The FDA today approved Cervarix, a new vaccine to prevent cervical cancer and precancerous lesions caused by human papillomavirus (HPV) types 16 and 18. The vaccine is approved for use in girls and women ages 10 years through 25 years.

Genital HPV infections are the most common sexually-transmitted diseases in the United States, and HPV types 16 and 18 are the cause of about 70 percent of cervical cancers worldwide. There will be an estimated 11,270 new cases and 4,070 deaths from cervical cancer in the United States during 2009, according to the National Cancer Institute at the National Institutes of Health.

“The licensure of Cervarix adds another option in the prevention of cervical cancer” said Karen Midthun, M.D., acting director of the FDA’s Center for Biologics Evaluation and Research. “It has the potential to save lives from cervical cancer as well as reduce the need for biopsies and invasive procedures associated with the necessary follow-up from abnormal Pap tests.”

The primary clinical study for Cervarix included more than 18,000 women ages 15 years through 25 years in the United States and 11 other countries. Of these women, about 9,000 received Cervarix and 9,000 received Havrix, a licensed hepatitis A virus vaccine, as a control.

The results showed that among women who had not already been infected by HPV types 16 and/or 18 before the start of the study, Cervarix was about 93 percent effective in preventing precancerous cervical lesions caused by these HPV types. Among all Cervarix vaccinees, which included those who tested negative for HPV 16 and/or 18, and those who tested positive at the start of the study, Cervarix was approximately 53 percent effective in preventing precancerous cervical lesions.

Studies also were performed to measure the immune response to Cervarix in girls ages 10 years through 14 years. Their immune response was similar to that of women ages 15 years through 25 years, indicating that the vaccine should have similar effectiveness in the 10 through 14 year age group.

The current data show that Cervarix provides protection for about 6.4 years, but additional information on the length of protection is forthcoming.

No vaccine is 100 percent effective, and Cervarix does not protect against HPV infections that an individual may already have at the time of vaccination, nor does Cervarix necessarily protect against those HPV types not in the vaccine. Therefore, regular Pap tests continue to be recommended for all women who receive Cervarix. Pap screening remains critically important to detect precancerous changes, which would allow treatment before cancer develops.

Cervarix contains the adjuvant ASO4. ASO4 is a combination of aluminum hydroxide and monophosphoryl lipid A (MPL) and is the first vaccine licensed by the FDA that includes MPL as an adjuvant. An adjuvant is a substance incorporated into a vaccine that enhances or directs the immune response of the vaccinated individual.

The safety of the vaccine was evaluated in about 24,000 girls and women, with about 13,000 of these receiving Cervarix. The most commonly reported adverse reactions in the Cervarix group included pain, redness, and swelling at the injection site, fatigue, headache, muscle and joint aches, and gastrointestinal distress.

Although Cervarix is not indicated for pregnant women, the FDA is requiring the manufacturer, GlaxoSmithKline Biologicals to conduct a postmarketing study to assess the safety of Cervarix in pregnant women following vaccination prior to identification of pregnancy. Women who are pregnant, or think that they may be pregnant, or plan to become pregnant during the vaccination course, should not use Cervarix.

Cervarix is administered in three separate shots, with the initial dose being followed by two additional shots at one and six months.

Cervarix is manufactured by GlaxoSmithKline Biologicals, based in the United Kingdom.

The initial data from a Phase III study using the Revlimid in multiple myeloma patients who had undergone stem cell transplant reported that the trial had met its primary endpoint of a statistically significant improvement in time to disease progression.

The investigational study evaluated Revlimid compared to placebo in multiple myeloma patients following autologous stem cell transplant, and the independent Data and Safety Monitoring Board reported that the trial had met its primary endpoint of a statistically significant improvement in time to disease progression.

The Phase III, randomized, double-blind, multi-center clinical study was led by the Cancer and Leukemia Group B, or CALGB, and the independent Data and Safety Monitoring Board reported that the trial had met its primary endpoint of a statistically significant improvement in time to disease progression. The study was sponsored by the National Cancer Institute under a Clinical Trials Agreement with Celgene.

Revlimid, in combination with dexamethasone, is already indicated for the treatment of multiple myeloma patients who have received at least one prior therapy.

The Revlimid pivotal MM-015 trial exceeded pre-specified interim efficacy endpoint in newly diagnosed Multiple Myeloma. Further results from the study will be presented in a peer-reviewed setting in 2010.

UK’s drug watchdog National Institute for Clinical Excellence (NICE) has advised against public funding of Tyverb® (lapatinib) on grounds of cost. The drug is a treatment for an aggressive form of advanced breast cancer (ErbB2-positive). Drug makers GSK say they are considering an appeal against the decision.

