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` UNITED STATES DISTRICT COURT
`DISTRICT OF NEW JERSEY
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`PATRICIA JONES,
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`Plaintiff,
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`vs.
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`JANSSEN PHARMACEUTICALS, INC. f/k/a
`JANSSEN PHARMACEUTICA INC. f/k/a
`ORTHO-MCNEIL-JANSSEN PHARMACEUTICALS, INC.;
`JANSSEN ORTHO LLC;
`JANSSEN RESEARCH & DEVELOPMENT LLC f/k/a
`JOHNSON AND JOHNSON PHARMACEUTICAL
`RESEARCH AND DEVELOPMENT LLC;
`ORTHO-MCNEIL PHARMACEUTICALS, LLC;
`JOHNSON & JOHNSON COMPANY;
`TEVA BRANDED PHARMACEUTICAL PRODUCTS
`R&D, INC.; and TEVA PHARMACEUTICALS USA, INC.
`
`
`Defendants.
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`Civil Action No.:
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`COMPLAINT
`AND DEMAND
`FOR JURY TRIAL
`
`Plaintiff, by her attorneys, DOUGLAS & LONDON, P.C., upon information and belief, at all times
`
`hereinafter mentioned, allege as follows:
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`
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`JURISDICTION AND VENUE
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`1.
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`This Court has jurisdiction over this action pursuant to 28 U.S.C. § 1332, because the amount
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`in controversy as to the Plaintiff exceeds $75,000.00, exclusive of interest and costs, and because
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`Defendants have their principal places of business in New Jersey rather than the state in which the named
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`Plaintiff resides.
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`1
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`Case 3:20-cv-14909-BRM-ZNQ Document 1 Filed 10/23/20 Page 2 of 58 PageID: 2
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`2.
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`This Court has personal jurisdiction over Defendants consistent with the United States
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`Constitution as Plaintiff’s claims arise out of Defendants’ transaction of business and the tortuous acts
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`within the State of New Jersey, and by virtue of Defendants’ substantial, continuous, and systematic
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`contacts with the State of New Jersey unrelated to Plaintiff’s claims.
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`
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`NATURE OF THE CASE
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`3.
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`This is an action for damages suffered by Plaintiff as a direct and proximate result of
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`Defendants' negligent and wrongful conduct in connection with the design, development, manufacture,
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`testing, packaging, promoting, marketing, distribution, labeling, and/or sale of ELMIRON for the relief of
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`bladder pain or discomfort associated with interstitial cystitis.
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`4.
`
`Defendants
`
`JANSSEN
`
`PHARMACEUTICALS,
`
`INC.
`
`f/k/a
`
`JANSSEN
`
`PHARMACEUTICA INC. f/k/a ORTHO-MCNEIL-JANSSEN PHARMACEUTICALS, INC.; JANSSEN
`
`ORTHO LLC; JANSSEN RESEARCH & DEVELOPMENT LLC f/k/a JOHNSON AND JOHNSON
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`PHARMACEUTICAL RESEARCH AND DEVELOPMENT LLC; JOHNSON & JOHNSON
`
`COMPANY;
`
`ORTHO-MCNEIL
`
`PHARMACEUTICALS,
`
`LLC;
`
`TEVA
`
`BRANDED
`
`PHARMACEUTICAL PRODUCTS R&D, INC.; and TEVA PHARMACEUTICALS USA, INC.
`
`(hereinafter collectively referred to as “Defendants”) concealed, and continue to conceal, their knowledge
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`of ELMIRON’s unreasonably dangerous risks from Plaintiff, other consumers, and the medical community.
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`5.
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`As a result of the defective nature of ELMIRON, persons who were prescribed and ingested
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`ELMIRON, including Plaintiff PATRICIA JONES has suffered and may continue to suffer severe and
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`permanent personal injuries, including but not limited to retinal pigmentary changes, vision changes, and
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`potentially irreversible vision damage.
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`6.
