UK chooses Cervarix over Gardasil

The Department of Health (DoH), UK, has awarded the contract to provide the vaccine against human papillomavirus (HPV) to GlaxoSmithKline for its product, Cervarix. The contract is to supply the vaccine that protects against cervical cancer (CC) and precancerous cell changes in the cervix caused by HPV. The vaccine will guard against the two HPV strains that cause 70 per cent of cases of CC, types 16 and 18. The vaccine will be made available to girls aged 12 to 13 years from September, while a year later it will also be administered to girls up to 18 years of age in a two-year, catch-up programme.

GSK's CC vaccine is approved in 64 countries worldwide, but this was the first major national tender for which the company had bid. According to Eddie Gray, President of Pharmaceuticals Europe for GSK: "This is great news for girls and women across the UK and reflects the growing confidence in Cervarix, which provides cervical cancer protection with a strong and sustained immune response."

The UK's Joint Committee on Vaccination and Immunisation, which provides independent expert advice to ministers on vaccination, examined a wide range of evidence before recommending in June 2007 that an HPV vaccination programme be routinely introduced for 12 to 13 year old girls. However, this left the DoH to choose between Cervarix and its competitor, sanofi pasteur MSD's (sanofi-aventis and Merck & Co joint venture) Gardasil (quadrivalent HPV types 6, 11, 16, 18, recombinant vaccine), which are both licensed in the EU.

An adjudication was carried out to examine the vaccines offered against a wide range of criteria, such as their scientific qualities and cost effectiveness. The criteria used for the adjudication had been shared in advance with the companies which tendered. Following this process, the DoH selected Cervarix, going against the decision of many EU countries who have opted for Gardasil and the wider protection it offers. Commenting on this, Dr Nicholas Kitchin, UK Medical Director, sanofi pasteur MSD, stated: "We regret that school girls in the UK, unlike most of their peers in Western Europe, the USA, Australia, New Zealand and Canada, will not benefit from the unmatched cervical cancer protection and additional benefits provided by the world's leading HPV vaccine, Gardasil."

Cervarix uses GSK's proprietary AS04 adjuvant as its main differentiating point, which may enhance the immunogenicity of the vaccine, therefore potentially reducing the need for booster shots. However, the long-term efficacy of the two vaccines is believed to be similar.

The key reason for the DoH choosing Cervarix is likely to be price. With a list price for a full course of Gardasil as high as US$375 per person in the US, HPV vaccine costs are a key issue. Although the cost of Cervarix is commercially confidential, it can presently be administered through private clinics at a cost of £130.00 per injection (the immunisation course consists of three injections). GSK may have offered a heavily discounted price, relative to Gardasil, making the DoH’s decision easier. Another factor that must not be forgotten is the fact that GSK is, after all, a British company.

Matthew Dennis - Editor, Cancer Drug News

Ten years of rituximab

As MabThera (rituximab) reaches ten years of market availability in Europe for the treatment of non-Hodgkin's lymphoma (NHL), what does the future hold for the monoclonal antibody (MAb)?

Approved in June 1998 by the EC, although launched earlier in the US (where it is known as Rituxan), rituximab (formerly IDEC-C2B8) was the first anticancer MAb, heralding an influx of the molecules into treatment regimens for multiple tumour types. Originally discovered by IDEC (now Biogen Idec) and jointly developed along with Genentech, Roche and Zenyaku Kogyo, the MAb targets the CD20 protein that is expressed on over 95 per cent of B-cell lymphomas. It was the first MAb therapy to demonstrate a clinically-significant antitumour response, which finally provided proof of principle that these molecules could be efficacious, as well as specific and less toxic. Such a combination of attributes has seen rituximab realise significant revenue, with sales of US$2,252 million in 2006 and US$2,515 million in 2007.

Rituximab was initially approved to treat only a specific subset of patients with NHL. Over the years, the MAb has gained approval to treat additional types of NHL and has become a front-line therapy when used in combination with various chemotherapy regimens. But what about the future of the MAb? Ongoing clinical studies are investigating the long-term use of rituximab as a maintenance therapy to prevent relapse in patients with follicular lymphoma. These trials have shown that maintenance therapy prolongs the duration of remission and that the MAb can be safely administered for up to two years. Additionally, rituximab is in Phase III trials for relapsed and first-line chronic lymphocytic leukaemia. Rituximab has also been approved in areas outside of oncology, such as for the treatment of rheumatoid arthritis, and is being investigated as a therapy for lupus, multiple sclerosis and platelet disorders.

