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October 14, 2013 4:02 pm ET

Merck and Endocyte’s Phase III PROCEED pivotal trial of vintafolide in ovarian cancer ongoing

Merck, known as MSD outside the United States and Canada, (NYSE: MRK)
and Endocyte, Inc. (NASDAQ: ECYT) today announced the online publication
of results from the randomized Phase II PRECEDENT trial for vintafolide
(MK-8109/EC145), an investigational folate small molecule drug conjugate
(SMDC), in the Journal of Clinical Oncology (JCO), the official
journal of the American Society of Clinical Oncology. These trial
results are the basis for the vintafolide regulatory application
currently under review with the European Medicines Agency for the
treatment of folate-receptor positive platinum-resistant ovarian cancer
in combination with pegylated liposomal doxorubicin (PLD). Enrollment is
ongoing in the pivotal Phase III PROCEED clinical trial with
vintafolide, along with investigational companion imaging agent
etarfolatide (EC20), in platinum-resistant ovarian cancer
(Clinicaltrials.gov NCT01170650).

As reported in JCO online, results from the Phase II PRECEDENT
trial showed that administration of vintafolide plus pegylated liposomal
doxorubicin (PLD) versus PLD alone in women with platinum-resistant
ovarian cancer resulted in a median progression-free survival (PFS) of
5.0 months compared to 2.7 months for those treated with PLD alone
(HR=0.63; 95% CI 0.41–0.96; p=0.031) in the intent-to-treat (ITT)
population. Those patients shown to have folate receptor-positive
tumors, as defined by all selected target lesions being folate
receptor-positive (FR%100) using the investigational folate
receptor-targeted companion diagnostic imaging agent etarfolatide,
demonstrated greater benefit, as measured by PFS, from treatment with
vintafolide plus PLD versus PLD alone. Median PFS benefit in these
patients was 5.5 months compared to 1.5 months for PLD alone (HR=0.38;
95% CI 0.17–0.85; p=0.013). Etarfolatide is being developed by Endocyte
as a non-invasive method to identify tumors that express the folate
receptor.

“The combination of vintafolide plus PLD demonstrated significant
improvement in progression-free survival over standard treatment in
women with folate receptor-positive platinum-resistant ovarian cancer,”
said R. Wendel Naumann, M.D., Associate Director, Gynecologic Oncology,
Carolinas HealthCare System’s Levine Cancer Institute, Charlotte, N.C.,
and corresponding author of the publication. “Targeting the folate
receptor, which is expressed on the majority of epithelial ovarian
cancers, is a potentially promising strategy, especially when combined
with a companion diagnostic that is designed to identify patients who
are most likely to respond to the treatment, a hallmark of personalized
medicine.”

The Phase II PRECEDENT trial was an international, multi-center,
randomized study of 149 women with platinum-resistant ovarian cancer.
Patients were randomized to receive vintafolide plus PLD or PLD
alone at a standard dose, until disease progression or death. The
primary endpoint of the study was PFS. Secondary endpoints included
response rate and overall survival (OS). In the ITT population, no
difference was observed in overall survival (HR=1.010; 95% CI
0.679–1.503; p=0.957). Endocyte first presented results from the Phase
II PRECEDENT trial at the 2011 American Society of Clinical Oncology
Annual Meeting.

The combination of vintafolide and PLD was generally well tolerated, and
no drug-related mortality or statistically significant difference in the
incidence of drug-related serious treatment-emergent adverse events
(TEAEs) was observed.

• In the vintafolide and PLD arm vs. PLD arm, anemia, neutropenia and
  thrombocytopenia were reported in 16.6% vs. 10.4%, 19.1% vs. 10.4%,
  and 2.7% vs. 3.0% of all cycles, respectively.
• Stomatitis and palmar-plantar erythrodysesthesia (hand-foot syndrome)
  occurred in 16.6% vs. 22.8%, and 19.1% vs.15.8% of cycles,
  respectively.
• The frequency of fatigue was similar between arms, 15.8% of
  vintafolide and PLD arm cycles, and 14.9% of PLD arm cycles.

About Folate Receptor-Positive Platinum-Resistant Ovarian Cancer

In 2013, it is estimated that there will be 22,240 new cases of ovarian
cancer in the United States and over 40,000 new cases in the European
Union. Ovarian cancer is one of the most lethal cancers of the female
reproductive system. Overall, approximately 80 percent of patients
relapse after first-line platinum-based chemotherapy. Platinum-resistant
ovarian cancer is a challenging disease with a high unmet need. This
type of cancer recurs within six months of completion with a
platinum-containing regimen, the standard of care for ovarian cancer.
Based on the Phase II PRECEDENT trial data, an estimated 80 percent of
platinum-resistant ovarian cancer patients have been found to have
folate receptor-positive disease as assessed by etarfolatide scanning,
and approximately 40 percent express the receptor, as detected by
etarfolatide, in all of their target tumor lesions.

