FDA Accepts sBLA and Grants Priority Review for BAVENCIO(R) (avelumab) Plus INLYTA(R) (axitinib) for the Treatment of Advanced Renal Cell Carcinoma

PR77403

DARMSTADT, Germany and NEW YORK, Feb. 11, 2019 /PRNewswire=KYODO JBN/ --

     Not intended for US, Canada and UK-based media

    Merck and Pfizer Inc. (NYSE: PFE) today announced that the US Food and Drug

Administration (FDA) has accepted for Priority Review the supplemental

Biologics License Application (sBLA) for BAVENCIO(R) (avelumab) in combination

with INLYTA(R) (axitinib)* for patients with advanced renal cell carcinoma

(RCC). The application has been given a target action date in June 2019.

    "The combination of BAVENCIO with INLYTA builds on Pfizer's significant

heritage in advancing standards of care for patients with advanced RCC and has

the potential to make a meaningful impact for the lives of patients," said

Chris Boshoff, M.D., Ph.D., Chief Development Officer, Oncology, Pfizer Global

Product Development. "We look forward to working with the FDA to bring this

potential new treatment option to patients as quickly as possible."

    "Our alliance is focused on the development of potential new treatment

options for patients with cancers that have high unmet medical needs, including

the broad spectrum of people living with advanced RCC," said Luciano Rossetti,

M.D., Executive Vice President, Head of Global Research & Development at the

Biopharma business of Merck. "This regulatory milestone, which closely follows

the acceptance of our application in Japan, represents an important step

forward for science and for patients."

    The submission is based on data from the pivotal Phase III JAVELIN Renal

101 trial, which were presented in a Presidential Symposium at the European

Society of Medical Oncology (ESMO) 2018 Congress in Munich. In December 2017,

the FDA granted Breakthrough Therapy Designation for BAVENCIO in combination

with INLYTA for treatment-naïve patients with advanced RCC.

    Despite available therapies, the outlook for patients with advanced RCC

remains poor. [1] Approximately 20% to 30% of patients are first diagnosed at

the metastatic stage.[2]  The five-year survival rate for patients with

metastatic RCC is approximately 12%.[1]

    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 RCC, these tumor types

include breast, gastric/gastro-esophageal junction, and head and neck cancers,

Merkel cell carcinoma, non-small cell lung cancer, and urothelial carcinoma.

    *The combination of BAVENCIO and INLYTA is under clinical investigation for

advanced RCC, and there is no guarantee this combination will be approved for

advanced RCC by any health authority worldwide. In the US, INLYTA is approved

as monotherapy for the treatment of advanced RCC after failure of one prior

systemic therapy. INLYTA is also approved by the European Medicines Agency

(EMA) for use in the EU in adult patients with advanced RCC after failure of

prior treatment with SUTENT(R) (sunitinib) or a cytokine.

    About Renal Cell Carcinoma

    RCC is the most common form of kidney cancer, accounting for about 2% to 3%

of all cancers in adults.[3],[4] The most common type of RCC is clear cell

carcinoma, accounting for approximately 70% of all cases.[3] In 2019, an

estimated 73,820 new cases of kidney cancer will be diagnosed in the US.[5]

    About BAVENCIO(R) (avelumab)

    BAVENCIO is a human anti-programmed death ligand-1 (PD-L1) antibody.

BAVENCIO 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, BAVENCIO has been shown to release the suppression of the T

cell-mediated antitumor immune response in preclinical models.[6] -[8] BAVENCIO

has also been shown to induce NK cell-mediated direct tumor cell lysis via

antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro.[8]-[10] In

November 2014, Merck and Pfizer announced a strategic alliance to co-develop

and co-commercialize BAVENCIO.

    Approved Indications in the US

    In the US, the FDA granted accelerated approval for 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.

    BAVENCIO 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 INLYTA(R) (axitinib)

    INLYTA is an oral therapy that is designed to inhibit tyrosine kinases,

including vascular endothelial growth factor (VEGF) receptors 1, 2 and 3; these

receptors can influence tumor growth, vascular angiogenesis and progression of

cancer (the spread of tumors). In the US, INLYTA is approved for the treatment

of advanced renal cell carcinoma (RCC) after failure of one prior systemic

therapy. INLYTA is also approved by the European Medicines Agency (EMA) for use

in the EU in adult patients with advanced RCC after failure of prior treatment

with sunitinib or a cytokine.

