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Case 2:21-cv-00601-WB Document 1 Filed 02/09/21 Page 1 of 55
`
`ROBINS KAPLAN LLP
`Rayna E. Kessler, Esq.
`PA ID No. 309607
`399 Park Avenue, Suite 3600
`New York, New York 10022-4690
`Telephone: (212) 980-7431
`Facsimile: (212) 980-7499
`Email: RKessler@RobinsKaplan.com
`
`Kate Jaycox, Esq. (Pro hac Vice Motion to be Filed)
`Caroline Moos, Esq. (Pro hac Vice Motion to be Filed)
`2800 LaSalle Plaza
`800 LaSalle Avenue
`Minneapolis, MN 55402-2015
`Telephone: 612-349-8500
`Facsimile: 612-339-4181
`Email: KJaycox@RobinsKaplan.com
`
`CMoos@RobinsKaplan.com
`
`Attorneys for Plaintiffs Leah R. Smith and Akida Morgan
`
`IN THE UNITED STATES DISTRICT COURT FOR THE
`EASTERN DISTRICT OF PENNSYLVANIA
`
`LEAH R. SMITH and
`AKIDA MORGAN,
`
`Plaintiffs,
`
`v.
`LUITPOLD PHARMACEUTICALS, INC.,
`AMERICAN REGENT, INC.,
`DAIICHI SANKYO, INC.,
`DAIICHI SANKYO US HOLDINGS, INC.,
`VIFOR PHARMA LTD.,
`VIFOR PHARMA PARTICIPATIONS LTD.,
`VIFOR (INTERNATIONAL) AG, and
`RELYPSA INC.,
`
`
`Defendants.
`
`EASTERN DISTRICT OF PENNSYLVANIA
`PHILADELPHIA DIVISION
`
` CIVIL ACTION NO. 2:21-cv-00601-WB
`
`Civil Action
`Filed Electronically
`
`COMPLAINT
`AND JURY DEMAND
`
`
`
`1
`
`

`

`Case 2:21-cv-00601-WB Document 1 Filed 02/09/21 Page 2 of 55
`
`Plaintiffs Leah R. Smith and Akida Morgan, by and through their undersigned counsel,
`
`bring this civil action against the above-named Defendants for personal injuries and damages,
`
`and allege as follows:
`
`PARTIES
`
`1.
`
`Plaintiffs Leah R. Smith and Akida Morgan reside in Robertsdale, Alabama.
`
`Plaintiffs Smith and Morgan are married. Plaintiff Smith suffered serious physical injuries and
`
`economic damages due to her use of the injectable iron product, Injectafer (ferric
`
`carboxymaltose).
`
`The American Regent Defendants
`
`2.
`
`Defendant Luitpold Pharmaceuticals, Inc. (“Luitpold”) was a New York
`
`corporation. At all relevant times, Luitpold maintained its principal offices in Norristown,
`
`Pennsylvania and Shirley, New York and was registered to do business throughout Pennsylvania,
`
`including within the county of Philadelphia. Luitpold was the parent to its subsidiary, American
`
`Regent, Inc.
`
`3.
`
`At all relevant times, and within Pennsylvania, Luitpold engaged in the business
`
`of researching, developing, designing, testing, licensing, manufacturing, distributing, supplying,
`
`selling, labeling, promoting, marketing, and/or introducing into commerce the Injectafer product.
`
`Luitpold was the Sponsor of the New Drug Application (“NDA”) submitted to the FDA on
`
`Injectafer in 2013.
`
`4.
`
`Defendant American Regent, Inc. (“American Regent”) is a New York
`
`corporation. At all relevant times, American Regent had a principal place of business at in Shirley,
`
`New York, sharing an office with Luitpold. Upon information and belief, American Regent also
`
`operates out of its Norristown, Pennsylvania office and is registered to do business in
`
`2
`
`

