GARDASIL(R), Merck's Cervical Cancer Vaccine, Receives Positive Opinion from the European Medicines Agency.

WHITEHOUSE STATION, N.J. -- Merck & Co., Inc. announced today that GARDASIL(R) (quadrivalent human papillomavirus types 6, 11, 16, 18, recombinant vaccine), has received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) in Europe. The CHMP opinion recommends that GARDASIL be approved for the immunization of children and adolescents aged 9 to 15 years and of adult females aged 16 to 26 years for the prevention of cervical cancer, high-grade cervical dysplasia (CIN 2/3), high-grade vulvar dysplastic lesions (VIN 2/3) and external genital warts caused by human papillomavirus types 6, 11, 16 and 18. Following the CHMP review, the opinion for GARDASIL is transmitted to the European Commission (EC). If the EC approves the opinion, the EC then deliberates on the decision for approval. This decision will be applicable to the 25 countries that are members of the European Union (EU), of which the five largest are the United Kingdom, Germany, France, Italy and Spain.

GARDASIL will be marketed by Sanofi Pasteur MSD (SPMSD), a joint venture between Sanofi Pasteur and Merck & Co., Inc., Whitehouse Station, New Jersey, USA, in EU countries covered by the joint venture and several other European countries. In the remaining European countries, located in central and eastern Europe, GARDASIL will be marketed by Merck Sharp & Dohme as either GARDASIL or SILGARD(R).

Worldwide Availability of GARDASIL

On June 8, the FDA approved GARDASIL to prevent cervical cancer and vaginal and vulvar pre-cancers caused by human papillomavirus (HPV) types 16 and 18 and to prevent low-grade and pre-cancerous lesions and genital warts caused by HPV types 6, 11, 16 and 18. GARDASIL is approved in the United States for 9- to 26-year-old girls and women. GARDASIL is approved for use in the U.S., Mexico, Australia, Canada and New Zealand. Additional applications for GARDASIL are currently under review with regulatory agencies in more than 50 countries around the world. Additionally, Merck is actively working to accelerate the availability of GARDASIL in the developing world: in December, Merck announced a partnership with India's Council of Medical Research to study GARDASIL. Merck is also working with PATH and the Gates Foundation to develop HPV vaccination programs that will facilitate the introduction of GARDASIL to the most impoverished nations. Merck will make our new vaccines, including GARDASIL, available at dramatically lower prices to developing world countries.

Selected important information about GARDASIL

GARDASIL is contraindicated in individuals who are hypersensitive to the active substances or to any of the excipients of the vaccine. As with any vaccine, vaccination with GARDASIL may not result in protection in all vaccine recipients. GARDASIL is not intended to be used for treatment of active genital warts; cervical cancer; CIN, VIN, or VaIN. GARDASIL has not been shown to protect against disease due to non-vaccine HPV types. The health-care provider should inform the patient, parent, or guardian that vaccination does not substitute for routine cervical cancer screening. Women who receive GARDASIL should continue to undergo cervical cancer screening per standard of care.

Vaccine-related adverse experiences that were observed in clinical trials at a frequency of at least 1.0 percent among recipients of GARDASIL and also greater than those observed among recipients of placebo, respectively, were pain (83.9 percent vs. 75.4 percent), swelling (25.4 percent vs. 15.8 percent), erythema (24.6 percent vs. 18.4 percent), fever (10.3 percent vs. 8.6 percent), and pruritis (3.1 percent vs. 2.8 percent).

Other Information about GARDASIL

In 1995, Merck entered into a license agreement and collaboration with CSL Limited relating to technology used in GARDASIL. GARDASIL also is the subject of other third-party licensing agreements.

About Merck

Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck currently discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The Company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. For more information, visit www.merck.com.

Forward-Looking Statement

This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements are based on management's current expectations and involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential or financial performance. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Merck's business, particularly those mentioned in the cautionary statements in Item 1 of Merck's Form 10-K for the year ended Dec. 31, 2005, and in its periodic reports on Form 10-Q and Form 8-K, which the Company incorporates by reference.

GARDASIL(R) and SILGARD(R) are registered trademarks of Merck & Co., Inc., Whitehouse Station, N.J., U.S.A.

Full U.S. Prescribing Information and Patient Product Information is attached and is also available at www.gardasil.com

 
MERCK & CO., INC. 
Whitehouse Station, NJ 08889, USA                              9682300 
---------------------------------------------------------------------- 
 
GARDASIL(R) 
(Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant 
Vaccine) 
 
