Docket No.: CGR5001USCNT1
`
`I hereby certify that this correspondence is being transmitted Via The Office
`
`Electronic Filing System (EFS) in accordance with 37 CFR l.6(a)(4).
`
`Date of Electronic (EFS) Transmission:
`
`June 4, 2013
`
`Signature: /Laurie A. Phillips/ Name: Laurie A. Phillips
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`In re Application of:
`
`:4r>rii1i<i:i41nlt‘l(si)i3i
`§ApplicationNo.
`
`;_13/034,340
`
`5
`
`
`628
`
`_
`
`ii Title:
`
`Cancer
`
`Mail Stop Amendment
`Commissioner for Patents
`
`P.O. Box 1450
`
`Alexandria, VA 22313-1450
`
`Dear Sir:
`
`RESPONSE
`
`In response to the final Office Action mailed March 4, 2013, Applicant submits
`
`the following amendments and remarks.
`
`A list of the Claims are reflected in the listing of claims, which begins on page 2
`
`of this paper.
`
`Remarks/Arguments begin on page 4 of this paper.
`
`Page 1 of 9
`
`<T>1,16<END1>1<END2>14<END3>(594,-14)<E4>22</E4>0<E5>1<E6>18<E7>11<E8>12/1/2015 12:00:00 AM16:10:14.2084739<E9></T>
`
`

`
`Docket No.: CGR500 lUSCNTl
`
`Listing of Claims:
`
`1-36. (Canceled).
`
`37. (Previously presented) A method for the treatment of a prostate cancer in a human
`
`comprising administering to said human a therapeutically effective amount of abiraterone
`
`acetate or a pharrnaceutically acceptable salt thereof and a therapeutically effective
`
`amount of prednisone.
`
`38. (Previously presented) The method of claim 37, wherein the therapeutically effective
`
`amount of the abiraterone acetate or pharrnaceutically acceptable salt thereof is from
`
`about 50 mg/day to about 2000 mg/day.
`
`39. (Previously presented) The method of claim 38, wherein the therapeutically effective
`
`amount of the abiraterone acetate or pharrnaceutically acceptable salt thereof is from
`
`about 500 mg/day to about 1500 mg/day.
`
`40. (Previously presented) The method of claim 39, wherein the therapeutically effective
`
`amount of the abiraterone acetate or pharrnaceutically acceptable salt thereof is about
`
`1000 mg/day.
`
`Page 2 of 9
`
`

`
`Docket No.: CGR500 lUSCNTl
`
`41. (Previously presented) The method of claim 37, wherein the therapeutically effective
`
`amount of the abiraterone acetate or a pharrnaceutically acceptable salt
`
`thereof is
`
`administered in at least one dosage form comprising about 250 mg of abiraterone acetate
`
`or a pharrnaceutically acceptable salt thereof.
`
`42. (Previously presented) The method of claim 37, wherein the therapeutically effective
`
`amount of the prednisone is from about 0.01 mg/day to about 500 mg/day.
`
`43. (Previously presented) The method of claim 42, wherein the therapeutically effective
`
`amount of the prednisone is from about 10 mg/day to about 250 mg/day.
`
`44. (Previously presented) The method of claim 44, wherein the therapeutically effective
`
`amount of the prednisone is about 10 mg/day.
`
`45. (Previously presented) The method of claim 37, wherein the therapeutically effective
`
`amount of the prednisone is administered in at least one dosage form comprising about 5
`
`mg of prednisone.
`
`46. (Previously presented) The method of claim 37, comprising administering to said
`
`human about 500 mg/day to about 1500 mg/day of abiraterone acetate or
`
`a
`
`pharrnaceutically acceptable salt thereof and about 0.01 mg/day to about 500 mg/day of
`
`prednisone.
`
`Page 3 of 9
`
`

`
`Docket No.: CGR500 lUSCNTl
`
`47. (Previously presented) The method of claim 46, comprising administering to said
`
`human about l000 mg/day of abiraterone acetate or a pharrnaceutically acceptable salt
`
`thereof and about 10 mg/day of prednisone.
`
`48. (Previously presented) The method of claim 37, wherein said prostate cancer is
`
`refractory prostate cancer.
`
`49.
`
`(Previously presented) The method of claim 48, wherein the refractory prostate
`
`cancer is not responding to at least one anti-cancer agent.
