DARMSTADT, Germany and NEW YORK, December 21, 2018 /PRNewswire/ --
Not intended for US, Canada and UK-based media
Merck and Pfizer Inc. (NYSE: PFE) today announced that data from a planned interim analysis of the Phase III JAVELIN Ovarian
100 study of avelumab* did not support the study's initial hypothesis, and therefore the alliance made the decision to terminate
the trial in alignment with the independent Data Monitoring Committee.
The Merck-Pfizer alliance 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 at advanced
stages.[1] Most women with advanced ovarian cancer ultimately die within five years due to
refractory, resistant or recurrent
disease.[2],[3]
Topline results showed that the study, which is evaluating avelumab in combination with and/or following platinum-based
chemotherapy in previously untreated patients with ovarian cancer, would not achieve superiority in the pre-specified primary
endpoint of progression-free survival. While detailed analyses of the data are ongoing, no new safety signals were observed, and
the safety profile for avelumab in this trial appears consistent with that observed in the overall JAVELIN clinical development
program. The alliance has notified health authorities and trial investigators of the interim findings and the decision to
discontinue the trial. Detailed results will be shared with the scientific community. The JAVELIN Ovarian PARP 100
study and earlier phase studies investigating avelumab in various combinations are ongoing.
*Avelumab is under clinical investigation for treatment of ovarian cancer. There is no guarantee that avelumab will be
approved for ovarian cancer by any health authority worldwide.
About JAVELIN Ovarian 100
JAVELIN Ovarian 100 is a Phase III, multicenter, randomized, three-arm study investigating avelumab in combination with and/or
as a maintenance treatment following carboplatin/paclitaxel chemotherapy in 998 previously untreated patients with locally
advanced or metastatic (Stage III or Stage IV) epithelial ovarian cancer, fallopian tube cancer (FTC), or primary peritoneal
cancer. The three arms are carboplatin/paclitaxel followed by observation; carboplatin/paclitaxel followed by avelumab
maintenance; and avelumab plus carboplatin/paclitaxel followed by avelumab maintenance. The primary objectives are to demonstrate
superior PFS for one or both avelumab-based treatment regimens compared with carboplatin/paclitaxel followed by observation.
About the JAVELIN Clinical Development Program
The clinical development program for avelumab, known as JAVELIN, involves at least 30 clinical programs and more than 9,000
patients evaluated across more than 15 different tumor types. In addition to ovarian cancer, these tumor types include breast,
gastric/gastro-esophageal junction and head and neck cancers, Merkel cell carcinoma, non-small cell lung cancer, renal cell
carcinoma and urothelial carcinoma.
About Ovarian Cancer
Every year, more than 295,000 women are diagnosed with ovarian cancer worldwide.[4] The disease is
generally advanced when it is diagnosed, as it often has few to no symptoms at the early stages, making it difficult to detect.
Symptoms also can be vague or non-specific, making it easy to confuse with less serious non-cancerous conditions. The five-year
survival rate ranges from approximately 30% to 50%, but for those with metastatic disease, it drops to less than
20%.[5],[6]
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.[7]-[9] Avelumab has also been shown to induce NK cell-mediated
direct tumor cell lysis via antibody-dependent cell-mediated cytotoxicity (ADCC) in
vitro.[9]-[11] In November
2014, Merck 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 US FDA-Approved Label
The warnings and precautions for BAVENCIO® include immune-mediated adverse reactions (such as pneumonitis,
hepatitis, colitis, endocrinopathies, nephritis and renal dysfunction, and other adverse reactions), infusion-related reactions
and embryo-fetal toxicity.
Common adverse reactions (reported in at least 20% of patients) in patients treated with avelumab for mMCC and patients with
locally advanced or mUC include fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, peripheral edema,
decreased appetite/hypophagia, urinary tract infection and rash.
About Merck-Pfizer Alliance
Immuno-oncology is a top priority for Merck and Pfizer. The global strategic alliance between Merck and Pfizer enables the
companies to benefit from each other's strengths and capabilities and further explore the therapeutic potential of avelumab, an
anti-PD-L1 antibody initially discovered and developed by Merck. The immuno-oncology alliance is jointly developing and
commercializing avelumab and advancing Pfizer's PD-1 antibody. The alliance is focused on developing high-priority international
clinical programs to investigate avelumab as a monotherapy as well as combination regimens, and is striving to find new ways to
treat cancer.