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`After beginning treatment with ELMIRON, and as a direct and proximate result of
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`Defendants’ actions and inaction, Plaintiff PATRICIA JONES suffered retinal pigmentary changes,
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`
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`2
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`Case 3:20-cv-14909-BRM-ZNQ Document 1 Filed 10/23/20 Page 3 of 58 PageID: 3
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`including macular degeneration. Plaintiff PATRICIA JONES’S ingestion of the defective and unreasonably
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`dangerous drug ELMIRON has caused and will continue to cause injury and damage to Plaintiff.
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`7.
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`Plaintiff brings this action for personal injuries suffered as a proximate result of Plaintiff
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`PATRICIA JONES being prescribed and ingesting ELMIRON. Plaintiff accordingly seeks compensatory
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`and punitive damages, monetary restitution, and all other available remedies as a result of injuries caused
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`by ELMIRON.
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`PARTY PLAINTIFF
`
`8.
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`9.
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`10.
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`11.
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`Plaintiff PATRICIA JONES is a citizen and resident of the State of North Carolina.
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`Plaintiff PATRICIA JONES was born on November 9, 1958.
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`Plaintiff PATRICIA JONES began taking ELMIRON in or about 1998.
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`As result of using Defendants’ ELMIRON, Plaintiff PATRICIA JONES, was caused to
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`suffer retinal pigmentary changes, including macular degeneration on or about October 13, 2020.
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`12.
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`As a result of using Defendants’ ELMIRON, Plaintiff was caused to sustain severe and
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`permanent personal injuries, pain, suffering, and emotional distress.
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`13.
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`The injuries and damages sustained by Plaintiff was caused by Defendants’ ELMIRON.
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`
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`PARTY DEFENDANTS
`
`14.
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`Upon information and belief, Defendant JANSSEN PHARMACEUTICALS, INC. f/k/a
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`JANSSEN PHARMACEUTICA INC. f/k/a ORTHO-MCNEIL-JANSSEN PHARMACEUTICALS, INC.
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`(hereinafter referred to as “JANSSEN PHARM”) is a Pennsylvania corporation, having a principal place of
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`business at 1125 Trenton-Harbourton Road, Titusville, New Jersey 08560, and is a wholly owned subsidiary
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`of Defendant JOHNSON & JOHNSON COMPANY.
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`15.
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`As part of its business, Defendant JANSSEN PHARM is involved in the research,
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`development, design, licensing, manufacture, distribution, supply, sales and/or marketing, and introduction
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`
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`3
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`Case 3:20-cv-14909-BRM-ZNQ Document 1 Filed 10/23/20 Page 4 of 58 PageID: 4
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`into interstate commerce, either directly or indirectly through third parties or related entities, of
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`pharmaceutical products including ELMIRON and pentosan polysulfate sodium.
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`16.
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`Upon information and belief, Defendant JANSSEN PHARM has transacted and conducted
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`business in the State of New Jersey and the State of North Carolina.
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`17.
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`Upon information and belief, Defendant JANSSEN PHARM, has derived substantial
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`revenue from goods and products used in the State of New Jersey and the State of North Carolina.
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`18.
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`Upon information and belief, Defendant JANSSEN PHARM expected or should have
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`expected its acts to have consequence within the United States of America and the State of New Jersey and
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`the State of North Carolina, and derived substantial revenue from interstate commerce within the United
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`States and the State of New Jersey and the State of North Carolina, more particularly.
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`19.
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`Upon information and belief, and at all relevant times, Defendant JANSSEN PHARM was
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`in the business of and did design, research, manufacture, test, advertise, promote, market, sell, and distribute
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`the drug ELMIRON for the relief of bladder pain or discomfort associated with interstitial cystitis.
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`20.
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`Upon information and belief, Defendant JANSSEN ORTHO LLC (hereinafter referred to as
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`“JANSSEN ORTHO”) is a limited liability company organized under the laws of Delaware, having a
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`principal place of business at Stateroad 933 Km 0 1, Street Statero, Gurabo, Puerto Rico 00778. Defendant
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`JANSSEN ORTHO is a subsidiary of Johnson & Johnson.