`
`50. (Previously presented) The method of claim 49, wherein the at least one anti-cancer
`
`agent comprises a hormonal ablation agent, an anti-androgen agent, or an anti-neoplastic
`
`agent.
`
`51. (Previously presented) The method of claim 50, wherein the hormonal ablation agent
`
`comprises deslorelin, leuprolide, goserelin, or triptorelin.
`
`52. (Previously presented) The method of claim 50, wherein the anti-androgen agent
`
`comprises bicalutamide, flutamide, or nilutamide.
`
`53. (Previously presented) The method of claim 50, wherein the anti-neoplastic agent
`
`comprises docetaxel.
`
`Page 4 of 9
`
`

`
`Docket No.: CGR500 lUSCNTl
`
`54. (Previously presented) The method of claim 48, comprising administering to said
`
`human about 500 mg/day to about 1500 mg/day of abiraterone acetate or
`
`a
`
`pharrnaceutically acceptable salt thereof and about 0.01 mg/day to about 500 mg/day of
`
`prednisone.
`
`55. (Previously presented) The method of claim 54, comprising administering to said
`
`human about l000 mg/day of abiraterone acetate or a pharrnaceutically acceptable salt
`
`thereof and about 10 mg/day of prednisone.
`
`56. (Previously presented) The method of claim 53, comprising administering to said
`
`human about l000 mg/day of abiraterone acetate or a pharrnaceutically acceptable salt
`
`thereof and about 10 mg/day of prednisone.
`
`Page 5 of 9
`
`

`
`Docket No.: CGR500 lUSCNTl
`
`Remarks
`
`Claims 37-56 are pending.
`
`Re°ections Under 35 U.S.C.
`
`103
`
`The rejection of claims 37-56 under 35 USC §l03(a) as allegedly being
`
`unpatentable over O’Donell et al.
`
`(British Journal of Cancer 90:23l7-2325 (2004))
`
`(“O’Donell”), in view of Tannock et al. (Journal of Clinical Oncology 14:l756-1764
`
`(1996)) (Tannock”) was maintained. Applicant respectfully traverses this rejection.
`
`In Applicant’s previous reply, submitted January ll, 2013 (the “January Reply”),
`
`Applicant submitted the Ryan article. Ryan showed,
`
`inter alia,
`
`that
`
`the “median
`
`radiographic progression-free survival was l6.5 months with abiraterone-prednisone and
`
`8.3 months with prednisone alone .
`
`.
`
`. Radiographic progression-free survival was
`
`positively correlated with overall survival.” According to the Office,
`
`“the superior
`
`results of using abiraterone and prednisone together is expected because abiraterone and
`
`prednisone are known to be individually effective in treating prostate cancer. At least
`
`additive effective [sic]
`
`is expected.”
`
`However,
`
`the Office failed to provide any
`
`reasoning to support the expectation of at least an additive effect.
`
`In fact, the Off1ce’s
`
`own cited art is in opposition to the Off1ce’s statement that at least an additive effect is
`
`expected.
`
`Based on Tannock, the art cited by the Office, one of ordinary skill in the art
`
`would not expect at least an additive effect for overall survival of abiraterone and acetate
`
`and progesterone. Tannock teaches that “[t]here was no significant difference in overall
`
`survival
`
`[between prednisone
`
`alone
`
`and prednisone plus
`
`the
`
`anticancer
`
`agent
`
`mitoxantrone.]” One of ordinary skill in the art, reading Tannock, would expect there to
`
`be no difference in survival between one cancer agent alone, and that same cancer agent
`
`in combination with prednisone. Thus,
`
`the present invention possesses unexpected
`
`results and is non-obvious over the cited art.
`
`Further,
`
`the present
`
`invention has displayed commercial success. Applicant
`
`submits herewith the currently United States Food & Drug Administration approved label
`
`Page 6 of 9
`
`

`
`Docket No.: CGR5001USCNT1
`
`for ZYTIGATM (the “ZYTIGA label”). The ZYTIGA label indicates that “[abiraterone
`
`acetate] is a CYP17 inhibitor indicated in combination with prednisone for the treatment
`
`of patients with metastatic castration-resistant prostate cancer.” Taking ZYTIGA in
`
`accordance with the approved label represents a commercial embodiment of the presently
`
`claimed invention.