Sales of rituximab look set to remain at a steady level for the next five years, however, in April 2007, Dr Reddy's Laboratories launched Reditux, its brand of rituximab, in India. Reditux, for the treatment of NHL, is priced at around half the originator’s price. Dr Reddy's also announced plans to market Reditux in other markets, including the US, when the product's patent expires in 2015.

The success of rituximab has paved the way for the development and approval of additional anticancer MAbs, treating tumour types such as colorectal, breast, lung, and head and neck cancer. Rituximab has not only altered the way that NHL is treated, but it has significantly changed the approach to cancer drug development. MAb therapies are now an essential part of cancer treatment regimens and clinical trials. Future challenges will involve how to best incorporate new MAb therapies with current treatments, including new forms of immunotherapy. Despite the threat of future biosimilar competition, there is clearly life still left in the original MAb.

Matthew Dennis - Editor, Cancer Drug News

Studies link oral disease and cancer

According to results from two recent studies, periodontal disease and tooth loss are associated with an increased risk of certain malignancies, including those involving the kidney, pancreas, oesophagus, head and neck, and lung. The reason for the associations are unclear, but could be due to the fact that periodontal disease is either a marker for a cancer-susceptible immune system or has a direct carcinogenic effect. The scientists speculate that bacterial infection and inflammation resulting from poor oral care that leads to tooth loss could also be driving development of these cancers.

In the first study, published in the 6th May online issue of The Lancet Oncology (10.1016/S1470-2045(08)70106-2), researchers from Imperial College, London and the Harvard School of Public Health analysed data from the HPFS (Health Professionals Follow-up Study), a survey of male health professionals in the US that was initiated in 1986. The subjects completed general questionnaires at baseline and then every two years, as well as dietary questionnaires every four years.

During a median follow-up period of 17.7 years, 5,720 incident cancer cases were documented among 48,375 participants. The most common malignancies were colorectal, melanoma, lung, bladder and advanced prostate. After accounting for smoking, diet and other known risk factors, a history of periodontal disease was linked to an increased risk of cancer, with a hazard ratio (HR) of 1.14. In terms of specific malignancies, the HRs were 1.36 for lung cancer (LC), 1.49 for kidney cancer, 1.54 for pancreatic cancer and 1.30 for haematologic cancers.

Among never-smokers, periodontal disease was linked to total and haematologic cancer, but not to LC. Thus, the overall link between periodontal disease and LC probably resulted from residual confounding due to smoking. According to the study authors, given the systemic effects of periodontal disease and the potential involvement of the immune system, as a marker of susceptibility or through changes in immune surveillance, further research on the role of periodontal disease in cancer, especially haematological cancers, is warranted.

In the other study, published in the May edition of Cancer Epidemiology Biomarkers & Prevention (2008;17:1222-1227), researchers from Aichi Cancer Center in Nagoya and Nagoya University School of Medicine measured rates of 14 different cancers and rates of tooth loss in 5,240 cancer patients in Japan, and compared those rates among 10,480 matched cancer-free participants. The investigators specifically found that people with tooth loss were 136 per cent more likely to develop oesophageal cancer (OC), had a 68 per cent increased risk of developing H&N cancer and a 54 per cent greater chance of developing LC. The scientists also found that the rate of cancer increased proportionally to the number of teeth a patient had lost. These increased risks were seen after researchers took into account a patient’s history of smoking and alcohol use.

The researchers noted that age and gender affected the associations between tooth loss and cancer risk. For H&N and OCs, there were clear associations between tooth loss and cancer risk in women and patients younger than 70 years old, but a less clear link in men and older patients. The investigators commented that while widespread inflammation could explain the link between tooth loss and cancer risk, tooth loss in the cancer patients may simply reflect unhealthy behaviours that contribute to cancer risk. Furthermore, people who have lost teeth may not be able to eat a healthy diet, and diet is also a factor in cancer development.

Matthew Dennis - Editor, Cancer Drug News