DARMSTADT, Germany and NEW YORK, March 19, 2019 /PRNewswire/ --
Not intended for UK-based media
Merck KGaA, Darmstadt, Germany, which operates its biopharmaceutical business as EMD Serono
in the US and Canada, and Pfizer Inc. (NYSE: PFE) today announced the discontinuation of
the ongoing Phase III JAVELIN Ovarian PARP 100 study evaluating the efficacy and safety of avelumab in combination with
chemotherapy followed by maintenance therapy of avelumab in combination with talazoparib,* a poly (ADP-ribose) polymerase (PARP)
inhibitor, versus an active comparator in treatment-naïve patients with locally advanced or metastatic ovarian cancer (Stage III
or Stage IV). The alliance has notified health authorities and trial investigators of the decision to discontinue the trial.
The decision was based on several emerging factors since the trial's initiation, including the previously announced
interim results from JAVELIN Ovarian PARP 100. The alliance determined that the degree of benefit observed with avelumab in
frontline ovarian cancer in that study does not support continuation of the JAVELIN Ovarian PARP 100 trial in an unselected
patient population and emphasizes the need to better understand the role of immunotherapy in ovarian cancer. Additional factors
include the rapidly changing treatment landscape and the approval of a PARP inhibitor in the frontline maintenance
setting. The decision to discontinue the JAVELIN Ovarian PARP 100 trial was not made for safety reasons.
The alliance between Merck KGaA, Darmstadt, Germany, and Pfizer was the first to test an
immunotherapy in this indication, given the significant unmet need in the treatment of ovarian cancer. Four out of five women
with ovarian cancer are diagnosed with disease that has spread to the lymph nodes or to distant organs.1 Most women
with advanced ovarian cancer ultimately die within five years due to refractory, resistant or recurrent
disease.2,3
JAVELIN Ovarian PARP 100 (B9991030) is an open-label, international, multi-center, randomized study designed to evaluate the
efficacy and safety of avelumab in combination with chemotherapy followed by maintenance therapy of avelumab in combination with
talazoparib versus an active comparator in treatment-naïve patients with locally advanced or metastatic ovarian cancer (Stage III
or Stage IV). The primary endpoint is progression-free survival (PFS) as determined based on blinded independent central review
(BICR) assessment per RECIST v1.1.
The decision to discontinue the JAVELIN Ovarian PARP 100 trial does not impact the currently approved indications for avelumab
or the remainder of the ongoing JAVELIN clinical development program. The program involves at least 30 clinical programs and more
than 9,000 patients evaluated across more than 15 different tumor types, including breast, gastric/gastro-esophageal junction,
and head and neck cancers, Merkel cell carcinoma, non-small cell lung cancer, and urothelial carcinoma.
*Avelumab and talazoparib are under clinical investigation for the treatment of advanced ovarian cancer and have not been
demonstrated to be safe and effective for this use.
About Avelumab (BAVENCIO®)
Avelumab (BAVENCIO®) is a human anti-programmed death ligand-1 (PD-L1) antibody. Avelumab has been shown in
preclinical models to engage both the adaptive and innate immune functions. By blocking the interaction of PD-L1 with PD-1
receptors, avelumab has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical
models.4-6 Avelumab has also been shown to induce NK cell-mediated direct tumor cell lysis via antibody-dependent
cell-mediated cytotoxicity (ADCC) in vitro.6-8 In November 2014, Merck KGaA,
Darmstadt, Germany, and Pfizer announced a strategic alliance to co-develop and co-commercialize
avelumab.
Approved Indications in the US
In the US, the FDA granted accelerated approval for avelumab (BAVENCIO®) for the treatment of (i) adults and
pediatric patients 12 years and older with metastatic Merkel cell carcinoma (mMCC) and (ii) patients with locally advanced or
metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy, or have
disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. These
indications are approved under accelerated approval based on tumor response rate and duration of response. Continued approval for
these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.
