Pfizer Receives U.S. FDA Approval for BESPONSA® (inotuzumab ozogamicin)

BESPONSA is the first and only CD22-directed antibody-drug conjugate
indicated for the treatment of adults with relapsed or refractory B-cell
precursor acute lymphoblastic leukemia

NEW YORK–(BUSINESS WIRE)–Pfizer Inc. (NYSE:PFE) today announced that the U.S. Food and Drug
Administration (FDA) has approved BESPONSA® (inotuzumab ozogamicin) for
the treatment of adults with relapsed or refractory B-cell precursor
acute lymphoblastic leukemia (ALL).1 BESPONSA was reviewed
and approved under the FDA’s Breakthrough Therapy designation and
Priority Review programs.

“The approval of BESPONSA is an important step forward for adult
patients with relapsed or refractory B-cell acute lymphoblastic
leukemia, a rare disease that can be fatal within a matter of months if
left untreated,” said Liz Barrett, global president, Pfizer Oncology.
“BESPONSA will help address a significant need for new treatment options
in B-cell acute lymphoblastic leukemia, and may help more patients reach
stem cell transplant, which provides the best chance for long term
remission. We’re proud to build on our continued commitment to patients
with hematologic malignancies, and will continue our work to find new
treatments in acute lymphoblastic leukemia and other blood cancers.”

The approval was based on results from the Phase 3 INO-VATE ALL trial, a
randomized, open-label, international, multicenter study evaluating the
safety and efficacy of BESPONSA compared with Investigator’s choice of
chemotherapy in 326 adult patients with relapsed or refractory B-cell

“Based on the results seen in the INO-VATE ALL trial, BESPONSA improved
multiple efficacy measures, including rates of hematologic remission,
MRD-negativity and stem cell transplantation,” said Hagop M. Kantarjian,
M. D., INO-VATE ALL lead study investigator and professor, The
University of Texas MD Anderson Cancer Center. “I look forward to seeing
the impact this important new therapy may have on my patients.”

The complete remission rate (CR/CRi)* for patients treated with BESPONSA
was 81 percent [95% CI: 72%-88%] compared to 29 percent with
chemotherapy [95% CI: 21%-39%]. Among patients achieving CR/CRi, those
treated with BESPONSA also demonstrated a higher rate of minimal
residual disease (MRD) negativity (78% [95% CI: 68%-87%]) compared to
those treated with chemotherapy (28% [95% CI: 14%-47%]). Forty-eight
percent of patients treated with BESPONSA proceeded to hematopoietic
stem cell transplantation (HSCT) compared to 22 percent treated with
chemotherapy. The median overall survival (OS) for patients treated with
BESPONSA was 7.7 months [95% CI: 6.0, 9.2] and 6.2 months [95% CI: 4.7,
8.3] for patients treated with chemotherapy. The analysis of OS for
patients treated with BESPONSA compared to chemotherapy did not meet the
pre-specified boundary for statistical significance (HR: 0.75 [97.5% CI:

The U.S. labeling for BESPONSA includes a boxed warning for
hepatotoxicity, including hepatic veno-occlusive disease (VOD), also
known as sinusoidal obstruction syndrome (SOS), and increased risk of
post-HSCT non-relapse mortality. Veno-occlusive disease, including fatal
and life-threating VOD, occurred in 14 percent of patients treated with
BESPONSA. A higher post-HSCT non-relapse mortality rate occurred in
patients treated with BESPONSA (39%) than chemotherapy (23%).1
In patients treated with BESPONSA, the most common (≥20%) adverse
reactions were thrombocytopenia, neutropenia, infection, anemia,
leukopenia, fatigue, hemorrhage, pyrexia, nausea, headache, febrile
neutropenia, transaminases increased, abdominal pain,
gamma-glutamyltransferase increased, and hyperbilirubinemia.1

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

The full Prescribing Information, including BOXED WARNING, for BESPONSA
can be found at

IMPORTANT BESPONSA® (inotuzumab ozogamicin)


