Lilly’s CYRAMZA (ramucirumab) Becomes First FDA-Approved Treatment for Advanced Gastric Cancer After Prior Chemotherapy

INDIANAPOLIS, May 6, 2014 /PRNewswire/ — Eli Lilly and Company (NYSE: LLY)
announced today that the U.S. Food and Drug Administration (FDA) has approved
CYRAMZA(TM) (ramucirumab) as a single-agent treatment for patients with advanced
or metastatic gastric cancer or gastroesophageal junction (GEJ) adenocarcinoma
with disease progression on or after prior fluoropyrimidine- or
platinum-containing chemotherapy. With this approval, CYRAMZA becomes the first
FDA-approved treatment for patients in this setting.

To view the multimedia assets associated with this release, please click:
http://www.multivu.com/mnr/7139451-lilly-cyramza-fda-approval

“Lilly Oncology is committed to delivering innovative medicines that extend the
lives of people with cancer,” said Richard Gaynor, M.D., senior vice president,
product development and medical affairs for Lilly Oncology. “Until now, there
were no FDA-approved options for patients in this indication. We are pleased
that the FDA has approved CYRAMZA for these patients. This is an aggressive
disease that is difficult to treat, and the prognosis has typically been very
poor.”

The CYRAMZA (ramucirumab injection 10 mg/mL solution) approval is based on
results of REGARD, a multicenter, randomized, placebo-controlled, double-blind
trial of patients with locally advanced or metastatic gastric cancer including
GEJ adenocarcinoma previously treated with fluoropyrimidine- or
platinum-containing chemotherapy. It is the first Phase III trial to show
improved overall survival and progression-free survival with a biologic agent in
advanced gastric cancer after prior chemotherapy. Results demonstrated that
CYRAMZA (8 mg/kg by infusion every two weeks) plus best supportive care (BSC),
as compared to placebo plus BSC, increased the median overall survival of
patients with advanced gastric cancer by 37 percent (median overall survival of
5.2 months [95% confidence interval (CI) 4.4, 5.7] vs. 3.8 months [95% CI 2.8,
4.7] for placebo, P=0.047, hazard ratio 0.78 [95% CI 0.60, 0.998]).
Additionally, CYRAMZA significantly improved progression-free survival,
demonstrating a 62 percent increase in median progression-free survival (2.1
months [95% CI 1.5, 2.7] vs. 1.3 months [95% CI 1.3, 1.4] for placebo, P<0.001,
hazard ratio 0.48 [95% CI 0.38, 0.62]).

The labeling for CYRAMZA contains a Boxed Warning regarding increased risk of
hemorrhage, including severe and sometimes fatal events. CYRAMZA should be
discontinued in patients who experience severe bleeding. The most commonly
reported adverse reactions (all grades) in REGARD, occurring in at least 5
percent of patients receiving CYRAMZA and at a rate at least 2 percent higher
than those receiving placebo, were hypertension (16% vs. 8%), diarrhea (14% vs.
9%), headache (9% vs. 3%), and hyponatremia (6% vs. 2%). The most common serious
adverse events with CYRAMZA were anemia (3.8%) and intestinal obstruction
(2.1%). Red blood cell transfusions were given to 11% of CYRAMZA-treated
patients vs. 8.7% of patients who received placebo. Across clinical trials of
CYRAMZA administered as a single agent, clinically relevant adverse reactions
(including Grade greater than or equal to 3) reported in CYRAMZA-treated
patients included proteinuria, gastrointestinal perforation, and
infusion-related reactions. In REGARD, according to laboratory assessment, 8% of
CYRAMZA-treated patients developed proteinuria versus 3% of placebo-treated
patients. Two patients discontinued CYRAMZA due to proteinuria. The rate of
gastrointestinal perforation in the REGARD trial was 0.8% and the rate of
infusion-related reactions was 0.4%. This is not a complete list of adverse
reactions. For full safety information, see the Important Safety Information at
the end of this press release and the full Prescribing Information.

“There is a high unmet medical need in patients with this disease,” said Charles
Fuchs, M.D., M.P.H., principal investigator of the REGARD trial and director,
Gastrointestinal Malignancy Program, Dana-Farber Cancer Institute. “This
approval represents a meaningful advance for patients and gives those of us who
treat them an important new second-line treatment option.”

