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October 10, 2017 7:00 am ET

Merck’s 20-year commitment to HPV research highlighted in oral session

Merck (NYSE:MRK), known as MSD outside of the United States and Canada,
announced results from final analyses of the pivotal Phase III efficacy,
immunogenicity, and safety clinical trial for GARDASIL^® 9
(Human Papillomavirus 9-valent Vaccine, Recombinant). The data, which
showed sustained efficacy for up to six years in the per protocol
population, were presented during an oral session at the European
Research Organization on Genital Infection and Neoplasia (EUROGIN)
congress in Amsterdam, Netherlands.

GARDASIL 9 is a vaccine indicated for use in girls and women 9 through
26 years of age for the prevention of cervical, vulvar, vaginal, and
anal cancers caused by HPV types 16, 18, 31, 33, 45, 52, and 58;
pre-cancerous or dysplastic lesions caused by HPV types 6, 11, 16, 18,
31, 33, 45, 52, and 58; and genital warts caused by HPV types 6 and 11.
GARDASIL 9 is also indicated for use in boys and men 9 through 26 years
of age for the prevention of anal cancer caused by HPV types 16, 18, 31,
33, 45, 52, and 58; precancerous or dysplastic lesions caused by HPV
types 6, 11, 16, 18, 31, 33, 45, 52, and 58; and genital warts caused by
HPV types 6 and 11. GARDASIL 9 is contraindicated in individuals with
hypersensitivity, including severe allergic reactions to yeast, or after
a previous dose of GARDASIL 9 or GARDASIL^® [Human
Papillomavirus Quadrivalent (types 6, 11, 16, and 18) Vaccine,
Recombinant].

These final analyses evaluated study outcomes, including efficacy for up
to six years following receipt of first vaccine dose, and antibody
responses over five years. Vaccination impact on cervical cytology
abnormalities and related therapeutic procedures were also reported.
These final analyses are from the base study; a study extension is
ongoing to evaluate long term follow-up for an additional 10 years
following the end of the base study.

In these analyses at six years, efficacy for GARDASIL 9 against
HPV31/33/45/52/58-related cervical pre-cancers (cervical intraepithelial
neoplasia Grade 3 (CIN 3) was 100 percent (95% CI: 39·4, 100) in the
per-protocol population. Efficacy against HPV type
31/33/45/52/58-related cervical, vulvar, and vaginal disease, persistent
infection, cervical cytological abnormalities; cervical biopsy; and
cervical definitive therapy ranged from 90-98 percent. Incidence of
HPV6/11/16/18-related persistent infection, disease, cytological
abnormalities, and procedures was similar in recipients of GARDASIL 9
(Human Papillomavirus 9-valent Vaccine, Recombinant) and GARDASIL [Human
Papillomavirus Quadrivalent (Types 6, 11, 16 and 18) Vaccine,
Recombinant].

GARDASIL 9 produced similar antibody protection against the four HPV
types in GARDASIL. Antibodies to the HPV types targeted by GARDASIL 9
persisted through five years following vaccination. Geometric mean titer
ratios (GARDASIL 9/GARDASIL) for HPV6/11/16/18 varied minimally over
time. The two vaccines had similar adverse event profiles;
injection-site adverse events were more common with GARDASIL 9; most
were mild-to-moderate in intensity. A paper detailing these results was
also published online on September 5 in The Lancet.

“These new analyses show that efficacy of GARDASIL 9 in preventing
certain HPV-related cancers and diseases was sustained for up to six
years,” said Elmar A. Joura, M.D., Associate Professor of Gynecology and
Obstetrics at the Medical University of Vienna, General Hospital (AKH),
and Comprehensive Cancer Center Vienna, Austria, who presented these
data at EUROGIN. “Despite the progress we’ve made with HPV vaccination
over the past 11 years, HPV-related cancers and diseases are still a
significant public health issue and continued efforts are needed to
increase uptake of the vaccine.”