    INLYTA Important Safety Information from the US FDA Approved Label

    In the study of advanced RCC after failure of one prior systemic therapy,

the warnings and precautions for INLYTA include hypertension, including

hypertensive crisis, arterial and venous thrombotic events, hemorrhagic events,

cardiac failure, gastrointestinal perforation and fistula, hypothyroidism,

wound healing complications, reversible posterior leukoencephalopathy syndrome

(RPLS), proteinuria, liver enzyme elevation, hepatic impairment, and fetal harm

during pregnancy.

    Common adverse events (reported in at least 20% of patients) in patients

receiving INLYTA were diarrhea, hypertension, fatigue, decreased appetite,

nausea, dysphonia, hand-foot syndrome, weight decreased, vomiting, asthenia,

and constipation.

    For more information and full Prescribing Information, visit www.INLYTA.com

[http://www.INLYTA.com ].

    About SUTENT(R) (sunitinib malate)

    Sunitinib is a small molecule that inhibits multiple receptor tyrosine

kinases, some of which are implicated in tumor growth, pathologic angiogenesis,

and metastatic progression of cancer. Sunitinib was evaluated for its

inhibitory activity against a variety of kinases (>80 kinases) and was

identified as an inhibitor of platelet-derived growth factor receptors

(PDGFRalpha and PDGFRbeta), vascular endothelial growth factor receptors

(VEGFR1, VEGFR2 and VEGFR3), stem cell factor receptor (KIT), Fms-like tyrosine

kinase-3 (FLT3), colony stimulating factor receptor Type 1 (CSF-1R), and the

glial cell-line derived neurotrophic factor receptor (RET).

    SUTENT is indicated in the US for the treatment of gastrointestinal stromal

tumor (GIST) after disease progression on or intolerance to imatinib mesylate;

the treatment of advanced RCC; the adjuvant treatment of adult patients at high

risk of recurrent RCC following nephrectomy; and the treatment of progressive,

well-differentiated pancreatic neuroendocrine tumors (pNET) in patients with

unresectable locally advanced or metastatic disease.

    SUTENT Important Safety Information from the US FDA Approved Label

    Boxed Warning/Hepatotoxicity has been observed in clinical trials and

postmarketing experience. Hepatotoxicity may be severe, and in some cases

fatal. Monitor hepatic function and interrupt, reduce, or discontinue dosing as

recommended. Fatal liver failure has been observed. Monitor liver function

tests before initiation of treatment, during each cycle of treatment, and as

clinically indicated. Interrupt SUTENT for Grade 3 or 4 drug-related hepatic

adverse reactions and discontinue if there is no resolution. Do not restart

SUTENT if patients subsequently experience severe changes in liver function

tests or have signs and symptoms of liver failure.

    Additional warnings and precautions for SUTENT include cardiovascular

events, QT prolongation and Torsades de Pointes, hypertension, hemorrhagic

events, tumor lysis syndrome (TLS), thrombotic microangiopathy (TMA),

proteinuria, dermatologic toxicities including erythema multiforme,

Sevens-Johnson syndrome, and toxic epidermal necrolysis, necrotizing fasciitis,

thyroid dysfunction, hypoglycemia, osteonecrosis of the jaw (ONJ), impaired

wound healing, embryo fetal toxicity and impaired reproductive potential,

potential harm during lactation, venous thromboembolic events, reversible

posterior leukoencephalopathy syndrome (RPLS), and pancreatic function.

    Common adverse reactions (reported in at least 20% of patients) in patients

receiving SUTENT for treatment-naïve metastatic RCC were diarrhea, fatigue,

nausea, anorexia, altered taste, mucositis/stomatitis, pain in extremity/limb

discomfort, vomiting, bleeding,  all sites, hypertension, dyspepsia,

arthralgia, abdominal pain, rash, hand-foot syndrome, back pain, cough,

asthenia, dyspnea, skin discoloration/yellow skin, peripheral edema, headache,

constipation, dry skin, fever, and hair color changes.

