Pfizer Receives FDA Approval for MYLOTARG™ (gemtuzumab ozogamicin)

NEW YORK–(BUSINESS WIRE)– Pfizer Inc. (NYSE:PFE) today announced that the U.S. Food and Drug
Administration approved MYLOTARG™ (gemtuzumab ozogamicin) for adults
with newly diagnosed CD33-positive acute myeloid leukemia (AML), and
adults and children 2 years and older with relapsed or refractory
CD33-positive AML.¹ MYLOTARG is the first therapy with an
indication that includes pediatric AML. It is also the only AML therapy
that targets CD33, an antigen expressed on AML cells in up to 90% of
patients.

“The FDA approval of MYLOTARG fills a critical unmet need for many
adults and children with AML, which can be fatal in a matter of months
or even weeks if not treated and has a high relapse rate,” said Liz
Barrett, global president, Pfizer Oncology. “Based on clinical data,
real-world experience and support from the AML community, we are
grateful MYLOTARG now has the potential to help a broad range of AML
patients.”

MYLOTARG was originally approved in 2000 at a higher dose under the
FDA’s accelerated approval program for use as a single agent in patients
with CD33-positive AML who had experienced their first relapse and were
60 years or older and who were not considered candidates for other
cytotoxic chemotherapy. In 2010, Pfizer voluntarily withdrew MYLOTARG in
the U.S. after a confirmatory trial failed to show clinical benefit and
there was a higher rate of fatal toxicity compared to chemotherapy.
MYLOTARG has remained on the market in Japan and has been available to
individual patients through Pfizer’s compassionate use programs. Due to
the critical unmet need for patients with AML, there remained great
interest among AML clinicians to evaluate MYLOTARG using different doses
and different schedules. These independent investigators, with Pfizer’s
support, conducted clinical trials that yielded more information on the
efficacy and safety of MYLOTARG.

“Today is an important day for patients, their families and the entire
AML community, as the approval of MYLOTARG brings forth a long-awaited
treatment option that may lead to deeper, more durable remissions for
patients with AML,” said Jorge Cortes, MD, University of Texas, MD
Anderson Cancer Center. “After many years, we are finally seeing
progress in the treatment of AML, which has renewed my hope in improving
outcomes for my patients. I am pleased that I can now offer many adult
and pediatric patients targeted treatment with MYLOTARG.”

Today’s approval of MYLOTARG is based on several investigator-led
clinical trials, including ALFA-0701, AML-19 and MyloFrance-1.¹

The ALFA-0701 trial was a Phase 3, multicenter, randomized, open-label
study of 271 patients with newly-diagnosed de novo AML, using a new,
lower fractionated dose of MYLOTARG. Patients received MYLOTARG 3 mg/m²
on days 1, 4 and 7 in combination with conventional chemotherapy or
chemotherapy alone. The primary endpoint was event-free survival (EFS).
Administering MYLOTARG (n=135) in addition to standard induction
chemotherapy resulted in a significant improvement in EFS compared with
chemotherapy alone (n=136) in patients with newly diagnosed AML.
Event-free survival was 17.3 months for patients receiving MYLOTARG
compared with 9.5 months for those receiving chemotherapy alone (HR =
0.56 [95% CI: (0.42, 0.76)]).¹

Study AML-19 was a multicenter, randomized, open-label Phase 3 study
comparing single agent MYLOTARG (n=118) to best supportive care (n=119)
for elderly patients who could not tolerate other AML therapies. As
initial treatment, patients received MYLOTARG 6 mg/m² on day
1 and MYLOTARG 3 mg/m² on day 8. As continued treatment,
patients without evidence of disease progression received MYLOTARG 2 mg/m²
on day 1 every 4 weeks. The efficacy of MYLOTARG was established on the
basis of a significant improvement in overall survival (OS). Median OS
was 4.9 months for patients receiving MYLOTARG compared with 3.6 months
for patients receiving best supportive care (HR=0.69 [95% CI: 0.53-0.90] [2-sided p=0.005]).¹