`
`Applicant also submits herewith a news release from the U.S. Food and Drug
`
`Administration dated December 10, 2012 and titled “FDA expands Zytiga’s use for late-
`9
`stage prostate cancer.’ As can be seen from this 2012 news release, ZYTIGA was
`
`initially approved in April 2011 for use in patients whose prostate cancer progressed after
`
`treatment with docetaxel, a chemotherapy drug. ZYTIGA was further approved in
`
`December 2012 for use in prostate cancer patients prior to receiving chemotherapy.
`
`Applicant also submits two further news releases from the U.S. Food and Drug
`
`Administration, one dated June 17, 2010, announcing approval of Jevtana for use in
`
`prostate cancer; and the other dated August 31, 2012, announcing the approval of Xtandi
`
`for use in patients whose prostate cancer progressed after treatment with docetaxel.
`
`Applicant also submits herewith “Pharmaceuticals Commericial Overview”, a
`
`slideshow presented by Joaquin Duato on May 23, 2013 and currently available at
`
`http://files.shareholder.com/downloads/JNJ/2514173625x0x666408/bb2972ea-2099-
`
`4ab4-b2a3 -afc3 9e7105 94/Pharrnaceutical_Commercial_Overview_JNJ20 1 3 .pdf
`
`(the
`
`“2013 slideshow”). According to the 2013 slideshow, at slide 11, ZYTIGA is the most
`
`successful oral oncology launch in history.
`
`The 2013 slideshow, at slide 12, further shows the July 2012 to April 2013
`
`ZYTIGA market share of chemo refractory prostate cancer patients, i.e., patients who
`
`have previously received chemotherapy treatment and the December 2012 to April 2013
`
`market share of chemo naive prostate cancer patients,
`
`i.e., patients who have not
`
`previously received chemotherapy treatment. As can be seen from the figure on the left
`
`of slide 12, ZYTIGA had almost 70% market share in July of 2012 for chemo refractory
`
`prostate cancer patients, just slightly over a year after ZYTIGA’s initial approval, and
`
`despite the fact that a JEVTANA had been approved two years earlier. Despite another
`
`product, XTANDI, being introduced in August of 2012, by April of 2013, ZYTIGA was
`
`Page 7 of 9
`
`

`
`Docket No.: CGR5001USCNT1
`
`still the market leader as of April 2013 with 57% market share in chemo refractory
`
`prostate cancer patients.
`
`As can be seen from the figure on the right of slide 12, shortly after its approval
`
`for chemo-naive patients in December 2012, ZYTIGA had a market share of 15%. As of
`
`April 2013, ZYTIGA’s market share was 20%, higher than two other available therapies,
`
`docetaxel and XTANDI, and approaching the market share of bicalutamide, a drug first
`
`approved in 2001 for prostate cancer.
`
`Thus, not only is ZYTIGA the most successful oral oncology launch in history,
`
`two years after its initial approval it is still the market leader for chemo refractory
`
`patients despite an earlier-introduced therapy and a later-introduced therapy. ZYTIGA
`
`also holds a strong market share in the chemo naive prostate cancer population, despite
`
`the presence of other marketed products. This commercial success demonstrates the non-
`
`obviousness of the presently claimed invention.
`
`Even assuming, arguendo, the cited art suggests the claimed combination, the
`
`present invention has shown surprising results, and commercial success. Thus, the claims
`
`are non-obvious over the cited art. Accordingly, Applicant requests reconsideration and
`
`withdrawal of the rejection under 35 USC §103(a).
`
`Page 8 of 9
`
`

`
`Docket No.: CGR500 lUSCNTl
`
`III. CONCLUSION
`
`Early consideration and prompt allowance of the claims are respectfully requested.
`
`Should the Office require anything further,
`
`it
`
`is
`
`invited to contact Applicant’s
`
`representative at the telephone number below.
`
`Applicant respectfully requests that a timely Notice of Allowance be issued in the
`
`present application. Should the Office require anything further, it is invited to contact
`
`Applicant’s representative at the telephone number below.
`
`JOHNSON & JOHNSON
`
`One Johnson & Johnson Plaza
`
`New Brunswick, NJ 08933-7003
`(732) 524-3957
`Dated: June 4, 2013
`Customer No.: 27777
`
`Respectfully submitted,
`
`/Andrea Jo Kamage/
`By:
`Andrea JO Kamage
`Reg. No. 43,703
`
`Page 9 of 9
`
`

`
`I hereby certify that this correspondence is being transmitted Via The Office
`
`Electronic Filing System (EFS) in accordance with 37 CFR 1.6(a)(4).