About Vintafolide (MK-8109/EC145)

Vintafolide is an investigational proprietary, injectable, folate SMDC
consisting of folate (vitamin B9) linked to a potent vinca alkaloid
chemotherapy agent, desacetylvinblastine hydrazide (DAVLBH). Vintafolide
is designed to target the chemotherapy agent to rapidly growing cancer
cells that actively take up folate via the folate receptor. The folate
receptor is expressed in a wide variety of cancers including ovarian
cancer.

Vintafolide (MK-8109/EC145) in combination with PLD is currently under
review with European Medicines Agency (EMA) for the treatment of adult
patients with folate receptor-positive platinum-resistant ovarian
cancer. Vintafolide has also been granted orphan drug status by the
European Commission. Vintafolide, along with investigational companion
imaging agent etarfolatide, is currently being evaluated in a Phase III
PROCEED clinical trial for platinum-resistant ovarian cancer,
(Clinicaltrials.gov NCT01170650)
and a Phase IIb TARGET trial for non-small cell lung cancer (NSCLC)
(Clinicaltrials.gov NCT01577654).
A Phase II randomized trial of vintafolide in folate receptor-positive
triple negative breast cancer is expected to be initiated in the near
future.

As part of an exclusive license agreement with Endocyte, Merck is
responsible for the development and worldwide commercialization of
vintafolide. Endocyte would intend to co-promote vintafolide in the U.S.
pending regulatory filing and approval, and is responsible for the
development, manufacture and commercialization of etarfolatide worldwide.

About Etarfolatide (EC20)

Etarfolatide is an investigational folate receptor-targeted companion
diagnostic imaging agent that is being developed as a non-invasive
method to identify tumors that express the folate receptor. These tumors
are the molecular target of Endocyte’s folate receptor-targeted
therapeutic compounds such as vintafolide. Folic acid is used with
etarfolatide for the enhancement of image quality. Etarfolatide is under
review with the EMA and has been granted orphan drug status by the
European Commission.

About Merck

Today’s Merck is a global healthcare leader working to help the world be
well. Merck is known as MSD outside the United States and Canada.
Through our prescription medicines, vaccines, biologic therapies, and
consumer care 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
healthcare through far-reaching policies, programs and partnerships. For
more information, visit www.merck.com
and connect with us on Twitter,
Facebook
and YouTube.

About Endocyte

Endocyte is a biopharmaceutical company developing targeted therapies
for the treatment of cancer and other serious diseases. Endocyte uses
its proprietary technology to create novel SMDCs and companion imaging
diagnostics for personalized targeted therapies. The company’s SMDCs
actively target receptors that are expressed on diseased cells, relative
to healthy cells. This targeted approach is designed to enable the
treatment of patients with highly active drugs at greater doses,
delivered more frequently and over longer periods of time than would be
possible with the untargeted drug alone. The companion imaging
diagnostics are designed to identify patients whose disease expresses
the molecular target of the therapy and who are therefore more likely to
benefit from treatment. Targeted SMDCs for cancer, inflammatory
disorders and kidney disease are in preclinical development. For
additional information, please visit Endocyte’s website at www.endocyte.com.

Merck Forward-Looking Statement

This news release includes “forward-looking statements” within the
meaning of the safe harbor provisions of the United States Private
Securities Litigation Reform Act of 1995. These statements are based
upon the current beliefs and expectations of Merck’s management and are
subject to significant risks and uncertainties. There can be no
guarantees with respect to pipeline products that the products will
receive the necessary regulatory approvals or that they will prove to be
commercially successful. 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; Merck’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 Merck’s patents and other protections
for innovative products; and the exposure to litigation, including
patent litigation, and/or regulatory actions.

Merck 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 Merck’s 2012 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).

Endocyte Forward-Looking Statement

Certain of the statements in this press release are forward looking,
such as those, among others, relating to the potential effectiveness of
folate receptor-targeted therapies, the ability to determine the folate
receptor expression status of patients, and the timing of clinical trial
enrollment. Actual results or developments may differ materially from
those projected or implied in these forward-looking statements. More
information about the risks and uncertainties faced by Endocyte, Inc. is
contained in the company’s periodic reports filed with the Securities
and Exchange Commission. Endocyte, Inc. disclaims any intention or
obligation to update or revise any forward-looking statements, whether
as a result of new information, future events or otherwise.

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Merck
Media:
Caroline Lappetito,267-305-7639
Caroline.Lappetito@Merck.com
or
Claire Mulhearn, 908-423-7425
Claire.Mulhearn@Merck.com
or
Investors:
Carol Ferguson, 908-423-4465
Carol.Ferguson@Merck.com
or
Justin Holko, 908-423-5088
Justin_Holko@Merck.com
or
Endocyte
Media:
Tony Russo, 212-845-4251
Tony.Russo@Russopartnersllc.com
or
Martina Schwarzkopf, 212-845-4292
Martina.Schwarzkopf@Russopartnersllc.com
or
Investors:
Stephanie Ascher, 212-362-1200
Stephanie@sternir.com