“As someone who has experienced firsthand the limited options available to treat
this devastating disease, I consider this approval to be much needed. This is a
significant moment for many patients and their families,” said Debbie Zelman,
president and founder of a leading international patient advocacy organization,
Debbie’s Dream Foundation, which is dedicated to raising awareness about gastric
cancer, advancing funding for research, and providing education and support to
those affected by the disease. Zelman founded the organization following her own
gastric cancer diagnosis. Lilly Oncology and Debbie’s Dream Foundation have
established a partnership to improve patient and caregiver awareness of and
access to gastric cancer resources.

CYRAMZA is a vascular endothelial growth factor (VEGF) Receptor 2 antagonist
that specifically binds VEGF Receptor 2 and blocks binding of VEGF receptor
ligands VEGF-A, VEGF-C, and VEGF-D. VEGF Receptor 2 is an important mediator in
the VEGF pathwayi,ii. In an in vivo animal model, ramucirumab inhibited
angiogenesis. Angiogenesis is a process by which new blood vessels form to
supply blood to normal healthy tissues as well as tumors, enabling the cancer to
grow.

FDA approval of CYRAMZA marks a pivotal regulatory milestone in Lilly’s research
and development program for the molecule, which it acquired when it purchased
ImClone Systems in 2008. CYRAMZA has been granted Orphan Drug Designation by the
FDA for this indication. Orphan drug status is given in the U.S. by the FDA’s
Office of Orphan Products Development (OOPD) to medicines that show promise for
the treatment of rare diseases. Lilly expects to make CYRAMZA available in the
coming weeks and is committed to offering patient assistance programs for
eligible patients receiving CYRAMZA treatment.

Patients, physicians, pharmacists or other healthcare professionals with
additional questions about CYRAMZA should contact The Lilly Answer Center at
1-800-LillyRx or visit www.Lilly.com.

About Angiogenesis
Angiogenesis is the process of making new blood vessels. This process involves
the migration, growth, and differentiation of endothelial cells, which line the
inside wall of blood vessels. Chemical signals in the body stimulate the repair
of damaged blood vessels and formation of new blood vessels during this process.

In a person with cancer, angiogenesis creates new blood vessels that give a
tumor its own blood supply, allowing it to grow and spread.

Some tumors create proteins called VEGF. These proteins attach to the VEGF
receptors of blood vessel cells causing new blood vessels to form around the
tumors, enabling growth. Blocking the VEGF protein from linking to the blood
vessels helps to inhibit tumor growth by slowing angiogenesis and the blood
supply that feeds tumors.

Of the three known VEGF receptors, VEGF Receptor 2 is linked most closely to
VEGF-induced tumor angiogenesis.iii

About CYRAMZA(TM) (ramucirumab)
CYRAMZA (pronounced “si – ram – ze”) as a single agent is the first and only
treatment approved for patients with advanced gastric cancer or gastroesophageal
junction (GEJ) adenocarcinoma who have progressed after prior fluoropyrimidine-
or platinum-containing chemotherapy. CYRAMZA inhibited angiogenesis in an in
vivo animal model. CYRAMZA is a VEGF Receptor 2 antagonist that specifically
binds and blocks activation of VEGF Receptor 2 and blocks binding of VEGF
receptor ligands VEGF-A, VEGF-C, and VEGF-D.

About REGARD
REGARD is a global, randomized, double-blinded, placebo-controlled Phase III
study of CYRAMZA and BSC compared to placebo and BSC as treatment in patients
with locally advanced or metastatic gastric cancer including gastroesophageal
junction adenocarcinoma following progression after initial fluoropyrimidine- or
platinum-containing chemotherapy. In total, 355 patients were randomized in 29
countries. The major efficacy outcome measure (i.e., primary endpoint) of the
REGARD trial was overall survival and the supportive efficacy outcome measure
(i.e., secondary endpoint) was progression-free survival.