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About Merck
Merck, a vibrant science and technology company, operates across healthcare, life science and performance materials. Around
51,000 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 - Merck is everywhere. In 2017, Merck generated sales of € 15.3 billion in 66
countries.
Scientific exploration and responsible entrepreneurship have been key to Merck's technological and scientific advances. This
is how Merck has thrived since its founding in 1668. The founding family remains the majority owner of the publicly listed
company. Merck holds the global rights to the Merck name and brand. The only exceptions are the United
States and Canada, where the business sectors of Merck operate as EMD Serono in
healthcare, MilliporeSigma in life science, and EMD Performance Materials. For more information about Merck visit http://www.merckgroup.com.
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 http://www.pfizer.com. In addition, to learn more, please visit us
on http://www.pfizer.com and follow us on Twitter at @Pfizer and
@Pfizer_News, LinkedIn, YouTube and like us on Facebook at Facebook.com/Pfizer.
Pfizer Disclosure Notice
The information contained in this release is as of December 21, 2018. 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, including clinical trials evaluating avelumab for the
treatment of ovarian cancer, the Merck-Pfizer Alliance involving anti-PD-L1 and anti-PD-1 therapies, 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 study commencement and completion dates and regulatory submission dates, as well as the
possibility of unfavorable study results, including unfavorable new clinical data and additional analyses of existing clinical
data; risks associated with interim data; the risk that clinical trial data are subject to differing interpretations, and, even
when we view data as sufficient to support the safety and/or effectiveness of a product candidate, regulatory authorities may not
share our views and may require additional data or may deny approval altogether; 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 other product candidates; whether and when
regulatory authorities in any jurisdictions where applications are pending or may be submitted for avelumab, combination
therapies or other product candidates may approve any such 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
avelumab, combination therapies or other product candidates; 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, 2017, 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 http://www.sec.gov and http://www.pfizer.com.
References
- American Cancer Society. Survival Rates for Ovarian Cancer, by Stage. Available at: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2018/cancer-facts-and-figures-special-section-ovarian-cancer-2018.pdf.
Accessed December 2018.
- Ledermann, JA, Raja FA, Fotopoulou C, et al. Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO Clinical
Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013; 24 (Supplement 6): vi24-vi32,
doi:10.1093/annonc/mdt333.
- Ozol, RJ. Challenges for chemotherapy in ovarian cancer. Annals of Oncology 2006;17(5):v181-187.
- World Cancer Research Fund / American Institute for Cancer Research. Continuous Update
Project. Available at: https://www.wcrf.org/dietandcancer/cancer-trends/worldwide-cancer-data. Accessed December
2018.
- World Cancer Research Fund / American Institute for Cancer Research. Continuous Update
Project. Available at: https://www.wcrf.org/dietandcancer/ovarian-cancer. Accessed December
2018.
- American Cancer Society. Survival Rates for Ovarian Cancer, by Stage. Available at:
https://www.cancer.org/cancer/ovarian-cancer/detection-diagnosis-staging/survival-rates.html. Accessed
December 2018.
- Dolan DE, Gupta S. PD-1 pathway inhibitors: changing the landscape of cancer
immunotherapy. Cancer Control. 2014;21(3):231-237.
- Dahan R, Sega E, Engelhardt J, et al. Fc?Rs modulate the anti-tumor activity of antibodies targeting the PD-1/PD-L1 axis.
Cancer Cell. 2015;28(3):285-295.
- Boyerinas B, Jochems C, Fantini M, et al. Antibody-dependent cellular cytotoxicity activity of a novel anti-PD-L1 antibody
avelumab (MSB0010718C) on human tumor cells. Cancer Immunol Res. 2015;3(10):1148-1157.
- Kohrt HE, Houot R, Marabelle A, et al. Combination strategies to enhance antitumor ADCC. Immunotherapy.
2012;4(5):511-527.
- Hamilton G, Rath B. Avelumab: combining immune checkpoint inhibition and antibody-dependent cytotoxicity. Expert
Opin Biol Ther. 2017;17(4):515-523.
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