effective therapies earlier in the course of the disease. In addition, with around 76% of patients (Stages II-IV) eligible for chemotherapy, new formulations that improve patients' quality of life and increase survival are sorely needed.

The advent of personalised medicine?
To improve patient care and reduce expenditure on ineffective treatments, much hope is resting on the potential for tailored treatment regimens to fit patients, ie, the advent of the era of personalised medicine. For example, both Erbitux and Vectibix have been shown not to work in CRC patients who have a mutation in the KRAS gene (approximately 40% of patients), resulting in their approval only for those patients lacking the mutation.

Shape of the industry - 2015
By 2012, we expect products with alternative approaches to the inhibition of the VEGF pathway to begin challenging Avastin's dominance. AstraZeneca will enter the CRC market for the first time with Recentin, which could prove to be a major competitor given that it requires once-daily oral administration and has a relatively benign safety profile. In addition, sanofi-aventis' aflibercept (VEGF Trap) may increase options for patients with metastatic CRC. By 2015, we predict that Roche will continue to dominate the market, increasing its market share to 54% as Avastin continues to assert itself as a front-line therapy in both early and advanced CRC.

Two novel therapies may reach the market for the first time by 2015:

Vaccinogen has opted for a high-risk/high-reward strategy by developing what may prove to be the first vaccine for CRC. OncoVAX may become available from 2014 onwards for Stage II colon cancer patients, where currently the only approved treatment is surgery.

Light Sciences Oncology's Litx Therapy has potential as the first photodynamic therapy for CRC. With the absence of a cure for advanced disease, a therapy that can offer some potential without the debilitating side effects of current chemotherapy is sorely needed.

Growth driver: adjuvant prescribing increases growth
Treatment for early-stage CRC has historically included only surgical resection, however 5-year overall survival rates decrease from 90 to 67% if the cancer spreads to nearby lymph nodes and organs. Recent trials suggest that the use of chemotherapy following surgery (adjuvant) can lead to significant improvements in survival in early CRC.


About the Author
This report has been researched and written by senior Espicom pharmaceutical analyst, Sue Viney. For over 10 years she has played a pivotal role in tracking trends in drug development and corporate performance. In addition to this report she has produced detailed product analysis in the CNS, Breast/Lung Cancer and Rheumatoid Arthritis sectors.