MyloFrance-1 was a Phase 2, single-arm, open-label study of 57 adult
patients in first relapse. Patients received single agent MYLOTARG 3mg/m²
on days 1, 4 and 7. The efficacy of MYLOTARG was established on the
basis of complete remission (CR) rate and duration of remission. In the
trial, 15 (26%; 95% CI: 16%-40%) patients achieved a complete remission
(CR) and median relapse-free survival (RFS) was 11.6 months.¹

The U.S. labeling for MYLOTARG includes a boxed warning for
hepatotoxicity, including severe or fatal hepatic veno-occlusive disease
(VOD). Veno-occlusive disease has been reported in association with the
use of MYLOTARG as a single agent and as part of a combination
chemotherapy regimen (5%). In patients who received MYLOTARG, the most
common (≥15%) adverse reactions were hemorrhage, infection, fever,
nausea, vomiting, constipation, headache, increased ALT, increased AST,
rash and mucositis.

Pfizer is committed to helping patients gain access to Pfizer medicines,
including MYLOTARG, and related educational tools, resources and
services, regardless of their financial or health insurance status
through the company’s patient assistance programs. Patients can visit www.MYLOTARG.com
or call 1-877-744-5675 to learn more.

The full prescribing information, including BOXED WARNING, for MYLOTARG
can be found here: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761060lbl.pdf

IMPORTANT MYLOTARG™ (gemtuzumab ozogamicin) SAFETY INFORMATION FROM
THE U.S. PRESCRIBING INFORMATION

WARNING: Hepatotoxicity, including severe or fatal hepatic
veno-occlusive disease (VOD), also known as sinusoidal obstruction
syndrome (SOS), has been reported in association with the use of
MYLOTARG as a single agent, and as part of a combination chemotherapy
regimen. Monitor frequently for signs and symptoms of VOD after
treatment with MYLOTARG.

Hepatotoxicity, Including Veno-occlusive Liver Disease (VOD): An
increased risk of VOD was observed in patients with moderate/severe
hepatic impairment and patients who received MYLOTARG either before or
after HSCT. Assess ALT, AST, total bilirubin, and alkaline phosphatase
prior to each dose of MYLOTARG. After treatment with MYLOTARG, monitor
frequently for signs and symptoms of VOD; these may include elevations
in ALT, AST, and total bilirubin, hepatomegaly, rapid weight gain, and
ascites. Monitoring only total bilirubin may not identify all patients
at risk of VOD. For patients who develop abnormal liver tests, more
frequent monitoring of liver tests and clinical signs and symptoms of
hepatotoxicity is recommended. For patients who proceed to HSCT, monitor
liver tests frequently during the post-HSCT period, as appropriate.
Manage signs or symptoms of hepatic toxicity by dose interruption or
discontinuation of MYLOTARG. In patients who experience VOD, discontinue
MYLOTARG and treat according to standard medical practice.

Infusion-Related Reactions (Including Anaphylaxis):
Life-threatening or fatal infusion-related reactions can occur during or
within 24 hours following infusion of MYLOTARG. Signs and symptoms of
infusion-related reactions may include fever, chills, hypotension,
tachycardia, hypoxia, and respiratory failure. Premedicate prior to
MYLOTARG infusion. Monitor vital signs frequently during infusion.
Interrupt infusion immediately for patients who develop evidence of
infusion reaction, especially dyspnea, bronchospasm, or hypotension.
Monitor patients during and for at least 1 hour after the end of the
infusion or until signs and symptoms completely resolve. Discontinue use
of MYLOTARG in patients who develop signs or symptoms of anaphylaxis,
including severe respiratory symptoms or clinically significant
hypotension.

Hemorrhage: MYLOTARG is myelosuppressive and can cause fatal or
life-threatening hemorrhage due to prolonged thrombocytopenia. Assess
blood counts prior to each dose of MYLOTARG and monitor blood counts
frequently after treatment with MYLOTARG until resolution of cytopenias.
Monitor patients for signs and symptoms of bleeding during treatment
with MYLOTARG. Manage severe bleeding, hemorrhage, or persistent
thrombocytopenia using dose delay or permanent discontinuation of
MYLOTARG, and provide supportive care per standard practice.