`

`Case 2:21-cv-00601-WB Document 1 Filed 02/09/21 Page 3 of 55
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`Pennsylvania. American Regent was a subsidiary of Luitpold until approximately December 31,
`
`2008.
`
`5.
`
`Upon information and belief, on or about December 31, 2008, Luitpold merged
`
`American Regent into itself, and the surviving entity – Luitpold – was renamed American
`
`Regent.1 The new entity of American Regent is a wholly owned subsidiary of Daiichi Sankyo,
`
`Inc.
`
`6.
`
`At all relevant times, and within Pennsylvania, American Regent has engaged in
`
`the business of researching, developing, designing,
`
`testing,
`
`licensing, manufacturing,
`
`distributing, supplying, selling, labeling, promoting, marketing, and/or introducing into
`
`commerce the Injectafer product.
`
`7.
`
`Luitpold was the primary holder of a license to manufacture and market Injectafer
`
`from Vifor (International) Inc. until the merger. American Regent is the manufacturer currently
`
`listed on the Injectafer label, still under license from Vifor (International) Inc.
`
`8.
`
`Upon information and belief, both American Regent and Luitpold were and are
`
`part of the Daiichi Sankyo Group.
`
`The Daiichi Sankyo Defendants
`
`9.
`
`Defendant Daiichi Sankyo, Inc. (“DSI”) is a Delaware corporation with its
`
`principal place of business in Basking Ridge, New Jersey. DSI is the United States subsidiary of
`
`Daiichi Sankyo Co., Ltd. (“DSC”), located in Tokyo, Japan, and is a member of the Daiichi
`
`Sankyo Group. DSI is wholly owned by Defendant Daiichi Sankyo U.S. Holdings, Inc.
`
`10.
`
`Defendant Daiichi Sankyo U.S. Holdings, Inc. (“DS Holdings”) is a Delaware
`
`                                                            
`1 Since the merger between Luitpold and American Regent resulted in an entity called American
`Regent, any allegation throughout the Complaint specific to Luitpold also applies to its successor,
`American Regent.
`
`3
`
`

`

`Case 2:21-cv-00601-WB Document 1 Filed 02/09/21 Page 4 of 55
`
`corporation with its principal place of business in Basking Ridge, New Jersey. DS Holdings
`
`wholly owns DSI. Upon information and belief, DS Holdings is also a subsidiary of DSC and is
`
`a member of the Daiichi Sankyo Group.
`
`11.
`
`Upon information and belief, DSI is or was also known as Sankyo USA
`
`Development, Sankyo Pharma Development, Sankyo Pharma, Inc., Daiichi Sankyo Group, and
`
`Daiichi Pharma Holdings, Inc. Upon information and belief, DSI operates as the U.S.
`
`headquarters of DSC.
`
`12.
`
`At all relevant times, DSI is and was engaged in the business of researching,
`
`developing, designing, licensing, manufacturing, distributing, and selling the Injectafer product.
`
`Starting in or around January 2017, DSI assumed the role of promoting and marketing Injectafer
`
`in the United States.
`
`13.
`
`Upon information and belief, at all relevant times, DSI exercised control over the
`
`DSI subsidiaries, Luitpold and American Regent, with control over all relevant decisions,
`
`policies, and conduct regarding the research, development, design, licensing, manufacture,
`
`distribution, marketing, promotion, and selling of Injectafer.
`
`14.
`
`Upon information and belief, DS Holdings is and was at all times engaged in the
`
`business of researching, developing, designing, licensing, manufacturing, distributing, and
`
`selling the Injectafer product.
`
`15.
`
`Upon information and belief, DS Holdings exercised ultimate control, and was
`
`responsible for the actions and omissions of its wholly owned subsidiary, DSI.
`
`16.
`
`Upon information and belief, there existed at all relevant times a unity of interest
`
`in ownership between DS Holdings and DSI such that independence from, or separation between,
`
`these two Defendants does not and has never existed. Each of them is an alter ego of the other.
`
`4
`
`