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`21.
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`As part of its business, Defendant JANSSEN ORTHO is involved in the research,
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`development, sales, and marketing of pharmaceutical products including ELMIRON and pentosan
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`polysulfate sodium.
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`22.
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`Upon information and belief, Defendant JANSSEN ORTHO has transacted and conducted
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`business in the State of New Jersey and the State of North Carolina.
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`4
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`23.
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`Upon information and belief, Defendant JANSSEN ORTHO has derived substantial revenue
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`from goods and products used in the State of New Jersey and the State of North Carolina.
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`24.
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`Upon information and belief, Defendant JANSSEN ORTHO expected or should have
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`expected its acts to have consequence within the United States of America and the State of New Jersey and
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`the State of North Carolina, and derived substantial revenue from interstate commerce within the United
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`States and the State of New Jersey and the State of North Carolina, more particularly.
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`25.
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`Upon information and belief, and at all relevant times, Defendant JANSSEN ORTHO was
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`in the business of and did design, research, manufacture, test, advertise, promote, market, sell, and distribute
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`the drug ELMIRON for the relief of bladder pain or discomfort associated with interstitial cystitis.
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`26.
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`Upon information and belief, Defendant JANSSEN RESEARCH & DEVELOPMENT LLC
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`f/k/a JOHNSON AND JOHNSON RESEARCH AND DEVELOPMENT LLC (hereinafter referred to as
`
`“JANSSEN R&D”) is a limited liability company organized under the laws of New Jersey, with a principal
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`place of business at One Johnson & Johnson Plaza, New Brunswick, Middlesex County, New Jersey 08933.
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`Defendant JANSSEN R&D’s sole member is Centocor Research & Development, Inc., which is a
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`Pennsylvania corporation with a principal place of business in Pennsylvania. Accordingly, JANSSEN R&D
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`is a citizen of Pennsylvania and New Jersey for purposes of determining diversity under 28 U.S.C. § 1332.
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`27.
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`Upon information and belief, Defendant JANSSEN R&D has transacted and conducted
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`business in the State of New Jersey and the State of North Carolina.
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`28.
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`Upon information and belief, Defendant JANSSEN R&D has derived substantial revenue
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`from good and products used in the State of New Jersey and the State of North Carolina.
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`29.
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`Upon information and belief, Defendant JANSSEN R&D expected or should have expected
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`its acts to have consequence within the United States of America and the State of New Jersey and the State
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`5
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`of North Carolina, and derived substantial revenue from interstate commerce within the United States and
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`the State of New Jersey and the State of North Carolina, more particularly.
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`30.
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`Upon information and belief, and at all relevant times, Defendant JANSSEN R&D was in
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`the business of and did design, research, manufacture, test, advertise, promote, market, sell, and distribute
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`the drug ELMIRON for the relief of bladder pain or discomfort associated with interstitial cystitis.
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`31.
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`Upon information and belief, Defendant ORTHO-MCNEIL PHARMACEUTICALS, INC.
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`(hereinafter referred to as “ORTHO PHARMA”) is a corporation organized under the laws of Delaware
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`with its principal place of business at 1000 US Highway 202, Raritan, New Jersey 08869, and is a wholly
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`owned subsidiary of Defendant JOHNSON & JOHNSON COMPANY.
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`32.
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`Upon information and belief, Defendant ORTHO PHARMA has transacted and conducted
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`business in the State of New Jersey and the State of North Carolina.
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`33.
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`Upon information and belief, Defendant ORTHO PHARMA has derived substantial revenue
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`from good and products used in the State of New Jersey and the State of North Carolina.
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`34.
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`Upon information and belief, Defendant ORTHO PHARMA expected or should have
`
`expected its acts to have consequence within the United States of America and the State of New Jersey and
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`the State of North Carolina, and derived substantial revenue from interstate commerce within the United
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`States and the State of New Jersey and the State of North Carolina, more particularly.