About Gastric Cancer
Gastric (stomach) cancer is a major health problem. It is the fifth most common
cancer in the world and is the third-leading cause of cancer death. There were
nearly one million new cases worldwide in 2012 (631,000 men, 320,000 women) with
approximately 723,000 deaths (469,000 men, 254,000 women).iv Stomach cancer is
more prevalent in countries outside the U.S. and EU.v In the U.S., it is
estimated that approximately 22,000 people will be diagnosed with gastric cancer
in 2014.vi

Gastric cancer is a disease in which cancer cells form in the stomach. It
develops slowly, usually over many years, and often goes undetected.vii As
stomach cancer advances, it can travel through the bloodstream and spread to
organs such as the liver, lungs, and bones.viii

The most common type of stomach cancer is called adenocarcinoma, which starts
from one of the common cell types found in the lining of the stomach.ix

Lilly PatientOne
The Lilly PatientOne program addresses financial and coverage issues for
qualified uninsured, underinsured and insured patients who are prescribed a
Lilly Oncology product. Lilly PatientOne provides reimbursement assistance for
eligible patients who are prescribed a Lilly Oncology product, such as
information about coding and billing, prior authorization, benefits
investigation, and denied claim appeals, as well as operating a patient
assistance program. To learn more, visit www.LillyPatientOne.com or call
1-866-4PatOne (1-866-472-8663).

Indication for CYRAMZA
CYRAMZA as a single agent is indicated for the treatment of patients with
advanced or metastatic gastric or gastroesophageal junction adenocarcinoma with
disease progression on or after prior fluoropyrimidine- or platinum-containing
chemotherapy.

IMPORTANT SAFETY INFORMATION FOR CYRAMZA

WARNING: HEMORRHAGE
CYRAMZA increased the risk of
hemorrhage, including severe and
sometimes fatal hemorrhagic
events. Permanently discontinue
CYRAMZA in patients who
experience severe bleeding.
——————————–

Warnings and Precautions
Hemorrhage

— CYRAMZA increased the risk of hemorrhage, including severe and sometimes
fatal hemorrhagic events. In Study 1, which evaluated CYRAMZA as a
single agent in advanced gastric cancer, the incidence of severe
bleeding was 3.4% for CYRAMZA and 2.6% for placebo. Patients with
gastric cancer receiving nonsteroid anti-inflammatory drugs (NSAIDs)
were excluded from enrollment in Study 1; therefore, the risk of gastric
hemorrhage in CYRAMZA-treated patients with gastric tumors receiving
NSAIDs is unknown. Permanently discontinue CYRAMZA in patients who
experience severe bleeding.
Arterial Thromboembolic Events

— Serious, sometimes fatal, arterial thromboembolic events (ATEs)
including myocardial infarction, cardiac arrest, cerebrovascular
accident, and cerebral ischemia occurred in clinical trials including
1.7% of 236 patients who received CYRAMZA as a single agent for gastric
cancer in Study 1. Permanently discontinue CYRAMZA in patients who
experience a severe ATE.
Hypertension

— An increased incidence of severe hypertension occurred in patients
receiving CYRAMZA as a single agent (8%) as compared to placebo (3%).
Control hypertension prior to initiating treatment with CYRAMZA. Monitor
blood pressure every 2 weeks or more frequently as indicated during
treatment. Temporarily suspend CYRAMZA for severe hypertension until
medically controlled. Permanently discontinue CYRAMZA if medically
significant hypertension cannot be controlled with antihypertensive
therapy or in patients with hypertensive crisis or hypertensive
encephalopathy.
Infusion-Related Reactions

— Prior to the institution of premedication recommendations across
clinical trials of CYRAMZA, infusion-related reactions (IRRs) occurred
in 6 out of 37 patients (16%), including 2 severe events. The majority
of IRRs across trials occurred during or following a first or second
CYRAMZA infusion. Symptoms of IRRs included rigors/tremors, back
pain/spasms, chest pain and/or tightness, chills, flushing, dyspnea,
wheezing, hypoxia, and paresthesia. In severe cases, symptoms included
bronchospasm, supraventricular tachycardia, and hypotension. Monitor
patients during the infusion for signs and symptoms of IRRs in a setting
with available resuscitation equipment. Immediately and permanently
discontinue CYRAMZA for Grade 3 or 4 IRRs.
Gastrointestinal Perforations

— CYRAMZA is an antiangiogenic therapy that can increase the risk of
gastrointestinal perforation, a potentially fatal event. Four of 570
patients (0.7%) who received CYRAMZA as a single agent in clinical
trials experienced gastrointestinal perforation. Permanently discontinue
CYRAMZA in patients who experience a gastrointestinal perforation.
Impaired Wound Healing