  • Hepatotoxicity, including fatal and life-threatening VOD, occurred
    in patients who received BESPONSA.
    The risk of VOD was greater
    in patients who underwent HSCT after BESPONSA treatment. Consider
    identified risk factors. Monitor closely for signs and symptoms of VOD
  • There was a higher post-HSCT non-relapse mortality rate in patients
    receiving BESPONSA, resulting in a higher Day 100 post-HSCT mortality

Hepatotoxicity, Including VOD: Hepatotoxicity, including fatal
and life-threatening VOD, occurred in patients who received BESPONSA.
The risk of VOD was greater in patients who underwent HSCT after
BESPONSA treatment. The use of HSCT conditioning regimens containing 2
alkylating agents and last total bilirubin ≥ the upper limit of normal
(ULN) before HSCT were significantly associated with an increased risk
of VOD. Other risk factors for VOD in patients treated with BESPONSA
included ongoing or prior liver disease, prior HSCT, increased age,
later salvage lines, and a greater number of BESPONSA treatment cycles.
Grade 3/4 increases in aspartate aminotransferase (AST), alanine
aminotransferase (ALT), and total bilirubin have occurred.

Monitor closely for signs and symptoms of VOD; these may include
elevations in total bilirubin, hepatomegaly (which may be painful),
rapid weight gain, and ascites. Elevation of liver tests may require
dosing interruption, dose reduction, or permanent discontinuation of
BESPONSA. Permanently discontinue treatment if VOD occurs. If severe VOD
occurs, treat according to standard medical practice.

Increased Risk of Post-HSCT Non-Relapse Mortality: There was a
higher post-HSCT non-relapse mortality rate in patients receiving
BESPONSA, resulting in a higher Day 100 post-HSCT mortality rate. In
the BESPONSA arm, the most common causes of post-HSCT non-relapse
mortality included VOD and infections. Monitor closely for toxicities
post HSCT, including signs and symptoms of infection and VOD.

Myelosuppression: Myelosuppression, and severe, life-threatening
and fatal complications of myelosuppression, including hemorrhagic
events and infections, have occurred with BESPONSA. Thrombocytopenia,
neutropenia, and febrile neutropenia were reported.

Monitor complete blood counts prior to each dose of BESPONSA and monitor
for signs and symptoms of infection, bleeding/hemorrhage, or other
effects of myelosuppression during treatment and provide appropriate
management. As appropriate, administer prophylactic anti-infectives
during and after treatment with BESPONSA. Dose interruption, dose
reduction, or permanent discontinuation may be required.

Infusion-Related Reactions: Infusion-related reactions have
occurred in patients who received BESPONSA. Premedicate with a
corticosteroid, antipyretic, and antihistamine prior to dosing. Monitor
patients closely during and for at least 1 hour after the end of the
infusion for the potential onset of infusion-related reactions.
Interrupt the infusion and institute appropriate medical management if
an infusion-related reaction occurs. For severe or life-threatening
infusion reactions, permanently discontinue BESPONSA.

QT Interval Prolongation: Increases in QT interval have occurred.
Administer BESPONSA with caution in patients who have a history of or
predisposition to 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
treatment and after initiation of any drug known to prolong QTc, and
periodically monitor as clinically indicated during treatment.

Embryo-Fetal Toxicity and Nursing Mothers: BESPONSA can cause
embryo-fetal harm. Advise males and females of reproductive potential to
use effective contraception during BESPONSA treatment and for at least 5
and 8 months after the last dose, respectively. Advise women against
breastfeeding while receiving BESPONSA and for 2 months after the last

Adverse Reactions: The most common (≥20%) adverse reactions
observed with BESPONSA were thrombocytopenia, neutropenia, infection,
anemia, leukopenia, fatigue, hemorrhage, pyrexia, nausea, headache,
febrile neutropenia, transaminases increased, abdominal pain,
gamma-glutamyltransferase increased, and hyperbilirubinemia.