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`35.
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`Upon information and belief, and at all relevant times, Defendant ORTHO PHARMA was
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`in the business of and did design, research, manufacture, test, advertise, promote, market, sell, and distribute
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`the drug ELMIRON for the relief of bladder pain or discomfort associated with interstitial cystitis.
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`36.
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`Upon information and belief, Defendant JOHNSON & JOHNSON COMPANY (hereinafter
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`referred to as “J&J”) is a corporation organized under the laws of New Jersey with its principal place of
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`business at One Johnson & Johnson Plaza, New Brunswick, Middlesex County, New Jersey 08933.
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`6
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`37.
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`Upon information and belief, and at all relevant times, Defendants JANSSEN PHARM,
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`ORTHO PHARMA, and JANSSEN R&D are wholly owned subsidiaries of Defendant J&J.
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`38.
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`As part of its business, Defendant J&J is and at all relevant times was, involved in the
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`research, development, design, licensing, manufacture, distribution, supply, packaging, labeling, sales,
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`and/or marketing and introduction into interstate commerce, either directly or indirectly through third
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`parties or related entities, of pharmaceutical products including ELMIRON. Defendant J&J manufactures,
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`markets, and sells a wide range of pharmaceutical products including ELMIRON and pentosan polysuflate
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`sodium.
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`39.
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`Upon information and belief, Defendant J&J has transacted and conducted business in the
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`State of New Jersey and North Carolina.
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`40.
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`Upon information and belief, Defendant J&J has derived substantial revenue from goods and
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`products used in the State of New Jersey and the State of North Carolina.
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`41.
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`Upon information and belief, Defendant J&J expected or should have expected its acts to
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`have consequence within the United States of America and the State of New Jersey and the State North
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`Carolina, and derived substantial revenue from interstate commerce within the United States and the State
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`of New Jersey and the State of North Carolina, more particularly.
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`42.
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`Upon information and belief, and at all relevant times, Defendant J&J was in the business of
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`and did design, research, manufacture, test, advertise, promote, market, sell, and distribute the drug
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`ELMIRON for the relief of bladder pain or discomfort associated with interstitial cystitis.
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`43.
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`Upon information and belief, Defendant TEVA BRANDED PHARMACEUTICAL
`
`PRODUCTS R&D, INC. (hereinafter referred to as “TEVA R&D”) is a corporation organized under the
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`laws of Delaware, having a principal place of business at 41 Moores Road, Frazer, Pennsylvania 19355.
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`7
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`44.
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`As part of its business, Defendant TEVA R&D is involved in the research, development,
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`sales, and marketing of pharmaceutical products including ELMIRON and pentosan polysulfate sodium.
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`45.
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`Upon information and belief, Defendant TEVA R&D has transacted and conducted business
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`in the State of New Jersey and the State of North Carolina.
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`46.
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`Upon information and belief, Defendant TEVA R&D has derived substantial revenue from
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`goods and products used in the State of New Jersey and the State of North Carolina.
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`47.
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`Upon information and belief, Defendant TEVA R&D expected or should have expected its
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`acts to have consequence within the United States of America and the State of New Jersey and the State of
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`North Carolina, and derived substantial revenue from interstate commerce within the United States and the
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`State of New Jersey and the State of North Carolina, more particularly.
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`48.
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`Upon information and belief, and at all relevant times, Defendant TEVA R&D was in the
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`business of and did design, research, manufacture, test, advertise, promote, market, sell, and distribute the
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`drug ELMIRON for the relief of bladder pain or discomfort associated with interstitial cystitis.
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`49.
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`Upon information and belief, Defendant TEVA PHARMACEUTICALS USA, INC.
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`(hereinafter referred to as “TEVA USA”) is a corporation organized under the laws of Delaware, having a
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`principal place of business at 400 Interpace Parkway, Parsippany, NJ 07054.
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`50.
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`As part of its business, Defendant TEVA USA is involved in the research, development,
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`sales, and marketing of pharmaceutical products including ELMIRON and pentosan polysulfate sodium.