`
`Date of Electronic (EFS) Transmission:
`
`June 4, 2013
`
`Signature: /Laurie A. Phillips/ Name: Laurie A. Phillips
`
`IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
`
`In re Application of:
`
`§‘xg,5‘1;ga¢;5;ma‘I:‘
`
`
`
`
`onf.No.:
`
`% 1597
`
`
`‘f“Title:
`
`WIII55I'ikiéiiiéiigQiid’E6}iifi6§i{i6i{§i6f’r£ésitingIcéhééf
`
`Mail Stop Amendment
`Commissioner for Patents
`P.O. Box 1450
`
`Alexandria, VA 22313-1450
`
`NOTICE OF APPEAL
`
`Applicant hereby appeals to the Board of Patent Appeals and Interferences from the decision
`
`of the Examiner dated March 4, 2013 finally rejecting Claims 37-56 of the above-identified
`
`application.
`
`The item(s) checked below are appropriate:
`
`1.
`
`2.
`
`P’
`
`IZIIZIIIIIZIIZIIIIIII
`
`An extension of time to respond to the final rejection was granted on
`month(s).
`A Petition For Extension Of Time under 37 CFR 1.136 is attached hereto in
`
`for
`
`triplicate.
`A timely response to the final rejection has been filed.
`Fee $500.00: for filing of Notice of Appeal
`Not required (fee paid in prior appeal)
`Charge to Deposit Account No. 10-0750/AJK/CGR5001.
`The Commissioner is hereby authorized to charge any additional fees which may be
`required, or credit any overpayment in connection herewith to Deposit Account No.
`10-0750/AJK/CGR5001.
`
`Respectfully submitted,
`
`JOHNSON & JOHNSON
`One Johnson & Johnson Plaza
`
`New Brunswick, NJ 08933-7003
`(732) 524-3957
`Dated: June 4, 2013
`Customer No.: 27777
`
`/Andrea Jo Kamage/
`By:
`Andrea Jo Kamage
`Reg. No. 43,703
`
`

`
`S/4/13
`
`Press Announcements > FDA approves new treatment for 2: type of late stage ; rcetzate cancer
`
`
`
`~‘i'..
`
`.~
`
`‘s
`
`\\\\
`\
`
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`
`FEA NEWS RELEASE
`
`For Immediate Reiease: Aug. 31, 2012
`Media Enquiries: Erica Jefferson, 301—796~4Ei88,
`flonsumer Enquiries: 88i'5~Ii\iFD—FDA
`
`41
`
`
`
`sea approves new treatment for a type of iate stage prostate cancer
`
`The US. Food and Drug Administration today approved Xtandi ijenzaiutamide) to treat men with iate—stage
`(metastatic) castration~resistant prostate cancer that has spread or recurred, even with medicai or surgicz
`therapy to minimize testosterone.
`
`Approved for prostate cancer patients previousiy treated with docetaxei, another anti—cancer treatment,
`Xtandi was reviewed under the FDA’s priority review program. The program provides for an expedited si><~
`in:-nth review for drugs that may offer major advances in treatment or that provide a treatment when no
`adequate therapy exists. Xtandi received Fill-A approvai three months ahead of the product's prescription
`drug user fee goai date of Nov. 22, 2012,
`
`“The need for additic-nai treatment options for advanced prostate cancer continues to be important for
`patients,” said Richard Pazdur, ii/i.[)., director of the Ciffice of riematoiogy and Oncoiogy Products in FDA’s
`Center for Drug Evaiuation and Research. “Xtandi is the iatest treatment for this disease to demonstrate its
`ahiiity to extend a patient’s iife.”
`
`Prostate cancer forms in a giand in the maie reproductive system found heic-w the hiadder and in front of
`the rectum. The maie sex hormone test-3-sterone stirnuiates the prostate tumors to grow. According to the
`Natic-nai Cancer institute, an estimated 241,74-C: men wiii he diagnosed with prc-state cancer and 28,173 wii
`die from the disease in 2012.
`
`The safety and effe<;t'iveness oi’ Xrtandi was evaiuated in a study of 1,199 patients with metastatic
`castration~ resistant prostate cancer who had received prior treatment with dc-cetaxei. The study was
`designed to measure -3-veraii survivai (the iength of tirne hefore death) in men receiving Xtandi compared
`with men receiving a piaceho {sugar piii). The median -3-veraii survivai for patients receiving Xtandi was 18.4
`months, cornpared with 13.6 months for the patients who received piaceho.