QT Interval Prolongation: QT interval prolongation has been
observed in patients treated with other drugs containing calicheamicin.
When administering MYLOTARG to patients who have a history of or
predisposition for QTc prolongation, who are taking medicinal products
that are known to prolong QT interval, and in patients with electrolyte
disturbances, obtain electrocardiograms and electrolytes prior to the
start of treatment and as needed during administration.

Adverse Cytogenetics: In a subgroup analysis in ALFA-0701,
the addition of MYLOTARG to standard combination chemotherapy did not
improve event-free survival in the subgroup of patients having
adverse-risk cytogenetics. For patients being treated with MYLOTARG in
combination with daunorubicin and cytarabine for newly diagnosed de novo
AML, when cytogenetics testing results become available consider whether
the potential benefit of continuing treatment with MYLOTARG outweighs
the risks for the individual patient.

Embryo-Fetal Toxicity: MYLOTARG can cause embryo-fetal harm when
administered to a pregnant woman. Advise patients of reproductive
potential to use effective contraception during and for 3 and 6 months
following treatment for males and females, respectively. Apprise
pregnant women of the potential risk to the fetus. Advise women to
contact their healthcare provider if they become pregnant or if
pregnancy is suspected during treatment with MYLOTARG.

Adverse Reactions: The most common adverse reactions (greater
than 15%) were hemorrhage, infection, fever, nausea, vomiting,
constipation, headache, increased AST, increased ALT, rash, and
mucositis.

Contraindications: Hypersensitivity to MYLOTARG or any of its
components. Reactions have included anaphylaxis.

The full prescribing information, including BOXED WARNING, for MYLOTARG
can be found here: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761060lbl.pdf.

About AML

Acute myeloid leukemia (AML) is the most common type of acute leukemia
in adults and accounts for approximately 80% of all cases of acute
leukemia.² About 21,380 people are expected to be diagnosed
with AML in the United States in 2017.³ The majority of AML
cases occur in adults, but about 500 children are diagnosed with AML
each year.⁴ Acute myeloid leukemia is the second most common
leukemia in children.⁶ The majority of children (85%) will
achieve a response after initial treatment, with approximately 5% being
refractory to treatment.⁵ Additionally, approximately 30% of
children will have their disease return⁵. Only one in four
patients with AML survive longer than five years.⁴

About MYLOTARG™ (gemtuzumab ozogamicin)

MYLOTARG is an antibody-drug conjugate (ADC) composed of the cytotoxic
agent calicheamicin, attached to a monoclonal antibody (mAB) targeting
CD33, an antigen expressed on the surface of myeloblasts in up to 90
percent of AML patients.^6,7,8 When MYLOTARG binds to the CD33
antigen on the cell surface it is absorbed into the cell and
calicheamicin is released causing cell death.^1,7,8

MYLOTARG is commercially available in Japan where it is approved for the
treatment of patients with relapsed or refractory CD33-positive AML who
are not considered candidates for other cytotoxic chemotherapy.

MYLOTARG originates from a collaboration between Pfizer and Celltech,
now UCB. Pfizer has sole responsibility for all manufacturing, clinical
development and commercialization activities for this molecule.

About Pfizer Oncology

Pfizer Oncology is committed to pursuing innovative treatments that have
a meaningful impact on those living with cancer. As a leader in oncology
speeding cures and accessible breakthrough medicines to patients, Pfizer
Oncology is helping to redefine life with cancer. Our strong pipeline of
biologics, small molecules and immunotherapies, one of the most robust
in the industry, is studied with precise focus on identifying and
translating the best scientific breakthroughs into clinical application
for patients across a wide range of cancers. By working collaboratively
with academic institutions, individual researchers, cooperative research
groups, governments and licensing partners, Pfizer Oncology strives to
cure or control cancer with its breakthrough medicines. Because Pfizer
Oncology knows that success in oncology is not measured solely by the
medicines you manufacture, but rather by the meaningful partnerships you
make to have a more positive impact on people’s lives.