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`51.
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`Upon information and belief, Defendant TEVA USA has transacted and conducted business
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`in the State of New Jersey and the State of North Carolina.
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`52.
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`Upon information and belief, Defendant TEVA USA has derived substantial revenue from
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`goods and products used in the State of New Jersey and the State of North Carolina.
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`8
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`53.
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`Upon information and belief, Defendant TEVA USA expected or should have expected its
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`acts to have consequence within the United States of America and the State of New Jersey and the State of
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`North Carolina, and derived substantial revenue from interstate commerce within the United States and the
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`State of New Jersey and the State of North Carolina, more particularly.
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`54.
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`Upon information and belief, and at all relevant times, Defendant TEVA USA was in the
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`business of and did design, research, manufacture, test, advertise, promote, market, sell, and distribute the
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`drug ELMIRON for the relief of bladder pain or discomfort associated with interstitial cystitis.
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`
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`FACTUAL BACKGROUND
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`55.
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`Pentosan polysulfate sodium (hereinafter referred to as “PPS”) is a semi-synthetically
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`produced low molecular weight heparin-like compound and is marketed in the United States by Defendants
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`under the name ELMIRON.
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`56.
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`Upon information and belief, Defendant TEVA R&D licenses ELMIRON to Defendant
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`JANSSEN PHARM, a wholly owned subsidiary of Defendant J&J, for manufacture, marketing, advertising,
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`distribution, and sale of ELMIRON in the United States, including in the State of New Jersey and the State
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`of North Carolina.
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`57.
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`Upon information and belief, the original New Drug Application (hereinafter referred to as
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`“NDA”) for ELMIRON was submitted by Baker Norton Pharmaceuticals, Inc. (hereinafter referred to as
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`“the sponsor”), which was owned by Ivax Corporation. Ivax Corporation licensed ELMIRON to Ortho-
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`McNeil Pharmaceutical, Inc. n/k/a Defendant JANSSEN PHARM. Defendant TEVA R&D then purchased
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`Ivax Corporation and continued to license ELMIRON to Defendant JANSSEN PHARM.
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`58.
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`59.
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`ELMIRON sales in the United States total more than $150 million each year.
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`ELMIRON was the first oral medication approved for use to relieve bladder pain or
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`discomfort associated with interstitial cystitis.
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`9
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`60.
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`Interstitial cystitis is a chronic bladder condition affecting millions of people, mainly
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`women, in the United States that causes increased bladder pressure, bladder pain, and even pelvic pain that
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`can often be severe. There is currently no cure for interstitial cystitis.
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`61.
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`On August 7, 1985, the United Sates Food and Drug Administration (hereinafter referred to
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`as “FDA”) designated ELMIRON an orphan drug product due to the rarity of interstitial cystitis.
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`62.
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`The sponsor submitted its first NDA for approval on June 11, 1991 which included data from
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`two clinical trials (referred to as study 001 and 002).
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`63.
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`On January 27, 1993, FDA issued its first non-approval letter due to numerous problems
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`with the clinical trial analyses and results, as well as interaction between the clinical trial investigators.
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`Specifically, FDA stated that the NDA lacked the requisite two (2) adequate and well-controlled studies for
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`determining the effects of ELMIRON. FDA requested that the sponsor conduct another well-controlled,
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`ideally blinded and randomized, clinical trial and to exclude certain investigators.
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`64.
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`In response, the sponsor declined to perform an additional clinical trial and instead re-
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`analyzed the data from the two pivotal studies already submitted.
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`65.
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`On October 28, 1994, FDA issued a second non-approval letter due to insufficient clinical
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`trial evidence to establish efficacy. Once again, the FDA emphasized that the studies could not be
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`considered independent due to issues with the investigators. In removing the data generated by those
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`investigators, neither study was powered to show statistical significance for any of the primary efficacy
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`endpoints. While FDA did find that study 002 provide some evidence of efficacy, it once again encouraged
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`the sponsor to perform another well-controlled, sufficiently powered clinical trial and to exclude any
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`investigators involved in study 002.