`
`The roost common side effergrts observed in study participants taking Xtandi were weaizness or fatigue, haci
`pain, diarrhea, joint pain, hot "flush, tissue sweiiing, rnuscuiosi<.eie'tai pain, headache, upper respiratory
`infections, dizziness, spihai cord compression and cauda equina syndrome, nriuscuiar weaitness, difficuity
`sieeping,
`ic-wer respiratory infections, biood in urine, tirigiihg sensation, anxiety, and high hiood pressure.
`
`Seizures occurred in a;:.=pro><irriateiv 1 percent of those receiving Xtandi. Patients in the study who had a
`seizure stopped Xtandi therapy. The ciinicai study exciuded patients with a history of seizure, an urideriving
`brain injury with ioss of consciousness, a ternporary decrease in hiood to the hrain within the past 12
`months, a stroke, hrain metastases, an ahnorrnai connection of the arteries and veins in the brain, or
`patients tai<irig n":edications that may iower the seizure threshoid. The safety of Xiiandi is unknown in
`patients with these conditions.
`
`Xrtandi wiii be co» mari<eted by Asteiias Pharrna iJ.E§., Inc. of Noriihhrook, ii. and iviedivation, inc. of San
`Francisco, CA.
`
`For more information:
`-_.
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`FDA, an agency within the U.S. Department of Heaith and Hurnan Services, protects the puhiic heaith by
`assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other
`hi-3-iogicai products for human use, and medicai devices. The agency aiso is responsihie for the safety and
`security of our nation's food suppiy, cosmetics, dietary suppiements, products that give off eiectrc-nic
`radiation, and for reguiating tobacco products.
`
`#
`
`www.fda.g ov/N ews Events/i\= ems room’PressAnnouncements,/ucrnz‘":
`
`him
`
`1,/2
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`

`
`S/4/13
`
`Press Announcements > FDA approves new treatment for 2: type of late stage prc:-stzatez cancer
`
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`v.w.v.fda.g ov/N ews Events/N ems room/PressAnnouncements,/ucm;":
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`him
`
`

`
`5/4/13
`
`Prses Announcements > FDA Approves New Treatment for Advanced Prostate Cancer
`
`
`
`Archived Content
`
`The content on this page is provided for reference purposes oniy, It was current when
`produced, hot is no ionger maintained and may he outdated,
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`////
`
`EBA NEWS RELEASE
`
`For immediate heiease: June 17', 201:’)
`Media Enquiries: Erica Jefferson, 3t'i1~796- 4988,
`Consumer Enquiries: 888~Ii\iFO—FDA
`
`Foe, approves New “treatment for advanced Prostate Eancer
`
`The U5. Food and Drug Administration today approved Jevtana {cahazitaxei}, a chemotherapy drug used ir
`combination with the steroici prednisone to treat men with prostate cancer, Jevtana is the first treatment
`for advanced, hormone—i'etractory, prostate cancer that has worsened during or after treatment with
`docetaxei, a commoniv used drug for advanced prostate cancer,
`
`In prostate cancer, the maie sex, hormone testosterone can cause prostate tumors to grow, Drugs, surgery
`or other hormones are used to reduce testosterone production or to biock it, Some men have hormone
`refractory prostate cancer, meaning the prostate cancer ceiis contincie to grow, despite testosterone
`suppression. Different treatments are needed for men with this type of cancer,
`
`Jevtana was reviewed under the FDA’s priority review program, which provides for an expedited si><~ month
`review for drugs that may offer major advances in treatment, or provide a treatment when no adequate
`therapy exists, Jevtana received approvai ahead of the product's Sept, 30, 2010, goai date,
`
`“Patients have few therapeutic options in this disease setting,” said Richard Pazdur, EVLEI-,, director of the
`Cfittice of =.".)ncoiogy Drug Products, part of the FDA’s Center for Drug Evaitiation and Research. “FDA was
`ahie to review and approve the appiication for Jevtana in 11 weeks, expediting the avaiiahiiity of this drug
`to men with prostate cancer,”
`
`Jievtana’s safety and effectiveness was esitabiished in a singie, 7S5~patient study. Aii study participants
`had previousiy received docetaxei. The study was designed to
`overaii stirvivai {the iength of time
`before death) in men who received Jievtana in cornhinatirm with prednisone compared with those who
`received the chemotherapy drug, mitoxantrone, in combination with prednisone. The median overaii survivai
`for patients receiving the Jevtana regimen was 15,1 months compared with 12.7 months for those who
`received the mitoxantrone regimen.
