Applications seek to expand approved use of BOSULIF into first- line
treatment based on positive results from Phase 3 head-to-head trial
LONDON & NEW YORK--(BUSINESS WIRE)--
Pfizer Inc. (NYSE:PFE) and Avillion LLP today announced that a
supplemental New Drug Application (sNDA) for BOSULIF®
(bosutinib) has been accepted for filing and granted Priority Review by
the U.S. Food and Drug Administration (FDA). If approved, the sNDA would
expand the approved use of BOSULIF to include patients with newly
diagnosed chronic phase Philadelphia chromosome-positive (Ph+) chronic
myeloid leukemia (CML). BOSULIF is currently indicated in the U.S. for
the treatment of adult patients with Ph+ CML with resistance or
intolerance to prior therapy. Priority Review status accelerates FDA
review time from 10 months to a goal of six months from the day of
acceptance of filing, and is given to drugs that may offer major
advances in treatment or may provide a treatment for which no adequate
therapy exists. The Prescription Drug User Fee Act (PDUFA) goal date for
a decision by the FDA is in December 2017.
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In addition, the European Medicines Agency (EMA) has validated for
review a Type II Variation application for use of BOSULIF in the same
patient population. In Europe, BOSULIF has conditional marketing
authorization for the treatment of adult patients with Ph+ CML
previously treated with one or more tyrosine kinase inhibitors (TKIs)
and for whom imatinib, nilotinib and dasatinib are not considered
appropriate treatment options.
The submissions are based on results from BFORE (Bosutinib trial
in First line chrOnic myelogenous leukemia tREatment),
a multi-center, multinational, open-label Phase 3 study which showed
BOSULIF 400 mg was associated with a significantly higher rate of
patients achieving major molecular response (MMR) at 12 months (the
primary endpoint) compared to the rate achieved in patients treated with
imatinib. Results from the trial were presented at the American Society
of Clinical Oncology (ASCO) Annual Meeting in May 2017 and at the
European Hematology Association (EHA) Meeting in June 2017. The adverse
events seen in the trial were consistent with the known safety profile
for BOSULIF. The proposed dosing for the newly diagnosed patients is 400
mg daily, which is different from the currently approved dosing in
patients who are resistant or intolerant to prior TKI therapy (500 mg
daily).
“As physicians gained experience with BOSULIF, they have come to
appreciate its favorable risk-benefit profile in patients with
Ph-positive CML who no longer responded to or could not tolerate prior
TKI therapy,” said Mace Rothenberg, MD, Chief Development Officer,
Oncology, Pfizer Global Product Development. “At the 400 mg dose, we
believe that the BFORE study demonstrates a similarly favorable
risk-benefit in previously untreated patients with Ph-positive CML. We
look forward to working with the FDA in our efforts to expand the label
for BOSULIF to include this important group of patients.”
“These are important milestones for the CML community and for our
partnership with Pfizer, which represent the commitment of both of our
companies to work collaboratively toward our ultimate goal of improving
the lives of patients,” said Allison Jeynes-Ellis, MD, Chief Executive
Officer of Avillion.
Pfizer and Avillion entered into an exclusive collaborative development
agreement in 2014 to conduct the BFORE trial. Under the terms of the
agreement, Avillion provided funding and conducted the trial to generate
the clinical data used to support these applications and other potential
regulatory filings for marketing authorization for BOSULIF as first-line
treatment for patients with chronic phase Ph+ CML. If approved for this
indication, Avillion will be eligible to receive milestone payments from
Pfizer. Pfizer retains all rights to commercialize BOSULIF globally.
Pfizer is advancing a broad range of therapies that leverage select
pathways and mechanisms of action to address acute and chronic
leukemias, myeloproliferative disorders and lymphoma.