— CYRAMZA has not been studied in patients with serious or nonhealing
wounds. CYRAMZA is an antiangiogenic therapy with the potential to
adversely affect wound healing. Withhold CYRAMZA prior to surgery.
Resume CYRAMZA following the surgical intervention based on clinical
judgment of adequate wound healing. If a patient develops wound healing
complications during therapy, discontinue CYRAMZA until the wound is
fully healed.
Clinical Deterioration in Child-Pugh B or C Cirrhosis

— Clinical deterioration, manifested by new onset or worsening
encephalopathy, ascites, or hepatorenal syndrome, was reported in
patients with Child-Pugh B or C cirrhosis who received single-agent
CYRAMZA. Use CYRAMZA in patients with Child-Pugh B or C cirrhosis only
if the potential benefits of treatment are judged to outweigh the risks
of clinical deterioration.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS)

— RPLS has been reported at a rate of <0.1% in clinical studies with
CYRAMZA. Confirm the diagnosis of RPLS with MRI and discontinue CYRAMZA
in patients who develop RPLS. Symptoms may resolve or improve within
days, although some patients with RPLS can experience ongoing neurologic
sequelae or death.
Most Common Adverse Reactions

— The most commonly reported adverse reactions (all grades) occurring in
>=5% of patients receiving CYRAMZA and >=2% higher than placebo in Study
1 were hypertension (16% vs 8%), diarrhea (14% vs 9%), headache (9% vs
3%), and hyponatremia (6% vs 2%).
— The most common serious adverse events with CYRAMZA in Study 1 were
anemia (3.8%) and intestinal obstruction (2.1%). Red blood cell
transfusions were given to 11% of CYRAMZA-treated patients vs 8.7% of
patients who received placebo.
— Clinically relevant adverse reactions reported in >=1% and <5% of
CYRAMZA-treated patients in Study 1 were: neutropenia (4.7% vs 0.9%),
epistaxis (4.7% vs 0.9%), rash (4.2% vs 1.7%), intestinal obstruction
(2.1% vs 0%), and arterial thromboembolic events (1.7% vs 0%).
— Across clinical trials of CYRAMZA administered as a single agent,
clinically relevant adverse reactions (including Grade >=3) reported in
CYRAMZA-treated patients included proteinuria, gastrointestinal
perforation, and infusion-related reactions. In Study 1, according to
laboratory assessment, 8% of CYRAMZA-treated patients developed
proteinuria vs 3% of placebo-treated patients. Two patients discontinued
CYRAMZA due to proteinuria. The rate of gastrointestinal perforation in
Study 1 was 0.8% and the rate of infusion-related reactions was 0.4%.
— As with all therapeutic proteins, there is the potential for
immunogenicity. In clinical trials, 33/443 (7.4%) CYRAMZA-treated
patients with post-baseline serum samples tested positive for
anti-ramucirumab antibodies using an enzyme-linked immunosorbent assay
(ELISA). However, this assay has limitations in detecting
anti-ramucirumab antibodies in the presence of ramucirumab; therefore,
the incidence of antibody development may not have been reliably
determined. Neutralizing antibodies were detected in 1 of the 33
patients who tested positive for anti-ramucirumab antibodies.
Drug Interactions

— No formal drug interaction studies have been conducted.
Use in Specific Populations

— Pregnancy Category C: Based on its mechanism of action, CYRAMZA may
cause fetal harm. Advise females of reproductive potential to avoid
getting pregnant, including use of adequate contraception, while
receiving CYRAMZA and for at least 3 months after the last dose of
CYRAMZA. Animal models link angiogenesis, VEGF and VEGF Receptor 2 to
critical aspects of female reproduction, embryofetal development, and
postnatal development. There are no adequate or well-controlled studies
of ramucirumab in pregnant women. If this drug is used during pregnancy,
or if the patient becomes pregnant while taking this drug, apprise the
patient of the potential hazard to a fetus.
— Nursing Mothers: It is recommended to discontinue nursing or discontinue
CYRAMZA due to the potential risks to the nursing infant.
— Females of Reproductive Potential: Advise females of reproductive
potential that CYRAMZA may impair fertility.
Please see full Prescribing Information for CYRAMZA, including Boxed Warning for
hemorrhage at http://pi.lilly.com/us/cyramza-pi.pdf.