`
`Side effects in those treated with Jevtana incidded decrease in infer_:ition-fighiiing white hiood ceiis
`(neoitropenia), anemia, decrease in the number of white hiood ceiis (ieukopenia), iow ievei of oiaiieieiis in th
`hiood (thromhocvtopenia), diarrhea, fatigue, nausea, vomiting, constipat.ion, weakness (asthenia), and renz
`taiiure.
`
`is the second most common cancer among men in the
`Prostate cancer, which usuaiiv occurs in oider men,
`Linited States, hehind skin cancer. in .3?.s’_‘;iJ6, the most. recent year for which numbers were avaiiabie,
`.?~?.ti3,4:i5 men deveioped prostate cancer and 28,372. men died from the disease, accortiing; to the Centers
`for
`Controi and iirevention.
`
`.ievtana is marketed iay ifiridgewaiier, N.3.~hased Sanofiwfivenitis.
`For more information:
`N“ in
`5
`:_.?.~'—~,.
`
`®
`
`.,
`
`‘
`
`‘: L:
`
`
`
`wwvv.fda.g ov/News Events/i\=emsroom/PressAnnouncernents/ucrn2'i 614.3.htm
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`Prams; Annczunce
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`
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`I2. nttp:,’jwvxn:»ucdc.geyvfcancer!prostate/informe::i____decision___maE«:ing,htm
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`S/4/13
`
`Press Announcements > FDA expands Zgnigas use for |ete~st2age prostate cancer
`
`
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`
`FEA NEWS RELEASE
`
`For Immediate Reiease: Dec. 10, 2012
`Media Enquiries: Stephanie Yao, 3€)1—796~0394,
`flnnsumer Enquiries: 88f5~ii\.iFD—FDA
`
`
`
`spa expands Zytigae use for iate-stage prostate cancer
`Drug can now be used before treatment with chemothera,oy
`
`The US, Footi and Drug Administration today e)-zpantied the approved use of Zytiga {ahiraterone acetate)
`to treat men with iate~stage (metastatic) CEiSti'€iti0Fi“i'€SiSt&i’it
`prostate cancer prior to re<:ei’v‘ing
`chemotherapy.
`
`The FDA initiaiiy approved Zytiga in Aprii 2011 for use in patients whose prostate cancer progressed after
`treatment with docetaxei, a chernotherapy drug. Zytiga is a piii that decreases the production of rnaie Se)-:
`hormone testosterone..
`
`In prostate cancer, testosterone stirnuiates prostate tumors to grow. Drugs or surgery are used to reciuce
`testosterone production or to hiocia testosterone’s effects. Some men have castration—resistaht prostate
`cancer, meaning the prostate cancer ceiis continue to grow even with iow ieveis of testosterone,
`
`“Today's approyai demonstrates the oenefit of further evaiuating a -zirug in an eariier disease setting an-at
`provides patients and heaith care providers the option of using Zytiga eariier in the course of treatment,”
`said Richar-zi Pazdur, iVi,D., -ziirector of the Office of Cincoiogy Drug Pr-3-tiiicts in the FDA’s Center for Drug
`Evaiiiation and Research.
`
`The FDA reviewed Zy'tiga’s appiication for this new indication under the agen:;y’s priority review program.
`The program provides for an expedited si:<—month review for drugs that may offer major advances in
`treatment or provide a trea'tm.ent when no adequate therapy exists.
`
`t_:iinit_:ai study of 1,€.i88 men
`Zyti<_.;a’s safety and effectiveness for its expanded use were estahiisheo in
`with iate~stage, cast.ration—resistant prostate cancer who had not preyiousiy received chemotherapy.
`Participants received either Zytiga or
`piaceho (sugar piii) in combination with prednisone.
`
`The study was ciesigneci to measure the iehgth of time a patient iived before death ifoveraii survivai} and
`the iength of time a patient iived without further turner growth
`assessed by imaging studies (radiographi
`progression-"free survivai, or rPFS).
`
`Patients who i'e€;eived Zytiga had a median overaii survivai of 35.3 months compareci with 30.1 months. for
`those re<:eiving the piaceho. Study resuits aiso showed Zytiga impro'v‘ee;i rPFS. The median ri>FS was 8.3
`months. in the piaoepo group and had not yet heen rear;hed for patients treated with Zytiga at the time of
`anaiysis.