Avelumab is currently approved for patients with MCC in more than 45 countries globally, with the majority of these approvals
in a broad indication that is not limited to a specific line of treatment.
Important Safety Information from the BAVENCIO® US FDA-Approved Label
BAVENCIO can cause immune-mediated pneumonitis, including fatal cases. Monitor patients for signs and symptoms of
pneumonitis, and evaluate suspected cases with radiographic imaging. Administer corticosteroids for Grade 2 or greater
pneumonitis. Withhold BAVENCIO for moderate (Grade 2) and permanently discontinue for severe (Grade 3), life-threatening (Grade
4), or recurrent moderate (Grade 2) pneumonitis. Pneumonitis occurred in 1.2% (21/1738) of patients, including one (0.1%) patient
with Grade 5, one (0.1%) with Grade 4, and five (0.3%) with Grade 3.
BAVENCIO can cause immune-mediated hepatitis, including fatal cases. Monitor patients for abnormal liver tests prior to
and periodically during treatment. Administer corticosteroids for Grade 2 or greater hepatitis. Withhold BAVENCIO for moderate
(Grade 2) immune-mediated hepatitis until resolution and permanently discontinue for severe (Grade 3) or life-threatening (Grade
4) immune-mediated hepatitis. Immune-mediated hepatitis was reported in 0.9% (16/1738) of patients, including two (0.1%) patients
with Grade 5, and 11 (0.6%) with Grade 3.
BAVENCIO can cause immune-mediated colitis. Monitor patients for signs and symptoms of colitis. Administer
corticosteroids for Grade 2 or greater colitis. Withhold BAVENCIO until resolution for moderate or severe (Grade 2 or 3) colitis,
and permanently discontinue for life-threatening (Grade 4) or recurrent (Grade 3) colitis upon reinitiation of BAVENCIO.
Immune-mediated colitis occurred in 1.5% (26/1738) of patients, including seven (0.4%) with Grade 3.
BAVENCIO can cause immune-mediated endocrinopathies, including adrenal insufficiency, thyroid disorders, and type 1
diabetes mellitus.
Monitor patients for signs and symptoms of adrenal insufficiency during and after treatment, and administer
corticosteroids as appropriate. Withhold BAVENCIO for severe (Grade 3) or life-threatening (Grade 4) adrenal insufficiency.
Adrenal insufficiency was reported in 0.5% (8/1738) of patients, including one (0.1%) with Grade 3.
Thyroid disorders can occur at any time during treatment. Monitor patients for changes in thyroid function at the
start of treatment, periodically during treatment, and as indicated based on clinical evaluation. Manage hypothyroidism with
hormone replacement therapy and hyperthyroidism with medical management. Withhold BAVENCIO for severe (Grade 3) or
life-threatening (Grade 4) thyroid disorders. Thyroid disorders, including hypothyroidism, hyperthyroidism, and thyroiditis, were
reported in 6% (98/1738) of patients, including three (0.2%) with Grade 3.
Type 1 diabetes mellitus including diabetic ketoacidosis: Monitor patients for hyperglycemia or other signs and
symptoms of diabetes. Withhold BAVENCIO and administer antihyperglycemics or insulin in patients with severe or life-threatening
(Grade ≥ 3) hyperglycemia, and resume treatment when metabolic control is achieved. Type 1 diabetes mellitus without an
alternative etiology occurred in 0.1% (2/1738) of patients, including two cases of Grade 3 hyperglycemia.
BAVENCIO can cause immune-mediated nephritis and renal dysfunction. Monitor patients for elevated serum creatinine
prior to and periodically during treatment. Administer corticosteroids for Grade 2 or greater nephritis. Withhold BAVENCIO for
moderate (Grade 2) or severe (Grade 3) nephritis until resolution to Grade 1 or lower. Permanently discontinue BAVENCIO for
life-threatening (Grade 4) nephritis. Immune-mediated nephritis occurred in 0.1% (1/1738) of patients.