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`10
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`66.
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`The sponsor continued to decline to perform an additional clinical trial and instead proposed
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`an analysis of the database from its Compassionate Use program established in 1986, which it submitted to
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`FDA on August 31, 1995.
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`67.
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`Ultimately, for its third resubmission of the NDA, the sponsor relied on two clinical studies.
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`The first study (study 002) was a blinded, randomized, placebo-controlled trial that evaluated only 151
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`patients for three (3) months. Of the patients receiving ELMIRON, 38% reported greater than 50%
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`improvement in bladder pain compared to 18% of the placebo patients. FDA noted that the study indicated
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`a statistically significant treatment effect for only two (2) of six (6) identified efficacy endpoints – the
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`patient’s evaluation of bladder pain and the investigator’s evaluation of overall improvement – both of
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`which allow for bias that undermines the validity of the results. Further, FDA also noted that one
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`investigator in particular influenced the results, and when the data from that investigator were removed, the
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`results still favored ELMIRON over placebo but were no longer statistically significant.
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`68.
`
`The second clinical trial was an unblinded retrospective analysis of 2,499 patients, mostly
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`women, in the ELMIRON Compassionate Use program. After three (3) months, over half of the patients
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`dropped out or were deemed ineligible for the trial; importantly, 31% of those patients reported lack of
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`efficacy and 17% reported an adverse event. The number of patients reporting improvement in pain after
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`three (3) months of treatment was 61% but dropped to only 13% after six (6) months of treatment.
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`69.
`
`In reviewing the NDA for a third time, FDA accepted the Compassionate Use data in lieu of
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`a randomized controlled clinical trial, the typical gold standard. However, FDA noted that only a subset of
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`the patients was analyzed, and any observed efficacy from ELMIRON use could be enhanced by placebo
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`effect since the study was unblinded and uncontrolled.
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`11
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`70.
`
`In reviewing the clinical trial data overall, FDA noted that 75% of interstitial cystitis patients
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`could be classified as non-responders to ELMIRON therapy and recommended a three (3) month trial period
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`after drug initiation to determine if a patient will respond to ELMIRON.
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`71.
`
`On September 26, 1996, FDA ultimately approved the NDA for ELMIRON based on these
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`two studies despite the significant concerns. The FDA reviewers noted that, while the studies had fatal
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`flaws, the unique situation of interstitial cystitis, the apparent lack of significant clinical safety concerns
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`based on these short-term studies, and the appearance of efficacy in a subset of patients resulted in a small
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`risk/benefit ratio provided the sponsor agreed to an indication with a three-month initial treatment trial and
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`continued to monitor the safety and efficacy of ELMIRON.
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`72.
`
`Following approval in 1996, Defendants have received multiple Adverse Event Reports
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`(hereinafter referred to as “AERs”) detailing injuries including serious visual symptoms and/or damage
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`both in the United States and internationally.
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`73.
`
`Then, in Spring of 2018, a team at Emory Eye Center submitted a letter to the editor of the
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`Journal of Urology reporting findings of unusual retinal pigmentary changes or maculopathy (i.e., any
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`condition affecting the macula at the center of the retina) in six (6) female patients on long-term ELMIRON
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`treatment (median use of 15.5 years) that did not resemble any other type of retinal disease.1 That case
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`series was published online at the end of April 2018.2 None of the patients had family history of retinal
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`disease or any pathogenic process that would predispose them to such a disease. Of the six (6), five (5) had
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`received 400mg daily of ELMIRON (but two reduced their dose to 200mg pe day after 17 years of
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`treatment), and one (1) received 300mg daily. The youngest patient was 23 years old when diagnosed with
`
`
`1 Pearce WA, et al. Re: FDA BRUDAC 2018 Criteria for Interstitial Cystitis/Bladder Pain Syndrome Clinical Trials: Future
`Direction for Research. J Urol 2018;200(5):1122-1123.