`
`The most common side effects. reported in those receiving Zytiga irmiude fatigue, joint sweiiing or
`discorrifort, sweiiing caused hy fiuid retention, hot tiiish, diarrhea, vomiting, cough, high hiood pressure,
`shortness of breath, urinary‘ tract infection, and hruisirig.
`
`The most common iahorat-3-ry ahnormaiities ihcititied iow red hiood ceii count; high ieveis of the enzyme
`aikaiine phosphatase, which can he a sign of other serious mdicai protriemsg high ieyeis of fatty acids,
`sugar, and iiver enzymes in the hiooci; anti iow ieyeis of iympho<:ytes_, phosphorous anti potassium in the
`hiooci.
`
`Zytiga is marketed hy itorsham, Pa,~haseo Janssen Si-3-tech Inc.
`For more information:
`
`
`
`this press reiease was updated on See. so, Bot? at 2:39 am. to correct the date when zytiga was
`
`vwwv.fo'a.g ov/N ewe Events/N ems room’PressAnnouncements/ucm33 1 492. him
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`5/4/13
`
`Press Anric:-uncements > FDA eiqaancis Zgnigas use for Ieatestzage prostate czzancer
`
`eriginaiiy apprevea’ ta Aprii 2321.
`
`The FDA, an agency within the 3.1.8. Department of Health and Human Services, protects the pubiic neaitii
`by asstiring the safety, effectiveness, and SeCi.ii'i’=C‘;i of human and veterinary‘ drugs, vac-zines an-zi other
`bi-3-Eogi-zai we-ziucts for human use, an-zi medicai devices. The agency aiso is respehsibie for the safety and
`security of our nations fcrod supply, cosmetics, dietary suppienients, prociu-cts that give off eiectr-3-nit:
`radiati-3-n_, and for regtiiating tcxbacccr products,
`
`Read our Biogz Fm’-X Voiceg
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`,
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`Feed for FVDA ixews iiieieasesll
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`Page Last Up-ziate-2i: 12;'1Ci,/2012
`Note: if you need iieip accessing Entoranation in -ziiffereait fiie formats, see
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`U.S». Food arid Drug I-idministra'tion
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`Ph. 1-888-If\iFfJ-FDA (1-888~463—6332)
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`
`
`Links an this page:
`1.
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`,/AbeutFiifixjfjentersOFfices;’C}FFiceofMedi<;aiProtjuctsandTot>acr_:ojCi3ER,fii<;m091745.iitrn
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`,fDrugs;’ResourcesForYoii,r’Censurners,»’ucmiJS4420.htrn
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`«ii,
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`titt:3:/iwww.cancer.gcsv/caneertopics,r’types;'prostate
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`5. https:f,/biogs.fda,gov/fa:iaveice,r’
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`6
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`7
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`titt:3:/hwiw.facebooi<.cem.’FDA
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`iittgaz/;’wiA;w.fii-2kitcom,/pnotosftdaphotos,’
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`10, http:;’,"‘.«iww.fcia.g«:2v,»’Ai:s<:rutFDA/AboutThisV‘.’ebsitefV1iebsitePoEiciesffiisciairneisfdefauit,htm
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`11, http:;’,"‘.w:w.fcia,g«:>v;’Ai:i<:rutFDA,"Conta<:tFDAfStayInf«3rmedfRESFeeds,/PressReieasesirss..><anE
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`
`i'ilGi-li.iGi'iT:‘.§ SF P§iE:‘.§{2§‘ilE3ii\ifi il\iF{3l'~iMATiDi\l
`
`These highlights do nnt include all the infermatinn needed to use ZVTEEA safely
`and effectively. See full prescribing inierrnation lo: ZYTEGA.
`
`ZY'E'EGA®
`iahirateione acetate} Tablets
`
`For Dral Adaninis‘-lration
`
`initial D.S. Approval w 2D'i‘l
`
`REQENT gyqmgg
`
`indications and usage it‘;
`Contraindications, Pregnancy i4~.li
`Warnings and Precautions. Mineraiocorticoirl excess (iii)
`Warriings and Precautions, Adreriocoitical lnsul'iiciency (5.2;
`Warnings and Precautions, liepatotoxicity (5.3)
`
`§N{}§(;AT§fiNS Am)
`
`..