ABOUT CHRONIC MYELOID LEUKEMIA (CML)
Chronic myeloid leukemia (CML) is a rare blood cancer, which begins in
the bone marrow, but often moves into the blood.1 Researchers
estimate that by 2020, more than 412,000 people worldwide will be
diagnosed with leukemia (all types).2 CML accounts for 10-15%
of all incident leukemia cases.1,3 In the U.S., approximately
48,000 people are living with CML.4 Around 9,000 new CML
cases will be diagnosed in the U.S. in 2017.5
ABOUT BOSULIF® (bosutinib)
BOSULIF® (bosutinib) is an oral, once-daily, tyrosine kinase
inhibitor (TKI), which inhibits the Bcr-Abl kinase that promotes CML; it
is also an inhibitor of Src-family kinases. BOSULIF was approved in
September 2012 in the U.S. for the treatment of adult patients with Ph+
CML with resistance or intolerance to prior therapy and offers an
important treatment option for these patients. In Europe, BOSULIF was
granted conditional marketing authorization in March 2013 for the
treatment of adult patients with Ph+ CML previously treated with one or
more TKIs and for whom imatinib, nilotinib and dasatinib are not
considered appropriate treatment options. The current approved dose of
BOSULIF is 500 mg orally once daily with food. For more information on
BOSULIF resources available for healthcare professionals and patients,
please visit www.BOSULIF.com.
IMPORTANT BOSULIF® (bosutinib) SAFETY INFORMATION
Contraindication: History of hypersensitivity to BOSULIF.
Reactions have included anaphylaxis. Anaphylactic shock occurred in less
than 0.2% of treated patients in clinical trials.
Gastrointestinal Toxicity: Diarrhea, nausea, vomiting, and
abdominal pain can occur. In the clinical trial, median time to onset
for diarrhea was 2 days, median duration was 2 days, and median number
of episodes per patient was 3 (range 1-268). Monitor and manage patients
using standards of care, including antidiarrheals, antiemetics, and/or
fluid replacement. Withhold, dose reduce, or discontinue BOSULIF as
necessary.
Myelosuppression: Thrombocytopenia, anemia, and neutropenia can
occur. Perform complete blood counts weekly for the first month and then
monthly or as clinically indicated. Withhold, dose reduce, or
discontinue BOSULIF as necessary.
Hepatic Toxicity: Twenty percent of patients experienced an
increase in either ALT or AST. Liver enzyme elevation usually occurs
early in treatment. The median time to onset of increased ALT and AST
was 35 and 33 days, respectively, and the median duration for each was
21 days. Perform hepatic enzyme tests at least monthly for the first 3
months and as clinically indicated. In patients with transaminase
elevations, monitor liver enzymes more frequently. One case consistent
with drug-induced liver injury occurred in a trial of BOSULIF in
combination with letrozole. Withhold, dose reduce, or discontinue
BOSULIF as necessary. In patients with mild, moderate, or severe hepatic
impairment, the recommended starting dose is 200 mg daily.
Renal Toxicity: An on-treatment decline in estimated glomerular
filtration rate has occurred in patients treated with BOSULIF. Monitor
renal function at baseline and during therapy, with particular attention
to patients with preexisting renal impairment or risk factors for renal
dysfunction. Consider dose adjustment in patients with baseline and
treatment emergent renal impairment. The recommended starting doses for
patients with severe renal impairment (CrCL <30 mL/min) or moderate
renal impairment (CrCL 30-50 mL/min) are 300 mg and 400 mg daily,
respectively.
Fluid Retention: Fluid retention can occur and may cause
pericardial effusion, pleural effusion, pulmonary edema, and/or
peripheral edema. In the clinical trial, Grade 3/4 fluid retention was
reported in 26 patients (5%). Monitor and manage patients using
standards of care. Interrupt, dose reduce, or discontinue BOSULIF as
necessary.
Embryofetal Toxicity: BOSULIF can cause fetal harm when
administered to a pregnant woman. Women of childbearing potential should
be advised of potential hazard to the fetus. Advise females of
reproductive potential to use effective contraceptive measures to
prevent pregnancy while being treated with BOSULIF and for at least 30
days after the final dose.
