Cervical cancer vaccine market hots up in India with Merck’s Gardasil and GSK’s Cervarix

Merck’s Gardasil and GSK’s Cervarix cervical cancer vaccines are poised for a tough battle in India.

Cervical cancer vaccine makers are betting big on India as the deadly cancer takes the lives of 8 women in India every hour.

WHO estimates that each year over 1.30 lakh Indian women are diagnosed with cervical cancer and over 74,000 die of cervical cancer .

Cervical cancer or cancer of the uterine cervix, is the most common type of cancer affecting women in India.

Worldwide, it was the second-most common cancer after breast cancer.

Glaxo’s head-to-head study, named HPV-010, measures which vaccine caused greater immune system response in more than 1,000 women seven months after the shot.

Causes of cervical cancer

Cervical cancer is a serious disease that can be life-threatening. This disease is caused by certain high-risk HPV types that can cause the cells in the lining of the cervix to change from normal to precancerous lesions. If these precancerous lesions are not diagnosed early and treated, they may turn cancerous after a few years.

Every year, almost 74,000 women die due to Cervical cancer in India, which is more than one fourth of the world deaths due to Cervical cancer. Woman in India have a 2.5% life time risk to get Cervical Cancer, which is double the risk as compared to the data worldwide (1.3%).

Though there is no known cure for cervical cancer, the recent advances in vaccine technology have made it more or less certain that cervical cancer can be prevented in majority of cases using vaccine.

The human papillomavirus, also called HPV, was a common pathogen predominantly affecting women. Approximately 80 per cent of women get one or more types of virus by the age of 50.

Reportedly, there are more than 100 types of HPV. Of these, about 15 high-risk types were known to cause virtually all cases of cervical cancer. “Two of these types (16 and 18) are believed to cause 70 per cent of these cases (76.7 per cent in Indian women).

Though there is no known cure for cervical cancer, the recent advances in vaccine technology have made it more or less certain that cervical cancer can be prevented in majority of cases using vaccine. The global market for cervical vaccine is estimated at more than $10 billion last year.

MSD Pharmaceuticals (India), the local affiliate of Merck & Co., Inc USA launched Gardasil a quadrivalent human papillomavirus vaccine.Gardasil is the only vaccine that helps protect against 4 types – types 6, 11, 16, 18 – of HPV. The vaccine helps prevent diseases such as cervical cancer; abnormal and precancerous cervical lesions, vaginal lesions, vulvar lesions; and genital warts, caused by these types of HPV, MSD said while announcing the launch.

Gardasil is recommended to be given to females aged between 9 to 26 years.

Announcing the launch, Dr. Naveen A. Rao, managing director, MSD India, said, “ With the launch of Gardasil,we have initiated the war against Cervical Cancer, the number one cause of mortality amongst Indian women due to cancer. In line with our commitment to putting patients first, MSD India will work with partners and communities to enhance awareness for the disease and access for the vaccine.”

The placebo controlled, double blind, randomized, multicentric studies done in more than 20,000 females across 5 continents show that in women who did not have evidence of exposure to HPV types contained in the vaccine Gardasil provides 98% protection against cervical pre-cancers caused by HPV types 16 & 18, which are responsible for 70% of all Cervical Cancer cases worldwide, said Dr. Neerja Bhatla from the All India Institute of Medical Sciences (AIIMS, New Delhi).

Similarly, in large placebo controlled, double blind, randomized, multicentric studies, the vaccine has also been proven to be 99% effective in the prevention of genital warts caused by HPV types 6 and 11, which are responsible for 90% of all genital warts cases worldwide. In India the number of cases is increasing every year.

“This is a very promising breakthrough but women must remember that they still need to visit their doctors for regular screening for cervical and other cancers” she added.

HPV vaccination is now unequivocally recommended by the IAP Committee of Immunization (COI) for females over the age of ten. This decision is based on expected high impact on public health in future as it will help prevent mortality due to cervical cancer in women in their prime age and keep families united and safe.

According to the Indian Academy of Pediatrics Committee of Immunization (IAPCOI) 2008 recommendations: “This vaccine has a favorable tolerability profile and the IAP-COI recommends offering HPV vaccine to all females as per label. The recommended age for initiation of vaccination is 10-12 years and catch up vaccination is permitted up to the age of 26 years. It is recommended to be given in three doses at 0, 2 and 6 months.”

Merck’s Gardasil: Precautions & Side-effects

Gardasil contains recombinant virus like particle (VLPs) assembled from the L1 proteins of HPVs 6, 11, 16 and 18. Since VLPs lack the viral DNA, they cannot induce cancer. They do, however, trigger an antibody response that protects vaccine recipients from becoming infected with the HPV types represented in the vaccine.

As per available data, till February 2009, 40 million doses of Gardasil had been distributed worldwide. There is no evidence the vaccine has caused serious adverse effects. According to the Centers for Disease Control, the vaccine was tested in over 11,000 women and girls (ages 9 to 26).

Fainting is more common among adolescents receiving the Gardasil vaccine than in other kinds of vaccinations. Patients should remain seated for 15 minutes after they receive the HPV vaccine. It is also reported that the shot is more painful than other common vaccines. General side effects of Gardasil may include joint and muscle pain, fatigue, physical weakness and general malaise.