BAVENCIO can result in other severe and fatal immune-mediated adverse reactions involving any organ system during
treatment or after treatment discontinuation. For suspected immune-mediated adverse reactions, evaluate to confirm or rule out an
immune-mediated adverse reaction and to exclude other causes. Depending on the severity of the adverse reaction, withhold or
permanently discontinue BAVENCIO, administer high-dose corticosteroids, and initiate hormone replacement therapy, if appropriate.
Resume BAVENCIO when the immune-mediated adverse reaction remains at Grade 1 or lower following a corticosteroid taper.
Permanently discontinue BAVENCIO for any severe (Grade 3) immune-mediated adverse reaction that recurs and for any
life-threatening (Grade 4) immune-mediated adverse reaction. The following clinically significant immune-mediated adverse
reactions occurred in less than 1% of 1738 patients treated with BAVENCIO: myocarditis with fatal cases, myositis, psoriasis,
arthritis, exfoliative dermatitis, erythema multiforme, pemphigoid, hypopituitarism, uveitis, Guillain-Barré syndrome, and
systemic inflammatory response.
BAVENCIO can cause severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions. Patients should be
premedicated with an antihistamine and acetaminophen prior to the first 4 infusions and for subsequent doses based upon clinical
judgment and presence/severity of prior infusion reactions. Monitor patients for signs and symptoms of infusion-related
reactions, including pyrexia, chills, flushing, hypotension, dyspnea, wheezing, back pain, abdominal pain, and urticaria.
Interrupt or slow the rate of infusion for mild (Grade 1) or moderate (Grade 2) infusion-related reactions. Permanently
discontinue BAVENCIO for severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions. Infusion-related reactions
occurred in 25% (439/1738) of patients, including three (0.2%) patients with Grade 4 and nine (0.5%) with Grade 3.
BAVENCIO can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to a fetus
including the risk of fetal death. Advise females of childbearing potential to use effective contraception during treatment with
BAVENCIO and for at least 1 month after the last dose of BAVENCIO. It is not known whether BAVENCIO is excreted in human milk.
Advise a lactating woman not to breastfeed during treatment and for at least 1 month after the last dose of BAVENCIO due
to the potential for serious adverse reactions in breastfed infants.
The most common adverse reactions (all grades, ≥ 20%) in patients with metastatic Merkel cell carcinoma
(MCC) were fatigue (50%), musculoskeletal pain (32%), diarrhea (23%), nausea (22%), infusion-related reaction (22%), rash
(22%), decreased appetite (20%), and peripheral edema (20%).
Selected treatment-emergent laboratory abnormalities (all grades, ≥ 20%) in patients with metastatic MCC
were lymphopenia (49%), anemia (35%), increased aspartate aminotransferase (34%), thrombocytopenia (27%), and increased alanine
aminotransferase (20%).
The most common adverse reactions (all grades, ≥ 20%) in patients with locally advanced or metastatic
urothelial carcinoma (UC) were fatigue (41%), infusion-related reaction (30%), musculoskeletal pain (25%), nausea (24%),
decreased appetite/hypophagia (21%), and urinary tract infection (21%).
Selected laboratory abnormalities (Grades 3-4, ≥ 3%) in patients with locally advanced or metastatic UC
were hyponatremia (16%), increased gamma-glutamyltransferase (12%), lymphopenia (11%), hyperglycemia (9%), increased alkaline
phosphatase (7%), anemia (6%), increased lipase (6%), hyperkalemia (3%), and increased aspartate aminotransferase (3%).
Please see full US Prescribing Information and Medication Guide available at http://www.BAVENCIO.com.
Indication for talazoparib (TALZENNA®) from the US Prescribing Information
TALZENNA is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated for the treatment of adult patients with deleterious or
suspected deleterious germline breast cancer susceptibility gene (BRCA)-mutated (gBRCAm) human epidermal growth factor
receptor 2 (HER2)-negative locally advanced or metastatic breast cancer. Select patients for therapy based on an FDA-approved
companion diagnostic for TALZENNA.