`

`Case 2:21-cv-00601-WB Document 1 Filed 02/09/21 Page 5 of 55
`
`17.
`
`Because of the unity of operations and ownership, DSI and DS Holdings are
`
`hereinafter referred to as the “Daiichi Sankyo Defendants.”
`
`The Vifor Defendants
`
`18.
`
`Defendant Vifor Pharma Ltd. (“Vifor Pharma”) is a for-profit corporation
`
`headquartered, organized, and existing under the laws of Switzerland, with an office location at
`
`Rechenstrasse 37 CH-9014 St. Gallen.
`
`19.
`
`Defendant Vifor Pharma Participations Ltd. (“Vifor Participations”) is a for-profit
`
`corporation headquartered, organized, and existing under the laws of Switzerland, with an office
`
`location at Rechenstrasse 37 CH-9014 St. Gallen. Vifor Participations is a wholly owned
`
`subsidiary of Vifor Pharma.
`
`20.
`
`Defendant Vifor (International) AG a/k/a Vifor (International) Inc. (“Vifor
`
`International”) is a for-profit corporation headquartered in Switzerland with an office location at
`
`Rechenstrasse 37 CH-9014 St. Gallen. Vifor International is a wholly owned subsidiary of Vifor
`
`Participations, Ltd.
`
`21.
`
`Defendant Relypsa Inc. (“Relypsa”) is Delaware corporation with its principal
`
`office in Redwood City, California. Relypsa Inc. is a wholly owned subsidiary of Vifor Pharma,
`
`and a United States Corporate Affiliate of Vifor International.
`
`22.
`
`Because of the unity of operations and ownership, Vifor Pharma, Vifor
`
`Participations, Vifor International, and Relypsa are hereinafter referred to as the “Vifor
`
`Defendants” or “Vifor.”
`
`23.
`
`The Vifor Defendants are in the business of researching, developing, designing,
`
`licensing, manufacturing, distributing, supplying, selling, marketing, and/or introducing into
`
`commerce ferric carboxymaltose, or its European brand bioequivalent, Ferinject.
`
`5
`
`

`

`Case 2:21-cv-00601-WB Document 1 Filed 02/09/21 Page 6 of 55
`
`24.
`
`Upon information and belief, the Vifor Defendants for responsible for the original
`
`design and development of the bioequivalent ferric carboxymaltose product, branded as Ferinject
`
`in Europe.
`
`25.
`
`Upon information and belief, the Vifor Defendants, by and through Vifor
`
`International, licensed ferric carboxymaltose to Luitpold, permitting Luitpold to design,
`
`manufacture, market, supply, promote, label, distribute, and sell ferric carboxymaltose in the
`
`United States, branded as Injectafer. Vifor International was the international “partner” of
`
`Luitpold in the sale of Injectafer. The licensing agreement between Vifor International and
`
`Luitpold awards Vifor International a “share of partner sales” in regards to Injectafer sales in the
`
`United States.
`
`26.
`
`Pursuant to this licensing deal and other agreements, the Vifor Defendants
`
`assumed a role in the conducting and management of the clinical trials, marketing, promotion,
`
`marketing sales organization, and pharmacovigilance for Injectafer.
`
`27.
`
`Upon information and belief, the Vifor Defendants provide support to American
`
`Regent and DSI, on
`
`the design, manufacture, distribution, marketing, promotions,
`
`pharmacovigilance, and/or sale of Injectafer.
`
`28.
`
`Pursuant to 21 C.F.R. § 207 (2019), foreign manufacturers of a pharmaceutical drug
`
`that is imposed or offered into the United States must have a Registered Agent. Vifor’s Registered
`
`Agent in the United States is American Regent.
`
`29.
`
`Since initially introducing ferric carboxymaltose into the world market, Vifor
`
`Pharma, and its subsidiaries, have been in the business of collecting, supervising, analyzing, and
`
`reporting adverse events, peer-reviewed literature, clinical and nonclinical studies, and other
`
`epidemiology on ferric carboxymaltose.
`
`6
`
`

`

`Case 2:21-cv-00601-WB Document 1 Filed 02/09/21 Page 7 of 55
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`30.
`
`Each of the above Defendants played a role in the design, manufacture, distribution,
`
`marketing, promotion, pharmacovigilance, and/or sale of Injectafer. Plaintiffs’ injuries were
`
`caused by the conduct of one or various combinations of Defendants, and through no fault of
`
`Plaintiffs.
`
`JURISDICTION AND VENUE
`
`31.
`
`This action is properly before this Court pursuant to 28 U.S.C. § 1332(a) because
`
`complete diversity of citizenship exists between Plaintiffs and Defendants, the amount in
`
`controversy exceeds $75,000, exclusive of interest and costs. Defendants have engaged in
`
`continuous and systematic business activities in the Commonwealth of Pennsylvania.
`
`32.
`
`This Court has personal jurisdiction over Defendants pursuant to § 42 Pa. C.S.
`
`5301 et seq., because, at all relevant times, Defendants have carried on continuous and systematic
`
`business activities within the Commonwealth of Pennsylvania.
`
`33.
`
`This Court has general personal jurisdiction over the Luitpold, American Regent,
`
`and DSI Defendants because each is registered to do business in Pennsylvania and therefore has
`
`consented to general personal jurisdiction in Pennsylvania, 42 Pa. C.S. § 5301 and 42 Pa. C.S. §
`
`5322.
`
`34.
`
`This Court has general personal jurisdiction over the Vifor Defendants, which do
`
`business in Pennsylvania. The Vifor Defendants, by and through Vifor International, engaged in
`
`a licensing deal for its ferric carboxymaltose product that would see the continuous and systemic
`
`sale of Injectafer in Pennsylvania. The Vifor Defendants, by and through the Vifor affiliates
`
`including, but not limited to, Relypsa, manage the sale of Injectafer in the United States, including
`
`in the Commonwealth of Pennsylvania, and provide support to American Regent and DSI on the
`
`design, manufacture, distribution, marketing, promotion, pharmacovigilance, and/or sale of
`
`7
`
`