    Common adverse reactions (reported in at least 20% of patients) in patients

receiving SUTENT for adjuvant treatment of RCC, GIST or pNET - and more

commonly than in patients given placebo - were mucositis/stomatitis/oral

syndromes, diarrhea, fatigue, asthenia, hand-foot syndrome, hypertension,

altered taste, nausea, dyspepsia, abdominal pain, hypothyroidism/TSH increased,

rash, hair color changes, anorexia, skin discoloration, constipation, vomiting,

bleeding events, epistaxis, and dysgeusia.

    For more information and full Prescribing Information, visit www.SUTENT.com

[http://www.SUTENT.com ].

    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 leading 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 - the company is everywhere. In 2017,

Merck generated sales of EUR 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.

    Pfizer Inc.: Working together for a healthier world(R)

    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

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    Pfizer Disclosure Notice

    The information contained in this release is as of February 11, 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 BAVENCIO

(avelumab), including a potential new indication for BAVENCIO in combination

with INLYTA (axitinib) for the treatment of patients with advanced renal cell

carcinoma, the alliance between Merck and Pfizer involving BAVENCIO 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 BAVENCIO; 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 further analyses of existing clinical data and

uncertainties regarding whether the other primary endpoint of JAVELIN Renal 101

will be met; 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 for BAVENCIO in combination with INLYTA for the

potential new indication in any other jurisdictions or in any jurisdictions for

any other potential indications for BAVENCIO or combination therapies; whether

and when the pending applications in the U.S. and Japan for BAVENCIO in

combination with INLYTA for the potential new indication may be approved and

whether and when regulatory authorities in any jurisdictions where any other

applications are pending or may be submitted for BAVENCIO or combination

therapies 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, manufacturing processes and/or other matters

that could affect the availability or commercial potential of BAVENCIO or

combination therapies, including BAVENCIO in combination with INLYTA for the

potential new 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, 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 www.sec.gov  and www.pfizer.com

    References

    1) National Cancer Institute: SEER Stat Fact Sheets: Kidney and renal

pelvis.       Available from: http://seer.cancer.gov/statfacts/html/kidrp.html.

Accessed February       2019.

     2) Ljungberg B, Campbell S and Cho H. The Epidemiology of Renal Cell

Carcinoma. Eur Urol.       2011;60:615-621.

     3) American Cancer Society. What is kidney cancer? Available from:       

https://www.cancer.org/cancer/kidney-cancer/about.html. Accessed February 2019.

    4) Escudier B, Porta C, Schmidinger M et al Renal cell carcinoma: ESMO

clinical practice guidelines for diagnosis, treatment and follow-up. Annal

Oncol. 2014; 25(Suppl3):iii49-iii56.

    5) American Cancer Society. Cancer facts and figures 2019. Available       

at:

https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2019/cancer-facts-and-figures-2019.pdf.

Accessed February 2019

     6) Dolan DE, Gupta S. PD-1 pathway inhibitors: changing the landscape of

cancer immunotherapy. Cancer Control. 2014;21(3):231-237.

     7) Dahan R, Sega E, Engelhardt J, Selby M, Korman AJ, Ravetch JV.

FcgammaRs modulate the anti-tumor activity of antibodies targeting the

PD-1/PD-L1 axis. Cancer Cell. 2015;28 (3):285-295.

     8) 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.

    9) Kohrt HE, Houot R, Marabelle A, et al. Combination strategies to enhance

antitumor ADCC. Immunotherapy. 2012;4(5):511-527.  

   10) Hamilton G, Rath B. Avelumab: combining immune checkpoint inhibition and

antibody-dependent cytotoxicity. Expert Opin Biol Ther. 2017;17(4):515-523.

    Merck:

    Media Relations: +49-151-1454-6328 friederike.segeberg@merckgroup.com

    Investor Relations: +49-6151-72-3321 investor.relations@merckgroup.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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Source:  Merck