Adverse Reactions: The most common adverse reactions observed in
greater than or equal to 20% of patients in the Phase 1/2 safety
population (N=546) were diarrhea, nausea, thrombocytopenia, rash,
vomiting, abdominal pain, respiratory tract infection, anemia, pyrexia,
liver test abnormalities, fatigue, cough, and headache. The most common
Grade 3/4 adverse reactions and laboratory abnormalities observed in
greater than 10% of patients were thrombocytopenia, neutropenia, and
anemia.
CYP3A Inhibitors and Inducers: Avoid concurrent use with strong
or moderate CYP3A inhibitors or inducers.
Proton Pump Inhibitors: Consider using short-acting antacids or
H2 blockers instead of PPIs to avoid a reduction in BOSULIF exposure.
Separate antacid or H2 blocker dosing and BOSULIF dosing by more than 2
hours.
Nursing Mothers: Given the potential for serious adverse
reactions in nursing infants, a decision should be made whether to
discontinue nursing or BOSULIF, taking into account the importance of
the drug to the mother.
Please see full Prescribing
Information at www.bosulif.com.
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 healthcare products. Our global portfolio
includes medicines and vaccines as well as many of the world's
best-known consumer healthcare 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
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In addition, to learn more, please visit us on www.pfizer.com
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About Avillion
Avillion LLP is a drug development company with an innovative business
model focusing on the clinical co-development and regulatory approval of
late stage pharmaceutical products. Avillion offers a compelling
opportunity to partner late-stage therapeutic projects for approval in
the US and EU and to accelerate their availability to the market. Our
objective is to enable our partners to continue to develop the drug
candidates in their pipeline at the highest quality without increasing
the burden on their P&L or cash reserves. Avillion can achieve this by
incurring 100% of the clinical and regulatory risk, while advancing the
development of these late-stage assets in return for milestone payments
on the commercialisation of successfully developed products.
Avillion was founded in 2012 in London, UK, and is backed by Abingworth,
Clarus Ventures and Royalty Pharma. http://www.avillionllp.com
PFIZER DISCLOSURE NOTICE: The information contained in this release
is as of August 29, 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 a potential
new indication for BOSULIF (bosutinib), 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 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;
uncertainties regarding the commercial success of BOSULIF; whether and
when any applications for the potential indication may be filed with
regulatory authorities in any other jurisdictions; whether and when the
FDA and EMA will approve the sNDA and Type II Variation application,
respectively, for the potential indication and whether and when
regulatory authorities in any jurisdictions may approve any such other
applications, 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 BOSULIF, including the potential
indication; 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 American Cancer Society. What is Chronic Myeloid Leukemia? http://www.cancer.org/acs/groups/cid/documents/webcontent/003112-pdf.pdf.
Accessed August 2017.
2 GLOBOCAN Online Analysis/Prediction. http://globocan.iarc.fr/old/burden.asp?selection_pop=224900&Text-p=World&selection_cancer=12280&Text-c=Leukaemia&pYear=8&type=0&window=1&submit=%C2%A0Execute.
Accessed August 2017.
3 Hochhaus, A. Educational Session: Managing Chronic Myeloid
Leukemia as a Chronic Disease. American Society of Hematology. 2011; 10:
1.
4 National Cancer Institute. Surveillance Epidemiology and
End Results (SEER) Statistics Stratified by Cancer Site: Chronic Myeloid
Leukemia Prevalence. http://seer.cancer.gov/faststats/selections.php?run=runit&output=2&data=5&statistic=9&race=1&sex=1&age=1&series=cancer&cancer=97.
Accessed August 2017.
5 American Cancer Society. What Are the Key Statistics About
Chronic Myeloid Leukemia? https://www.cancer.org/cancer/chronic-myeloid-leukemia/about/statistics.html.
Accessed August 2017.
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Source: Pfizer Inc.