Important Safety Information from the TALZENNA US Prescribing Information
Myelodysplastic Syndrome/Acute Myeloid Leukemia (MDS/AML) have been reported in patients who received TALZENNA.
Overall, MDS/AML have been reported in 2 out of 584 (0.3%) solid tumor patients treated with TALZENNA in clinical studies.
Myelosuppression consisting of anemia, leukopenia/neutropenia, and/or thrombocytopenia have been reported in patients
treated with TALZENNA. Grade ≥3 anemia, neutropenia, and thrombocytopenia were reported, respectively, in 39%, 21%, and 15% of
patients receiving TALZENNA. Discontinuation due to anemia, neutropenia, and thrombocytopenia occurred, respectively, in 0.7%,
0.3%, and 0.3% of patients.
Monitor complete blood counts for cytopenia at baseline and monthly thereafter. Do not start TALZENNA until patients
have adequately recovered from hematological toxicity caused by previous therapy. If hematological toxicity occurs, dose
modifications (dosing interruption with or without dose reduction) are recommended. With respect to MDS/AML, for prolonged
hematological toxicities, interrupt TALZENNA and monitor blood counts weekly until recovery. If the levels have not recovered
after 4 weeks, refer the patient to a hematologist for further investigations. If MDS/AML is confirmed, discontinue TALZENNA.
TALZENNA can cause fetal harm when administered to pregnant women. Advise women of reproductive potential to use
effective contraception during treatment and for at least 7 months following the last dose. A pregnancy test is recommended for
females of reproductive potential prior to initiating TALZENNA treatment. Advise male patients with female partners of
reproductive potential or who are pregnant to use effective contraception during treatment with TALZENNA and for at least
4 months after receiving the last dose. Based on animal studies, TALZENNA may impair fertility in males of reproductive
potential. Advise women not to breastfeed while taking TALZENNA and for at least 1 month after receiving the last dose because of
the potential for serious adverse reactions in nursing infants.
The most common adverse reactions (≥20%) of any grade for TALZENNA vs chemotherapy were fatigue (62% vs 50%),
anemia (53% vs 18%), nausea (49% vs 47%), neutropenia (35% vs 43%), headache (33% vs 22%), thrombocytopenia (27% vs 7%), vomiting
(25% vs 23%), alopecia (25% vs 28%), diarrhea (22% vs 26%), and decreased appetite (21% vs 22%).
The most frequently reported Grade ≥3 adverse reactions (≥5%) for TALZENNA vs chemotherapy were anemia (39%
vs 5%), neutropenia (21% vs 36%), and thrombocytopenia (15% vs 2%).
The most common lab abnormalities (≥25%) for TALZENNA vs chemotherapy were decreases in hemoglobin (90% vs 77%),
leukocytes (84% vs 73%), lymphocytes (76% vs 53%), neutrophils (68% vs 70%), platelets (55% vs 29%), and calcium (28% vs 16%) and
increases in glucose (54% vs 51%), aspartate aminotransferase (37% vs 48%), alkaline phosphatase (36% vs 34%), and alanine
aminotransferase (33% vs 37%).
Coadministration with P-gp inhibitors or BCRP inhibitors may increase TALZENNA exposure. If coadministering with
the P-gp inhibitors amiodarone, carvedilol, clarithromycin, itraconazole, or verapamil is unavoidable, reduce the TALZENNA dose
to 0.75 mg once daily. When the P-gp inhibitor is discontinued, increase the TALZENNA dose (after 3–5 half-lives of the P-gp
inhibitor) to the dose used prior to the initiation of the P-gp inhibitor. When co-administering TALZENNA with other known P-gp
inhibitors or BCRP inhibitors, monitor patients for potential increased adverse reactions.