The most common (≥2%) serious adverse reactions were infection, febrile
neutropenia, hemorrhage, abdominal pain, pyrexia, VOD, and fatigue.

Please see full Prescribing Information, including BOXED WARNING here

About Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia (ALL) is an aggressive type of leukemia
with a poor prognosis in adults.2 The current foundational
treatment is intensive, long-term chemotherapy.3 In 2017, it
is estimated that 5,970 cases of ALL will be diagnosed in the United
States.4 About 4 in 10 cases occur in adults.4
While about 80-90% of adult patients will have a complete remission at
some point during initial treatment, the remainder (approximately
10%-20%) will be refractory, meaning they no longer respond to treatment.3
Additionally, about half of patients who achieve remission will relapse.3
The post relapse median survival is 4.5 to 6 months.5

About BESPONSA® (inotuzumab ozogamicin)

BESPONSA is an antibody-drug conjugate (ADC) composed of a monoclonal
antibody (mAb) targeting CD22, a cell surface antigen expressed on
cancer cells in almost all B-ALL patients, linked to a cytotoxic agent.6
When BESPONSA binds to the CD22 antigen on B-cells, it is internalized
into the cell, where the cytotoxic agent calicheamicin is released
causing cell death.7 BESPONSA is administered as a one-hour
intravenous infusion that can be given in the outpatient setting of care
for appropriate patients.

BESPONSA originates from a collaboration between Pfizer and Celltech,
now UCB. Under the terms of this agreement, Pfizer has sole
responsibility for all commercialization, manufacturing and clinical
development activities for this molecule. Pfizer also collaborated with
SFJ Pharmaceuticals Group on the registrational program (INO-VATE ALL)

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 worldTM

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
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work across developed and emerging markets to advance wellness,
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DISCLOSURE NOTICE: The information contained in this release is as of
August 17, 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 BESPONSA
(inotuzumab ozogamicin), and an approval by the FDA for the treatment of
adults with relapsed or refractory B-cell precursor acute lymphoblastic
leukemia, 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, uncertainties regarding the
commercial success of BESPONSA; 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 BESPONSA may
be filed in any other jurisdictions; whether and when any such
applications that may be pending or filed for BESPONSA 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 BESPONSA; 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

*CR/CRi includes complete remission (<5% blasts in the bone marrow and the absence of peripheral blood leukemic blasts, full recovery of peripheral blood counts and resolution of any extramedullary disease) and complete remission with incomplete recovery of peripheral blood counts.

1 BESPONSA (inotuzumab ozogamicin) Prescribing Information.
New York. NY: Pfizer Inc: 2017.

2 National Cancer Institute: Adult Acute Lymphoblastic
Leukemia Treatment (PDQ®) – General Information About Adult Acute
Lymphoblastic Leukemia (ALL). Available at:
Accessed March 23, 2017.

3 American Cancer Society: Typical treatment of acute
lymphocytic leukemia. Available at:
Accessed March 21, 2017.

4 American Cancer Society: What are the key statistics about
acute lymphocytic leukemia? Available at:
Accessed March 21, 2017.

5 National Comprehensive Cancer Network. NCCN Clinical
Practice Guidelines in Oncology (NCCN Guidelines®): Acute Lymphoblastic
Leukemia. Version 2.2016. National Comprehensive Cancer Network; 2016.
Accessed April 26, 2017.

6 Leonard J et al. Epratuzumab, a Humanized Anti-CD22
Antibody, in Aggressive Non-Hodgkin’s Lymphoma: a Phase I/II Clinical
Trial Results. Clinical Cancer Research. 2004; 10: 5327-5334.

7 DiJoseph JF. Antitumor Efficacy of a Combination of CMC-544
(Inotuzumab Ozogamicin), a CD22-Targeted Cytotoxic Immunoconjugate of
Calicheamicin, and Rituximab against Non-Hodgkin’s B-Cell Lymphoma. Clin
Cancer Res. 2006; 12: 242-250.


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