`

`Case 2:21-cv-00601-WB Document 1 Filed 02/09/21 Page 8 of 55
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`Injectafer. Vifor’s Registered Agent is American Regent. Vifor Pharma and Vifor Participations,
`
`as the parents and alter ego to Vifor International and Relypsa, thus have inextricable ties to
`
`Pennsylvania.
`
`35.
`
`This court has general personal jurisdiction over Luitpold and American Regent
`
`because they operate an office and principal place of business at 800 Adams Street, Norristown,
`
`Pennsylvania 19403, which is located in the Eastern District of Pennsylvania.
`
`36.
`
`This Court has personal jurisdiction over each of the Defendants pursuant to 42
`
`Pa. C.S. 5322.
`
`37.
`
`This Court has specific personal jurisdiction over the Defendants due to the
`
`Injectafer-specific business activities that give rise to this claim, including but not limited to the
`
`development, testing, pharmacovigilance, safety monitoring, promotion, and sale of Injectafer
`
`that take place in parts of the Commonwealth of Pennsylvania which are located in the Eastern
`
`District of Pennsylvania.
`
`38.
`
`Upon information and belief, Luitpold headquartered its Clinical Division at its
`
`office in Norristown, Pennsylvania. Norristown was also home to Luitpold’s clinical Research
`
`and Development Department, to the extent that group existed separately from the Clinical
`
`Division. Upon information and belief, following the merger, American Regent is now the sole
`
`operating corporate entity at the Norristown, Pennsylvania location.
`
`39.
`
`Upon information and belief, Luitpold’s Regulatory Affairs Department also
`
`operated out of the Norristown, Pennsylvania office. Specifically, Marsha E. Simon, Director of
`
`Regulatory Affairs, was employed in the Norristown office and used the Norristown address
`
`when making regulatory submission on behalf of Luitpold and Injectafer to the Food and Drug
`
`Administration (“FDA”).
`
`8
`
`

`

`Case 2:21-cv-00601-WB Document 1 Filed 02/09/21 Page 9 of 55
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`40.
`
`Luitpold’s Norristown, Pennsylvania office served as either the monitoring site,
`
`organizational headquarters, or specific location for pivotal Injectafer clinical studies run by
`
`Defendants.
`
`41.
`
`Upon information and belief, the Norristown office is also the location from which
`
`Luitpold conducted its pharmacovigilance and safety reporting for Injectafer. Many of the
`
`Injectafer pharmacovigilance and safety positions were employed at the Norristown,
`
`Pennsylvania office, including Luitpold’s Senior Medical Director, Clinical Quality Assurance,
`
`Senior Clinical Project Manager, and Clinical Research Associate.
`
`42.
`
`Consequently, Luitpold’s pharmacovigilance, medical affairs, clinical design, and
`
`regulatory functions related to Injectafer were all conducted in the Norristown, Pennsylvania
`
`location – either in whole or in substantial part.
`
`43.
`
`Pursuant to the licensing and safety agreements between Vifor International and
`
`Luitpold, the Vifor Defendants directly participated in the registration and clinical trials,
`
`marketing, promotions and sales, adverse events arising
`
`from clinical
`
`trial, and
`
`pharmacovigilance obligations for Injectafer, which – either in whole or in substantial part – were
`
`conducted or managed in Luitpold’s Norristown, Pennsylvania office.
`
`44.
`
`In addition, the Vifor Defendants, by and through Relypsa and other Vifor entities,
`
`and in conjunction with American Regent, are engaged in the design, manufacture, distribution,
`
`marketing, promotion, pharmacovigilance, and/or sale of Injectafer, which – either in whole or
`
`in substantial part – were conducted or managed in Luitpold’s Norristown, Pennsylvania office.
`
`45.
`
`All other Defendants, as either subsidiary, parent, or licensing partner to Luitpold
`
`and American Regent, similarly engaged in the aforementioned development, testing,
`
`pharmacovigilance, and safety reporting functions for Injectafer in Pennsylvania. Injectafer was
`
`9
`
`

