September 24, 2008

ImClone/BMS/Merck Serono

Bristol-Myers Squibb and ImClone have presented five year data demonstrating an improved survival rate for head and neck cancer patients when receiving Erbitux and radiotherapy. Erbitux was the first targeted therapy to reach the market for this indication and looks set to maintain its market share on the basis of this positive data.

The Phase III IMCL-9815 trial enrolled 424 previously untreated patients with locally or regionally advanced squamous cell carcinoma of the oropharynx, larynx or hypopharynx. Patients were randomized to receive Erbitux with radiotherapy (211 patients) versus radiotherapy alone (213 patients). Analysis of data at a five year follow-up was reported. Median overall survival was 49.0 months in Erbitux-treated patients and the five-year survival rate was 45%. This is in comparison with median overall survival of 29.3 months and a five-year survival rate of 36% for those treated with radiotherapy alone.

Erbitux is a recombinant human/mouse chimeric IgG1 monoclonal antibody. It binds to the epidermal growth factor receptor (EGFR) and prevents tyrosine kinase autophosphorylation, which blocks intracellular signal transduction and interferes with a variety of downstream signals critical to tumorogenesis and angiogenesis.

Erbitux was approved in the US and EU in 2006 for the treatment of locally or regionally advanced squamous cell carcinoma of the head and neck in combination with radiotherapy, and as a single agent for recurrent or metastatic head and neck cancer following the failure of prior platinum-based therapy. These approvals were based on three-year survival data from the Phase III IMCL-9815 trial.

Although Erbitux is currently the only approved targeted therapy for head and neck cancer, there are a number of drugs in late-phase clinical trials, including several that also inhibit EGFR: Tykerb (lapatinib; GlaxoSmithKline), Vectibix (panitumumab; Amgen) and zalutumumab (HuMax-EGFR; Genmab).

Vectibix is likely to provide the strongest competition to Erbitux. It is a fully human monoclonal antibody which should in theory result in fewer side effects than Erbitux's chimeric formulation. Like Erbitux, Vectibix is also approved for colorectal cancer, but Amgen's drug is cheaper than Erbitux in this indication. However, it will be sometime before Vectibix reaches the market for head and neck cancer, ensuring that Erbitux faces no imminent threat.

The fact that Erbitux was approved for locally or regionally advanced head and neck cancer based on three-year survival data shows that the FDA and EMEA regard the drug as effective in this patient population. Positive five-year follow-up data will only serve to strengthen Erbitux's position in this specific patient population and thereby allow it to maintain its leading status in the head and neck cancer market.