RB HCP ISI 21APR2014

About Lilly Oncology
For more than fifty years, Lilly has been dedicated to delivering life-changing
medicines and support to people living with cancer and those who care for them.
Lilly is determined to build on this heritage and continue making life better
for all those affected by cancer around the world. To learn more about Lilly’s
commitment to people with cancer, please visit www.LillyOncology.com.

About Eli Lilly and Company
Lilly is a global healthcare leader that unites caring with discovery to make
life better for people around the world. We were founded more than a century ago
by a man committed to creating high-quality medicines that meet real needs, and
today we remain true to that mission in all our work. Across the globe, Lilly
employees work to discover and bring life-changing medicines to those who need
them, improve the understanding and management of disease, and give back to
communities through philanthropy and volunteerism. To learn more about Lilly,
please visit us at www.lilly.com and http://newsroom.lilly.com/social-channels.

RB88157 <04/2014> © Lilly USA, LLC 2014. ALL RIGHTS RESERVED.

CYRAMZA(TM) is a trademark of Eli Lilly and Company.

P-LLY

This press release contains forward-looking statements about the potential of
CYRAMZA (ramucirumab) as a treatment of advanced stomach cancer or
gastroesophageal junction (GEJ) adenocarcinoma and reflects Lilly’s current
beliefs. However, as with any pharmaceutical product, there are substantial
risks and uncertainties in the process of development and commercialization.
There can be no guarantee that future study results and patient experience will
be consistent with the study findings to date. There can also be no guarantee
that CYRAMZA will receive regulatory approval for any future indications or that
it will prove to be commercially successful. For further discussion of these and
other risks and uncertainties that could cause actual results to differ from
Lilly’s expectations, please see the company’s latest Forms 10-K and 10-Q filed
with the U.S. Securities and Exchange Commission. Except as required by law,
Lilly undertakes no duty to update forward-looking statements.

i Shibuya M. Vascular endothelial growth factor-dependent and -independent
regulation of angiogenesis. BMB Rep. 2008;41(4):278-286.

iiSpratlin J. Ramucirumab (IMC-1121B): monoclonal antibody inhibition of
vascular endothelial growth factor receptor-2. Curr Oncol Rep. 2011;13
(2):97-102.

iiiSpratlin J. Ramucirumab (IMC-1121B): monoclonal antibody inhibition of
vascular endothelial growth factor receptor-2. Curr Oncol Rep. 2011;13
(2):97-102.

iv Globocan 2012 Cancer Fact Sheet. Stomach cancer estimated incidence,
mortality and prevalence worldwide in 2012.
http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx. Accessed January 21,
2014.

v Globocan 2012 Cancer Fact Sheet. Stomach cancer estimated incidence, mortality
and prevalence worldwide in 2012.
http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx. Accessed January 21, 2014

vi American Cancer Society. What are the key statistics about stomach cancer?
http://www.cancer.org/Cancer/StomachCancer/DetailedGuide/stomach-cancer-key-statistics.
Updated February 22, 2013. Accessed September 25, 2013.

vii American Cancer Society. What is stomach cancer?
http://www.cancer.org/Cancer/StomachCancer/index. Updated February 22, 2013.
Accessed January 21, 2014.

viiiAmerican Cancer Society. What is stomach cancer?
http://www.cancer.org/Cancer/StomachCancer/index. Updated February 22, 2013.
Accessed January 21, 2014.

ix National Center for Biotechnology Information. Gastric cancer.
http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001270/. Updated November 17, 2012.
Accessed January 21, 2014.

Contact: Tracy Henrikson (Lilly Oncology) Mary Coyle (TogoRun)

609-240-3902 (mobile) 212-453-2089 (office)

Email: tracy.henrikson@imclone.com 917-975-6615 (mobile)

Email: m.coyle@togorun.com

Keri McGrath (Lilly Oncology)

317-370-8394 (mobile)

Email: mcgrath_happe_keri_s@lilly.com

SOURCE Eli Lilly and Company

Leave a Reply


Fatal error: Call to undefined function show_subscription_checkbox() in /home3/steer/public_html/indianapressreleases.com/wp-content/themes/comfy/comments.php on line 95