`
`‘-2,/'_£‘.-l2
`i2,/2t'll2
`T2/2012
`i2/2012
`i2/'2Eil2
`
`inhibitor indicated in combination with prednisone tor the
`ZY'l'lGA is a CYPEE’
`treatment of patients with metastatic r;astration—resistant prostate cancer. ill
`
`-----------------------------—-DOSAGE AND AE)iVllNiSTRATi0i\l
`
`Recommended dose: ZYTEGA l_.OCIt'l mg (four 250 mg tablets) adrninistered orally
`once daily in combination with prednisone El mg administered orally twice daily.
`ZYTlGA mast
`taken on an empty stomach. No food should he consumed for at
`least two hours before the dose of ZYTlGA is taken and for at ieest one noirr
`after the dose of Z‘r"liG.i\ is taken. The tablets should
`swaliewed whole with
`water. [lo riot crush or chew tablets. (2.l)
`-o For patients with baseline moderate hepatic impairment (Child-Pugh Class Bi,
`reduce the Z‘r"TiG/»\ starting dose to 250 mg once daily. (2.2)
`as For patients who develop hepatotoxicity during treatment, hold Z‘{liT5A until
`recovery. Retreatrnent may be initiated at a reduced dose. ZYTEGA should be
`discontinued if patients develop severe hepatotoxicity. (2.2)
`
`---------------------------~- DD§A£§E Fmtltilizi AND STREi\iG"i'li$-~-~--~--~--~--~--~--~--~-
`:51
`Tablet 2 0 mg (3)
`
`CQMTRpJ§\§[)§f;A‘§'iQN5...................................................
`
`-o Z‘Y"liGA is contrrnnrlicateri
`\
`1
`.
`-'4-.1 8.1)
`
`in women who are or may become pregnant.
`
`ZY'i'lGA® la iiirallemne acetate} Ta islets
`
`———————————————————————————--WARi\iii’\lG5 Ans Pi§EE3AD'i'i{3NS»--~--~--~--~--~-~~-~--~--~--
`
`as
`
`iviiheraiocorticoid excess: ilse Z’YTlGA with cairtion in patients with a histony
`of cardiovascular disease. The safety or‘ Z‘rTiGA in patients with i.‘\/El‘ < 50% or
`i\i‘{il/‘t Class ill or iv’ heart failure in Study l or LVEF < 50 % or l\i\{HA Class ii
`to EV heart failure in Study 2 was not estaiaiished. Control hypertension
`correct
`iiypokaiemia before treatment.
`lvlonitor blood pressure,
`serum
`potassium and symptoms of fluid retention at ieast monthiy. (5.1)
`
`or‘
`signs
`a Adrenocorticai
`insufficiency: Monitor
`for
`syrnpt-.
`is
`and
`adrenocorticai
`insufficiency.
`increased dosage of corticosteroids may be
`indicated before, tilJl'iT‘.t] and after stressful situations. (5.2)
`6 ileoatotoxicity: increases in liver enzyrnes have
`to drug interruption, dose
`rnodilication and/or discontinuation.
`lvlonitor
`liver
`function and modify,
`interrupt, or discontinue ZYTEGA dosing as recommended. i5.3i
`a Food effect: Z‘r’l'ii_-TA must be taken on an empty stomach. Exposure (area
`under the curve) of abireterone increases up to it) told when abiraterone
`acetate is taken with meats. i5./ii
`——————————————————————————————————- ADVERSE REACTEDNS~--—-~—-~--~~--~-----—-~--—--—-~--~
`
`joint swelling or
`The most common adverse reactions (2 lO%_l are tatigue,
`discomfort, edema, not flush, diarrhea, vomiting, cough, hypertension, dyspnea,
`arinarytrattt infection and contusion.
`
`The most common laboratory a"onormaiities i> 20%) are anemia, elevated alkaline
`phosphatase, hypertrigly-seridemia,
`lymphopenia, hyperchelester-:-lemia, hyper-
`glycemia, eievated AST, hypophosphatemia, elevated ALT and hypoi<alemia. (6)
`
`SEJSDEEZTED ADVERSE REACTEDNS, contact
`regmrt
`To
`at
`i-8&3--526--3735
`ii--Bill}-JANSSENE or
`FDA at
`ins.
`www.fd‘a.gov/nzedwatch.
`----------------------------------- Billifi ENTEFEADTEGNS
`
`tinnssen Biotech,
`’l--Bill}-FDA-v’l(}38