Pfizer Inc.: Working together for a healthier world^TM

At Pfizer, we apply science and our global resources to bring therapies
to people that extend and significantly improve their lives. We strive
to set the standard for quality, safety and value in the discovery,
development and manufacture of health care products. Our global
portfolio includes medicines and vaccines as well as many of the world’s
best-known consumer health care products. Every day, Pfizer colleagues
work across developed and emerging markets to advance wellness,
prevention, treatments and cures that challenge the most feared diseases
of our time. Consistent with our responsibility as one of the world’s
premier innovative biopharmaceutical companies, we collaborate with
health care providers, governments and local communities to support and
expand access to reliable, affordable health care around the world. For
more than 150 years, we have worked to make a difference for all who
rely on us. We routinely post information that may be important to
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In addition, to learn more, please visit us on www.pfizer.com
and follow us on Twitter at @Pfizer
and @Pfizer_News,
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and like us on Facebook at Facebook.com/Pfizer.

DISCLOSURE NOTICE: The information contained in this release is as of
September 1, 2017. Pfizer assumes no obligation to update
forward-looking statements contained in this release as the result of
new information or future events or developments.

This release contains forward-looking information about MYLOTARG
(gemtuzumab ozogamicin), an antibody-drug conjugate, including its
potential benefits, that involves substantial risks and uncertainties
that could cause actual results to differ materially from those
expressed or implied by such statements. Risks and uncertainties
include, among other things, the uncertainties inherent in research and
development, including the ability to meet anticipated clinical trial
commencement and completion dates and regulatory submission dates, as
well as the possibility of unfavorable clinical trial results, including
unfavorable new clinical data and additional analyses of existing
clinical data; whether and when applications for MYLOTARG may be filed
in any other jurisdictions; whether and when any such applications for
MYLOTARG that maybe be pending or filed may be approved by regulatory
authorities, which will depend on the assessment by such regulatory
authorities of the benefit-risk profile suggested by the totality of the
efficacy and safety information submitted; decisions by regulatory
authorities regarding labeling and other matters that could affect the
availability or commercial potential of MYLOTARG; and competitive
developments.

A further description of risks and uncertainties can be found in
Pfizer’s Annual Report on Form 10-K for the fiscal year ended December
31, 2016 and in its subsequent reports on Form 10-Q, including in the
sections thereof captioned “Risk Factors” and “Forward-Looking
Information and Factors That May Affect Future Results”, as well as in
its subsequent reports on Form 8-K, all of which are filed with the U.S.
Securities and Exchange Commission and available at www.sec.gov
and www.pfizer.com.

¹ MYLOTARG (gemtuzumab ozogamicin) Prescribing Information.
New York. NY: Pfizer Inc: 2017.
² Leukemia & Lymphoma
Society, Acute Myeloid Leukemia Booklet. Developed 2011. Accessed July
2017. https://www.lls.org/sites/default/files/file_assets/aml.pdf
³
National Cancer Institute. SEER Cancer Stat Facts: Acute Myeloid
Leukemia. National Cancer Institute. Bethesda, MD, April 2017. Available
at: http://seer.cancer.gov/statfacts/html/amyl.html.
Accessed July 2017.
⁴ American Society of Clinical
Oncology. Leukemia – Acute Myeloid – AML – Childhood: Statistics.
Available at: http://www.cancer.net/cancer-types/leukemia-acute-myeloid-aml-childhood/statistics.
Accessed August 2017.
⁵ Creutzig U, van den
Heuvel-Eibrink MM, Gibson B, et al: Diagnosis and management of acute
myeloid leukemia in children and adolescents: recommendations from an
international expert panel. Blood 2012 120:3187-3205.
⁶
Griffin JD, Linch D, Sabbath K, et al: A monoclonal antibody reactive
with normal and leukemic human myeloid progenitor cells. Leuk Res 8:
521-534, 1984 CrossRefMedline.
⁷ Tanaka M, Kano Y, et
al. The Cytotoxic Effects of Gemtuzumab Ozogamicin (Mylotarg) in
Combination with Conventional Antileukemic Agents by Isobologram
Analysis In Vitro. Anticancer Research. 2009; 29: 4589-4596.
⁸
O’Hear C, Heiber JF, Schubert I, Fey G, Geiger TL. Anti-CD33 chimeric
antigen receptor targeting of acute myeloid leukemia. Haematologica.
2015;100(3):336-344.

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