Gardasil cannot be taken if you have or have had an allergic reaction after getting a dose of Gardasil or  a severe allergic reaction to yeast, amorphous aluminum hydroxyphosphate sulfate, polysorbate.

Gardasil is not recommended for use in pregnant women,  have immune problems, like HIV infection, cancer, or you take medicines that affect your immune system,  have a fever over 100°F (37.8°C)

Gardasil is a shot that is usually given in the arm muscle. Three shots are given on the following schedule:

• Dose 1: at a date you and your health care provider choose.

• Dose 2: 2 months after Dose 1.

• Dose 3: 6 months after Dose 1.

Gardasil, sold in 109 countries, generated $1.4 billion for Merck.

Sales of Gardasil fell 33 percent worldwide to $262 million and 39 percent in the U.S. in the first quarter, Merck said. Gardasil, approved in 2006 in girls and women ages 9 to 26, hasn’t been embraced for older girls within that age group, Merck said.

MSD India is collaborating with the Indian Council of Medical Research, as a public-private partnership to bring Cervical Cancer vaccine to the Indian public sector at an affordable price.

GlaxoSmithKline’s Cervarix cervical cancer vaccine

Similarly, GlaxoSmithKline is also planning a large-scale launch its cervical cancer vaccine Cervarix in India.

Cervarix is a vaccine against certain types 16 and 18, which currently cause about 70% of cervical cancer cases.

Cervarix is a preventative cervical cancer vaccine, not therapeutic. Cervarix vaccine will not block infection from cervical cancer-causing HPV strains other than HPV 16, 18, 31 and 45

Developed  by researchers at Georgetown University Medical Center, the University of Rochester, the University of Queensland in Australia, and the U.S. National Cancer Institute Cervarix is using the L1 protein of the viral capsid. Recombinant activity in a baculovirus vector produces L1 protein spheres, which are very immunogenic. The viral proteins induce the formation of neutralizing antibodies. The vaccine contains no live virus and no DNA, so it cannot infect the patient.

Cervaris data from patients show that at 18 months after the first of a three-dose regimen, 100 percent of women up to age 55 vaccinated with Cervarix vaccine had antibodies present against the two most common cancer-causing human papillomavirus types, 16 and 18.

Phase 3 trial data also suggest that the vaccine, formulated with a proprietary adjuvant system called AS04, is highly immunogenic and generally well-tolerated, with antibody levels at least 10 times greater than those produced by natural infection.

Cervarix study showed that antibody levels in women ages 26 to 55 against cancer-causing virus types 16 and 18 were in the same range as observed in a separate study. That study demonstrated that the GSK cervical cancer vaccine provided 100 percent sustained protection against precancerous lesions caused by these virus types for up to 5.5 years in women ages 15 to 25.

Gardasil Sales

Cervarix vaccine is approved and sold in more than 60 countries, including Australia (for women ages 10 to 45),  Philippines and European Union, among other countries. Cervarix had sales of 125 million pounds ($182 million) last year. Cervarix has received approval by the UK government for its national programme of vaccination for teenage girls. Glaxo has also won exclusive contracts to provide Cervarix to young girls and women in the Netherlands and the U.K.

Cervarix  is awaiting approval in United States of America. On March 29, 2007 GlaxoSmithKline submitted a Biologics License Application (BLA) for Cervarix to the FDA. However, US FDA sought more data and GSK awaiting results of further trials to submit to the FDA. Approval is not expected before late 2009.

Sales for Glaxo’s Cervarix amount to less than 10 percent of those garnered by Merck’s similar vaccine.

Cervarix Vs. Gardasil: Which is the better cervical cancer vaccine?

Cervarix  is bivalent –effective against only two strains of the virus –vaccine. While  Gardasil is quadrivalent vaccine (effective against four common strains of HPV).

The question now arises which vaccine to be the vaccine of choice.

1. On the face of it a quadrivalent vaccine seems to be the better choice. In reality that is not so. The vaccine protects against the HPV viruses 16,18, 6, 11, of which only the first two are responsible for cervical cancer, while the other two are responsible for genital warts.
2. On the other hand Cervarix gives protection against 16 and 18. It is better because, there is cross-reactive protection against the virus strains 45 and 31, two other viruses causing cervical cancer.
3. Cervarix is formulated with AS04, a propriety adjuvant that boosts the immune system response for a longer period of time.
4. Both vaccines are against the human papilloma virus but Cervarix seems to be more effective against cancer cervix.
5. Cervarix can be given to females between 10 to 45 yrs old, whereas Gardasil can be given to females between 16 to 26yrs only.
6. Both the vaccines are given in the schedule of 0,1,6 months. Cervarix is the costlier one being priced at Rs.3200 per dose. Cervarix seems to win against Gardasil because of its stronger immune response and broader protection.

Though there is no clinical data comparing the efficacy of both Garadasil and Cervarix, GlaxoSmithKline Plc is planning to release the first study to compare its cervical cancer vaccine with Merck & Co.’s blockbuster Gardasil.

Glaxo also plans to release another key Cervarix study, known as HPV-008, which tracks the effect of the vaccine on more than 18,600 women.

Glaxo’s head-to-head study, named HPV-010, measures which vaccine caused greater immune system response in more than 1,000 women seven months after the shot.