Lapatinib (in combination with Xeloda® [capecitebine]) offers a new treatment option for women whose disease has returned despite treatment with standard chemotherapies and Herceptin® (trastuzumab).

There are very few treatment options available for these women and lapatinib offers a chance of additional time without their disease progressing. Lapatinib is the only licensed ErbB2 targeted treatment for these patients. Lapatinib can halve the speed of growth of breast cancer in one in five women with an aggressive form of the disease.

It could potentially help about 2,000 women a year with HER2 positive cancer who have run out of options, including the wonder drug Herceptin. But NICE says the NHS cannot afford the cost at £1,600 a month for each patient and lapatinib, also known as Tyverb, should be used only in clinical trials.

The drug makers GlaxoSmithKline (GSK) is giving the first three months of treatment free, with the NHS picking up the bill for those who respond and need it for longer.

Simon Jose, General Manager, GSK UK commented; “We disagree with the NICE decision and believe Tyverb is a valuable and important treatment for eligible women. In recognition of the cost effectiveness challenges with drugs that treat patients with a short life expectancy, we offered the Tyverb Patient Access Programme to help ensure it was made available on the NHS. It is difficult to comment without the appearance of self interest. However, there is clearly more work to be done by all parties when flexible access programmes from industry and the recent changes by NICE for patients with a short life expectancy still fail to give them access to valuable medicines.”

GSK proposed the patient access programme in the UK when NICE indicated early on in its review that it did not consider lapatinib to be cost effective in treating this patient population. In an effort to achieve a positive outcome for patients and greater value to the NHS, GSK bears the cost of lapatinib, for all eligible patients under the scheme, for up to the first 12 weeks of treatment. The NHS would commence payment only for the patients who continue to receive clinical benefit beyond 12 weeks.  GSK will continue to honour the patient access programme for NHS trusts in the UK.

During the lapatinib assessment, NICE proposed new advice for the assessment of treatments in small patient populations with a short life expectancy. Lapatinib is licensed for a particular type of breast cancer that affects around 2000 women a year. Therefore lapatinib qualified for review under the new advice.

GSK submitted a sub-group analysis that met the overall survival (OS) criterion of this new NICE advice. However NICE concluded that whilst the data analysis could be useful in guiding future research, as it stands it would not change their conclusions.

NICE’s decision reflects the difficulty in demonstrating significant survival benefits in patients at this advanced stage of disease, the drug-makers said Furthermore, trials are often halted early for ethical reasons to allow patients to cross over to the active arm because of the effectiveness demonstrated by the medicine under study, as in the case of lapatinib.

In its final appraisal determination, NICE acknowledges that lapatinib is a clinically effective option, noting that lapatinib plus capecitabine demonstrated improved time to progression (TTP) and progression free survival (PFS) –  significantly delaying the progression of the cancer and controlling the disease.

GSK’s NICE submission demonstrated that lapatinib, in conjunction with the patient access programme, could actually save the NHS money in patients who would have received trastuzumab (Herceptin®) containing regimens. NICE acknowledged this is the majority (>50%) of eligible patients, however NICE concluded that trastuzumab is not likely to be cost effective in this setting and therefore lapatinib plus capecitabine would not be cost effective.

Inspirational fundraiser Jane Tomlinson, who died in September 2007 aged 43, was among hundreds of British women who got the drug thanks to an ‘expanded access’ programme paid for by GSK. Mrs Tomlinson lost her seven-year battle with cancer after raising more than £1.75 million for charity in gruelling endurance events, including three London Marathons. Mrs Tomlinson’s widower Mike condemned the ban when it was first proposed earlier this year, saying Nice had failed the ‘acid test’.

He said ‘We know what a difference it made to Jane. Initially she was refused the drug so by the time she got it, she was desperately ill but we saw the benefits and the good effects’. Jane would be absolutely furious about this and it seems illogical. Considering the small number of women who would be eligible, it’s a small price to pay.

‘This drug is routinely used in other European countries. Have they got it wrong or do they have better healthcare than us?’

Dr Alison Jones, medical oncologist at the University College London Hospital and the Royal Free Hospital, said ‘I am disappointed for all the women who would have benefited from lapatinib on the NHS. ‘I have witnessed myself that lapatinib can extend the lives of these women. We are now left with very few effective treatment options in cases where Herceptin has stopped working.’

The decision from NICE is the final stage of its consultation process and, subject to appeal, guidance will be issued later this year.