About the study

The clinical trial program for GARDASIL 9 was designed to build upon the
efficacy established in clinical trials with GARDASIL. In this Phase III
active comparator-controlled, double-blind, randomized clinical trial
(Protocol 001), 14,215 females 16-26 years of age were randomized to
receive a three-dose series of GARDASIL 9 (n=7,106) or GARDASIL
(n=7,109). The primary comparison between GARDASIL 9 and GARDASIL was
clinical efficacy for the five additional HPV types. Efficacy of
GARDASIL 9 against persistent infection and disease related to the
original four HPV types (6, 11, 16, or 18) was inferred based on
immunogenicity comparisons. The primary efficacy analysis was conducted
in those who received all three doses of vaccine within one year of
enrollment, did not have deviations from the study protocol that could
affect the evaluation of vaccine efficacy, were negative (PCR negative
and seronegative) to the relevant HPV type(s) prior to dose 1, and who
remained PCR negative to the relevant HPV type(s) through Month 7
(per-protocol efficacy, or PPE, population).

The primary efficacy evaluation was based on a composite clinical
endpoint of HPV 31-, 33-, 45-, 52-, and 58-related cervical, vulvar, and
vaginal cancer, and high-grade cervical/vulvar/vaginal disease [CIN 2/3
(cervical intraepithelial neoplasia 2/3) or AIS (adenocarcinoma in
situ), VIN 2/3 (vulvar intraepithelial neoplasia 2/3), and VaIN 2/3
(vaginal intraepithelial neoplasia 2/3)]. Additional secondary endpoints
related to HPV 31, 33, 45, 52, and 58 were also evaluated. Efficacy for
all endpoints was measured starting after the Month 7 visit.

Efficacy of GARDASIL 9 against persistent infection and disease related
to HPV types 6, 11, 16, or 18 was inferred from non-inferiority
comparisons of geometric mean titers (GMTs) in 16- through 26-year-old
girls and women following vaccination with GARDASIL 9 with those
following vaccination with GARDASIL [Human Papillomavirus Quadrivalent
(Types 6, 11, 16, and 18) Vaccine, Recombinant]. Antibody responses for
HPV 6, 11, 16, and 18 (measured by GMTs and seroconversion rates at
Month 7) for GARDASIL 9 among young women 16 to 26 years of age were
non-inferior to those who received GARDASIL.

Important Information about GARDASIL 9 (Human Papillomavirus 9-valent
Vaccine, Recombinant)

GARDASIL 9 does not eliminate the necessity for women to continue to
undergo recommended cervical cancer screening. Recipients of GARDASIL 9
should not discontinue anal cancer screening if it has been recommended
by a health care professional.

GARDASIL 9 has not been demonstrated to provide protection against
diseases from vaccine HPV types to which a person has previously been
exposed through sexual activity.

GARDASIL 9 is not a treatment for external genital lesions; cervical,
vulvar, vaginal, and anal cancers; or CIN; VIN; VaIN; or AIN.

Not all vulvar, vaginal, and anal cancers are caused by HPV, and
GARDASIL 9 protects only against those vulvar, vaginal, and anal cancers
caused by HPV 16, 18, 31, 33, 45, 52, and 58.

Vaccination with GARDASIL 9 may not result in protection in all vaccine
recipients.

Select Safety Information for GARDASIL 9

GARDASIL 9 is contraindicated in individuals with hypersensitivity,
including severe allergic reactions to yeast, or after a previous dose
of GARDASIL 9 or GARDASIL.

Because vaccinees may develop syncope, sometimes resulting in falling
with injury, observation for 15 minutes after administration is
recommended. Syncope, sometimes associated with tonic-clonic movements
and other seizure-like activity, has been reported following HPV
vaccination. When syncope is associated with tonic-clonic movements, the
activity is usually transient and typically responds to restoring
cerebral perfusion.

Safety and effectiveness of GARDASIL 9 have not been established in
pregnant women.

The most common (≥10%) local and systemic adverse reactions in females
were injection-site pain, swelling, erythema, and headache. The most
common (≥10%) local and systemic reactions in males were injection-site
pain, swelling, and erythema.