`
` 2
`
` Pearce WA, et al. Pigmentary Maculopathy Associated with Chronic Exposure to Pentosan Polysulfate Sodium.
`Ophthalmology. 2018 May 22.
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`12
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`interstitial cystitis, began showing visual symptoms at 30, and by 37 had the most severe eye damage in the
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`study. The authors also highlighted the results of the Compassionate Use study that showed vision related
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`adverse events, including optic neuritis, amblyopia, and retinal hemorrhage.
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`74.
`
`In May 2019, the same Emory team presented an update to their study at the American
`
`Urological Association annual meeting in Chicago. The study identified 10 patients with pigmentary
`
`maculopathy at the Emory Eye Center. The patients ranged in age from 38 to 68 and once again had a
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`median treatment duration of 15.5 years (with the shortest duration of a little over two (2) years). The poster
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`presentation concluded:
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`We describe a potentially avoidable retinal degeneration phenomenon associated with
`chronic PPS exposure. Structural changes occur at the level of the retinal pigment
`epithelium, manifesting as characteristic pigmentary changes. While it remains unclear
`whether drug cessation will alter the course of retinal disease, we encourage affected patients
`to discontinue use, and patients with suggestive visual symptoms to undergo a
`comprehensive ophthalmic examination with OCT and FAF imaging.3
`
`The Emory researchers also presented at the Association for Research in Vision and
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`75.
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`Ophthalmology Annual Meeting at the end of Spring 2019 where they reported results from a retrospective
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`cross-sectional study that included all patients at Emory Eye Center who had been diagnosed with interstitial
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`cystitis within a four (4)-year period. The authors found 14 cases of this characteristic maculopathy in 80
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`patients exposed to ELMIRON and no cases in 139 unexposed patients. The only statistically significant
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`risk factor was ELMIRON exposure, with median use of 18.3 years in affected patients. The authors thereby
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`concluded a strong association between ELMIRON exposure and this specific type of vision-threatening
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`maculopathy.4
`
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`3 Foote, et al. 2019. Chronic Exposure to Pentosan Polysulfate Sodium is Associated with Retinal Pigmentary Changes and
`Vision Loss. AUA 2019 Abstract MP47-03.
`
` Hanif AM, et al. Strength of Association between Pentosan Polysulfate and a Novel Maculopathy. Ophthalmology. 2019
`Oct;126(10):1464-1466.
`
`
` 4
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`
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`13
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`Case 3:20-cv-14909-BRM-ZNQ Document 1 Filed 10/23/20 Page 14 of 58 PageID: 14
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`76.
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`The Emory research group then teamed with researchers at other institutions to conduct a
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`multi-institutional case series published in September 2019 that analyzed 35 patients with ELMIRON-
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`associated maculopathy. The median duration of use was 14.5 years at a median dose of 300mg per day.
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`The most common referral diagnosis was macular or pattern dystrophy and/or age-related macular
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`degeneration, and the most common symptoms included blurred vision and prolonged dark adaptation. This
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`study focused on diagnostic methods (i.e., multimodal imaging) and presentation of this specific form of
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`maculopathy, which proved distinctive from other retinal diseases and conditions.5
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`77.
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`In October 2019, a research team at Kaiser Permanente in Oakland, CA found that out of
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`140 patients currently using ELMIRON for an average of 15 years (and a minimum of five (5) years),
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`24% had eye damage and/or retinal toxicity that increased with the total amount of ELMIRON taken.
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`That team presented their research at the 2019 Annual meeting for the American Academy of
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`Ophthalmology in San Francisco.6 The researchers then performed multimodal image screening on 117
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`patients exposed to ELMIRON, of which 23% had definite indications of maculopathy and demonstrated
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`a dose-response relationship. Specifically, approximately one quarter of patients with an intake of greater
`
`than 500g developed retinal changes consistent with ELMIRON-associated maculopathy.7
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`78.