For patients with moderate renal impairment, the recommended dose of TALZENNA is 0.75 mg once daily. No dose
adjustment is required for patients with mild renal impairment. TALZENNA has not been studied in patients with severe renal
impairment or in patients requiring hemodialysis.
TALZENNA has not been studied in patients with moderate or severe hepatic impairment. No dose adjustment is
required for patients with mild hepatic impairment.
Please see full US Prescribing
Information available at http://www.TALZENNA.com.
Alliance between Merck KGaA, Darmstadt, Germany, and Pfizer Inc., New York, US
Immuno-oncology is a top priority for Merck KGaA, Darmstadt, Germany, and Pfizer. The global
strategic alliance between Merck KGaA, Darmstadt, Germany, and Pfizer enables the companies to
benefit from each other's strengths and capabilities and further explore the therapeutic potential of BAVENCIO, an anti-PD-L1
antibody initially discovered and developed by Merck KGaA, Darmstadt, Germany. The
immuno-oncology alliance is jointly developing and commercializing BAVENCIO. The alliance is focused on developing high-priority
international clinical programs to investigate BAVENCIO as a monotherapy as well as combination regimens, and is striving to find
new ways to treat cancer.
All Merck KGaA, Darmstadt, Germany, press releases are distributed by e-mail at the same time
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About Merck KGaA, Darmstadt, Germany
Merck KGaA, Darmstadt, Germany, a leading science and technology company, operates across
healthcare, life science and performance materials. Around 52,000 employees work to make a positive difference to millions of
people's lives every day by creating more joyful and sustainable ways to live. From advancing gene editing technologies and
discovering unique ways to treat the most challenging diseases to enabling the intelligence of devices – the company is
everywhere. In 2018, Merck KGaA, Darmstadt, Germany, generated sales of € 14.8 billion in 66
countries.
The company holds the global rights to the name and trademark "Merck" internationally. The only exceptions are the United States and Canada, where the business sectors of Merck KGaA,
Darmstadt, Germany operate as EMD Serono in healthcare, MilliporeSigma in life science, and EMD
Performance Materials. Since its founding 1668, scientific exploration and responsible entrepreneurship have been key to the
company's technological and scientific advances. To this day, the founding family remains the majority owner of the publicly
listed company.
Pfizer Inc.: Working together for a healthier world®
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 investors on our website
at www.pfizer.com. In addition, to learn more, please
visit us on www.pfizer.com and follow us on Twitter
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Pfizer Disclosure Notice
The information contained in this release is as of March 19, 2019. 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 avelumab (BAVENCIO), the Merck KGaA, Darmstadt, Germany-Pfizer
Alliance involving avelumab, and clinical development plans, including their 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 avelumab; the uncertainties
inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or
completion dates for our clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as
the possibility of unfavorable new clinical data and further analyses of existing clinical data; risks associated with interim
data; the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities;
whether regulatory authorities will be satisfied with the design of and results from our clinical studies; whether and when any
drug applications may be filed in any jurisdictions for any potential indications for avelumab, combination therapies or
talazoparib; whether and when regulatory authorities in any jurisdictions where applications are pending or may be submitted for
avelumab, combination therapies or talazoparib may approve any such applications, which will depend on myriad factors, including
making a determination as to whether the product's benefits outweigh its known risks and determination of the product's efficacy,
and, if approved, whether they will be commercially successful; decisions by regulatory authorities impacting labeling, safety,
manufacturing processes and/or other matters that could affect the availability or commercial potential of avelumab, combination
therapies or talazoparib; 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, 2018, 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.
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Merck KGaA, Darmstadt, Germany
Media Relations: +49-6151-72-6328, friederike.segeberg@emdgroup.com
Investor Relations: +49-6151-72-3321, investor.relations@emdgroup.com
Pfizer
Media Relations: +1-212-733-6213, jessica.m.smith@pfizer.com
Investor Relations: +1-212-733-8160, ryan.crowe@pfizer.com
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