DESCRIPTION 
 
    GARDASIL* is a non-infectious recombinant, quadrivalent vaccine 
prepared from the highly purified virus-like particles (VLPs) of the 
major capsid (L1) protein of HPV Types 6, 11, 16, and 18. The L1 
proteins are produced by separate fermentations in recombinant 
Saccharomyces cerevisiae and self-assembled into VLPs. The 
fermentation process involves growth of S. cerevisiae on 
chemically-defined fermentation media which include vitamins, amino 
acids, mineral salts, and carbohydrates. The VLPs are released from 
the yeast cells by cell disruption and purified by a series of 
chemical and physical methods. The purified VLPs are adsorbed on 
preformed aluminum-containing adjuvant (amorphous aluminum 
hydroxyphosphate sulfate). The quadrivalent HPV VLP vaccine is a 
sterile liquid suspension that is prepared by combining the adsorbed 
VLPs of each HPV type and additional amounts of the 
aluminum-containing adjuvant and the final purification buffer. 
    GARDASIL is a sterile preparation for intramuscular 
administration. Each 0.5-mL dose contains approximately 20 mcg of HPV 
6 L1 protein, 40 mcg of HPV 11 L1 protein, 40 mcg of HPV 16 L1 
protein, and 20 mcg of HPV 18 L1 protein. 
    Each 0.5-mL dose of the vaccine contains approximately 225 mcg of 
aluminum (as amorphous aluminum hydroxyphosphate sulfate adjuvant), 
9.56 mg of sodium chloride, 0.78 mg of L-histidine, 50 mcg of 
polysorbate 80, 35 mcg of sodium borate, and water for injection. The 
product does not contain a preservative or antibiotics. 
    After thorough agitation, GARDASIL is a white, cloudy liquid. 
 
CLINICAL PHARMACOLOGY 
 
Disease Burden 
 
    Human Papillomavirus (HPV) causes squamous cell cervical cancer 
(and its histologic precursor lesions Cervical Intraepithelial 
Neoplasia (CIN) 1 or low grade dysplasia and CIN 2/3 or moderate to 
high grade dysplasia) and cervical adenocarcinoma (and its precursor 
lesion adenocarcinoma in situ (AIS)). HPV also causes approximately 
35-50% of vulvar and vaginal cancers. Vulvar Intraepithelial Neoplasia 
(VIN) Grade 2/3 and Vaginal Intraepithelial Neoplasia (VaIN) Grade 2/3 
are immediate precursors to these cancers. 
    Cervical cancer prevention focuses on routine screening and early 
intervention. This strategy has reduced cervical cancer rates by 
approximately 75% in compliant individuals by monitoring and removing 
premalignant dysplastic lesions. 
    HPV also causes genital warts (condyloma acuminata) which are 
growths of the cervicovaginal, vulvar, and the external genitalia that 
rarely progress to cancer. HPV 6, 11, 16, and 18 are common HPV types. 
    HPV 16 and 18 cause approximately: 
 
    --  70% of cervical cancer, AIS, CIN 3, VIN 2/3, and VaIN 2/3 
        cases; and 
 
    --  50% of CIN 2 cases. 
 
    HPV 6, 11, 16, and 18 cause approximately: 
 
    --  35 to 50% of all CIN 1, VIN 1, and VaIN 1 cases; and 
 
    --  90% of genital wart cases. 
 
Mechanism of Action 
 
    HPV only infects humans, but animal studies with analogous 
(animal, not human) papillomaviruses suggest that the efficacy of L1 
VLP vaccines is mediated by the development of humoral immune 
responses. 
 
    CLINICAL STUDIES 
 
    CIN 2/3 and AIS are the immediate and necessary precursors of 
squamous cell carcinoma and adenocarcinoma of the cervix, 
respectively. Their detection and removal has been shown to prevent 
cancer; thus, they serve as surrogate markers for prevention of 
cervical cancer. 
    Efficacy was assessed in 4 placebo-controlled, double-blind, 
randomized Phase II and III clinical studies. The first Phase II study 
evaluated the HPV 16 component of GARDASIL (Protocol 005, N = 2391) 
and the second evaluated all components of GARDASIL (Protocol 007, N = 
551). The Phase III studies, termed FUTURE (Females United To 
Unilaterally Reduce Endo/Ectocervical Disease), evaluated GARDASIL in 
5442 (FUTURE I or Protocol 013) and 12,157 (FUTURE II or Protocol 015) 
subjects. Together, these four studies evaluated 20,541 women 16 to 26 
years of age at enrollment. The median duration of follow-up was 4.0, 
3.0, 2.4, and 2.0 years for Protocol 005, Protocol 007, FUTURE I, and 
FUTURE II, respectively. Subjects received vaccine or placebo on the 
day of enrollment, and 2 and 6 months thereafter. Efficacy was 
analyzed for each study individually and for all studies combined 
according to a prospective clinical plan. 
 
Prophylactic Efficacy 
 
    GARDASIL is designed to prevent HPV 6-, 11-, 16-, and/or 
18-related cervical cancer, cervical dysplasias, vulvar or vaginal 
dysplasias, or genital warts. GARDASIL was administered without 
prescreening for presence of HPV infection and the efficacy trials 
allowed enrollment of subjects regardless of baseline HPV status 
(i.e., Polymerase Chain Reaction (PCR) status or serostatus). Subjects 
who were infected with a particular vaccine HPV type (and who may 
already have had disease due to that infection) were not eligible for 
prophylactic efficacy evaluations for that type. 
    The primary…