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`Another presentation at the October 2019 AAO meeting was “the first study to demonstrate
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`a dose-response correlation between exposure to [ELMIRON] and retinal toxicity.”8
`
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`5 Hanif A, et al. Phenotypic Spectrum of Pentosan Polysulfate Sodium-Associated Maculopathy: A Multicenter Study. JAMA
`Ophthalmol. 2019;137(11):1275-1282.
`
` 6
`
` “More Evidence Linking Common Bladder Medication to a Vision-threatening Eye Condition.” AAO Press Release. Oct. 12,
`2019.
`
` 7
`
` Vora RA, et al. Prevalence of Maculopathy Associated with Long-Term Pentosan Polysulfate Therapy. Ophthalmology. 2020
`June;127(6):835-836.
`
` 8
`
` Schaal, S. and Hadad, A. “Qualitative and Quantitative Analysis of Pentosan Polysulfate Sodium Retinal Toxicity
`Demonstrates a Dose-Response Curve.” AAO PA068 – 2019.
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`14
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`Case 3:20-cv-14909-BRM-ZNQ Document 1 Filed 10/23/20 Page 15 of 58 PageID: 15
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`79.
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`In November 2019, the Emory Eye Center team released results from a U.S. retrospective
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`cohort study using a medical claims database from 2002 to 2016 comparing ELMIRON users to matched
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`controls at five (5) and seven (7) years of use. At the seven (7) year follow-up, ELMIRON users had
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`significantly increased risk of developing atypical maculopathy and age-related macular degeneration.
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`Therefore, this study concluded that ELMIRON “exposure was associated with a new diagnosis of
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`macular disease at the 7-year follow-up in a large national cohort.”9
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`80.
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`Also, in November 2019, a researcher at Harvard published a case study of ELMIRON-
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`associated maculopathy that progressed over six (6) years after discontinuing the medication. The female
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`patient used 200mg per day for 18 years. She first presented with a year of visual symptoms at the age of
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`62 and stopped using ELMIRON shortly thereafter. She continued to be seen for increasing visual
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`damage over the course of the next six (6) years and was determined to have retinal atrophy and damage
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`that could not be associated with any genetic or other potential cause. Upon release of the Emory case
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`study in 2018, her treaters determined her case was consistent with ELMIRON-associated maculopathy.
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`The authors stated that this case, “adds a new layer of concern by demonstrating progressive maculopathy
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`continuing for up to 6 years after the cessation of [ELMIRON],” and called for screening that “balances
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`the demands of patients and physicians with the importance of prompt identification of early toxicity.”10
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`81.
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`In July 2020, researchers at Emory and other institutions published a retrospective case series
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`to evaluate the disease course of retinal pigmentary changes/maculopathy associated with ELMIRON use
`
`(referred to as “PPS-associated maculopathy”) after drug cessation. Of the 11 patients included in the study
`
`
`9 Jain N, et al. 2019. Association of macular disease with long-term use of pentosan polysulfate sodium: findings from a US
`cohort. Br. J. Ophthalmol. 2019 Nov 6.
`
`10 Huckfeldt R, et al. Progressive Maculopathy After Discontinuation of Pentosan Polysulfate Sodium. Ophthalmic Surgery,
`Lasers & Imaging Retina. 2019;50(10):656-659. Similar screening guidelines have been established for another drug,
`hydroxychloroquine, that has been similarly associated with vision damage. See Ferguson TJ, et al. Chronic use of pentosan
`polysulfate sodium associated with risk of vision-threatening disease. Intl. Urogynecology J. (2019) 30:337-338.
`
`
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`15
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`Case 3:20-cv-14909-BRM-ZNQ Document 1 Filed 10/23/20 Page 16 of 58 PageID: 16
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`with confirmed PPS-associated maculopathy, none of the patients exhibited demonstrable improvement
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`after discontinuing ELMIRON; in fact, nine (9) of the patients reported worsening visual symptoms.
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`Imaging confirmed expansion of the affected areas of the retina over time and even atrophy encroaching on