The duration of immunity with GARDASIL 9 has not been established.

About GARDASIL

^®

9 (Human Papillomavirus
9-valent Vaccine, Recombinant)

GARDASIL 9 includes the greatest number of HPV types in any available
HPV vaccine. After HPV types 16 and 18, the five additional HPV types in
GARDASIL 9 are the most common cervical cancer-causing types worldwide.
Seven HPV types in GARDASIL 9 (HPV 16, 18, 31, 33, 45, 52 and 58) cause
approximately 90 percent of cervical cancer cases and approximately 80
percent of high-grade cervical lesions (cervical precancers, defined as
CIN 2, CIN 3 and AIS) worldwide. These seven HPV types also cause 85-90
percent of HPV-related vulvar cancers, 80-85 percent of HPV-related
vaginal cancers, and 90-95 percent of HPV-related anal cancers. HPV
types 6 and 11 cause approximately 90 percent of genital warts cases. In
addition, approximately 50 percent of cases of low-grade cervical
lesions (CIN 1) are caused by the nine HPV types included in the vaccine.

GARDASIL 9 is approved for use in more than 60 countries, and since 2015
more than 26 million doses have been distributed worldwide, although the
exact number of doses that have been administered is unknown. GARDASIL
[Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine,
Recombinant] is no longer available in the United States.

Dosage and administration for GARDASIL 9

GARDASIL 9 should be administered intramuscularly in the deltoid region
of the upper arm or in the higher anterolateral area of the thigh.

• For individuals 9 through 14 years of age, GARDASIL 9 can be
  administered using a
  2-dose or 3-dose schedule. For the 2-dose
  schedule, the second dose should be administered 6-12 months after the
  first dose. If the second dose is administered less than 5 months
  after the first dose, a third dose should be given at least 4 months
  after the second dose. For the 3-dose schedule, GARDASIL 9 should be
  administered at 0, 2 months, and 6 months.
• For individuals 15 through 26 years of age, GARDASIL 9 is administered
  using a
  3-dose schedule at 0, 2 months, and 6 months.

20-year commitment to HPV vaccine research

Prof. Anna Giuliano of Moffitt Cancer Center in Tampa, Fla. presented a
review of Merck’s 20-year history of HPV vaccine research during an oral
session at EUROGIN. Merck’s proof-of-principle studies with monovalent
HPV vaccines in 1997 were followed in 2000 with the start of clinical
studies for the quadrivalent HPV vaccine, GARDASIL [Human Papillomavirus
Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant]. First
regulatory approvals of GARDASIL were received in 2006. Studies have
continued to evaluate duration of protection as well as safety.

HPV types 16 and 18 cause approximately 70 percent of cervical cancer
cases. In 2004, HPV types 31, 33, 45, 52, and 58 were classified as the
next most frequent HPV types associated with cervical cancer, causing an
additional 20 percent of cases. Merck started a Phase II study in 2005
to evaluate a HPV vaccine candidate that could protect against more HPV
types. Ultimately this led to the development of the 9-valent HPV
vaccine, GARDASIL 9 (Human Papillomavirus 9-valent Vaccine,
Recombinant), which helps to protect against certain cancers and
diseases caused by these five HPV types in addition to the four original
HPV types covered by GARDASIL. Phase III clinical studies for GARDASIL
9, which evaluated more than 20,000 individuals who received the
vaccine, began in 2007, just one year after GARDASIL was licensed.

“Merck has had a sustained and unwavering commitment to HPV vaccine
research for 20 years,” said Eliav Barr, MD, senior vice president,
Global Clinical Development – Infectious Disease & Vaccines, Merck
Research Laboratories. “With HPV vaccination, screening, treatment, and
education, it is our aspiration that one day the number of women and men
affected by HPV-related cancers and diseases will be significantly
reduced. There is obviously much work ahead of us, but we look forward
to continuing our efforts in collaboration with the many stakeholders
around the world who share our commitment.”

About HPV and related cancers and diseases

In the United States, human papillomavirus (HPV) will infect most
sexually active males and females in their lifetime. According to the
CDC, there are approximately 14 million new genital HPV infections in
the United States each year, half of which occur in people 15 through 24
years of age. For most people, HPV clears on its own, but for others who
don’t clear the virus it could lead to certain cancers and other
diseases in males as well as females. There is no way to predict who
will or won’t clear the virus.

HPV causes virtually all cervical cancer cases. Each day, about 35 women
are diagnosed with cervical cancer in the United States — about 12,900
women per year. HPV also causes approximately 70-75 percent of vaginal
cancer cases and approximately 30 percent of vulvar cancer cases in
females, and approximately 85-90 percent of anal cancers and 90 percent
of genital warts in both females and males. Additionally, there are an
estimated 3 million abnormal Pap results, many of which are caused by
HPV, that require follow-up each year in the United States.

Anal cancer and genital warts affect both men and women. According to
the American Cancer Society, an estimated 2,920 men and 5,160 women in
the United States will be diagnosed with anal cancer in 2016, and
overall rates have been increasing. There is no routine screening
recommended for the general population to reduce the risk of anal
cancer. Approximately 355,000 cases of genital warts occur each year in
the United States. Treatment of genital warts can be painful, and they
may recur after treatment, especially in the first three months.
Approximately 3 out of 4 people get them after having genital contact
with someone who has genital warts.

About Merck

For more than a century, Merck, a leading global biopharmaceutical
company known as MSD outside of the United States and Canada, has been
inventing for life, bringing forward medicines and vaccines for many of
the world’s most challenging diseases. Through our prescription
medicines, vaccines, biologic therapies and animal health products, we
work with customers and operate in more than 140 countries to deliver
innovative health solutions. We also demonstrate our commitment to
increasing access to health care through far-reaching policies, programs
and partnerships. Today, Merck continues to be at the forefront of
research to advance the prevention and treatment of diseases that
threaten people and communities around the world – including cancer,
cardio-metabolic diseases, emerging animal diseases, Alzheimer’s disease
and infectious diseases including HIV and Ebola. For more information,
visit www.merck.com
and connect with us on Twitter,
Facebook,
Instagram,
YouTube
and LinkedIn.

Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USA

This news release of Merck & Co., Inc., Kenilworth, N.J., USA (the
“company”) includes “forward-looking statements” within the meaning of
the safe harbor provisions of the U.S. Private Securities Litigation
Reform Act of 1995. These statements are based upon the current beliefs
and expectations of the company’s management and are subject to
significant risks and uncertainties. If underlying assumptions prove
inaccurate or risks or uncertainties materialize, actual results may
differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, general industry
conditions and competition; general economic factors, including interest
rate and currency exchange rate fluctuations; the impact of
pharmaceutical industry regulation and health care legislation in the
United States and internationally; global trends toward health care cost
containment; technological advances, new products and patents attained
by competitors; challenges inherent in new product development,
including obtaining regulatory approval; the company’s ability to
accurately predict future market conditions; manufacturing difficulties
or delays; financial instability of international economies and
sovereign risk; dependence on the effectiveness of the company’s patents
and other protections for innovative products; and the exposure to
litigation, including patent litigation, and/or regulatory actions.

The company undertakes no obligation to publicly update any
forward-looking statement, whether as a result of new information,
future events or otherwise. Additional factors that could cause results
to differ materially from those described in the forward-looking
statements can be found in the company’s 2016 Annual Report on Form 10-K
and the company’s other filings with the Securities and Exchange
Commission (SEC) available at the SEC’s Internet site (www.sec.gov).

Please see Prescribing Information for GARDASIL

^®


9 (Human Papillomavirus 9-valent Vaccine, Recombinant) at

http://www.merck.com/product/usa/pi_circulars/g/gardasil_9/gardasil_9_pi.pdf


and Patient Product Information for GARDASIL

^®

9
at

http://www.merck.com/product/usa/pi_circulars/g/gardasil_9/gardasil_9_ppi.pdf

.

Merck
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