`

`Case 2:21-cv-00601-WB Document 1 Filed 02/09/21 Page 10 of 55
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`also specifically promoted, marketed, and sold throughout Pennsylvania.
`
`46.
`
`Defendants regularly conduct substantial business within the Eastern District of
`
`Pennsylvania.
`
`47.
`
`Injectafer is marketed, promoted, distributed, and sold to hospitals, medical
`
`facilities, infusion centers, home health care agencies, and consumers in the Philadelphia region
`
`within the Eastern District of Pennsylvania.
`
`48.
`
`Venue is proper pursuant to 28 U.S.C. § 1391(b) in the Eastern District of
`
`Pennsylvania because Defendants American Regent and Luitpold operate an office out of
`
`Norristown, Pennsylvania.
`
`49.
`
`Venue
`
`is proper
`
`in
`
`the Eastern District of Pennsylvania pursuant
`
`to
`
`28 U.S.C. § 1391(b)(2) because substantial, specific conduct by Luitpold, American Regent, and
`
`the Vifor Defendants that gave rise to this claim originated and occurred in Defendants’
`
`Philadelphia region office.
`
`50.
`
`At all relevant times, Defendants have engaged in continuous and systematic
`
`business activities in the Commonwealth of Pennsylvania. Defendants have significant contacts
`
`with this District by virtue of their many operations and doing business within this judicial
`
`district.
`
`FACTUAL BACKGROUND
`
`Iron Deficiency and Injectafer Overview
`
`51.
`
`Injectafer (compound: ferric carboxymaltose) is an iron replacement injection
`
`medication manufactured by Defendants indicated “for the treatment of iron deficiency anemia
`
`(IDA) in adult patients who have intolerance to oral iron or have had unsatisfactory response to
`
`oral iron, or in adult patients with non-dialysis dependent chronic kidney disease.”
`
`10
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`

`

`Case 2:21-cv-00601-WB Document 1 Filed 02/09/21 Page 11 of 55
`
`52.
`
`Iron is an essential mineral which the body uses produce hemoglobin, a protein
`
`within red blood cells that transports oxygen throughout the body to tissues. Most of the body’s
`
`iron is in hemoglobin; the remainder is stored in the liver, spleen, bone marrow or is located in
`
`myoglobin in muscles. Iron helps produce myoglobin, another protein that provides oxygen and
`
`is found mainly in muscles. Among other jobs, iron plays an essential role in cellular functioning,
`
`immune function, neurological development, and synthesis of some hormones.2
`
`53.
`
`People in the United States generally obtain adequate iron intake from food, but
`
`iron deficiency can be commonly caused by a lack of iron in one’s diet, blood loss, an inability
`
`to absorb iron, or pregnancy. Certain populations are more at risk of having low iron levels,
`
`including women, infants and children, vegetarians, and those with conditions causing blood
`
`loss.3
`
`54.
`
`Iron deficiency anemia (“IDA”) occurs with insufficient levels of iron in an
`
`individual’s body. While mild or moderate IDA may not cause symptoms, more severe IDA may
`
`result in pale skin, fatigue, shortness of breath, chest pain, and headache, among other symptoms.4
`
`55.
`
`IDA rates vary by gender and race. IDA occurs 2% of men, 9 to 12% of non-
`
`Hispanic white women, and nearly 20% of black and Mexican-American women.5
`
`Approximately ten million people in the United States are iron deficient, and five million people
`
`                                                            
`Iron Fact Sheet
`
`of Health,
`2
`See National
`Institute
`https://ods.od.nih.gov/factsheets/Iron-HealthProfessional/
`
`for Professionals,
`
` 3
`
` See National Heart, Lung, and Blood Institute, Iron-Deficiency Anemia, available at
`https://www.nhlbi.nih.gov/health-topics/iron-deficiency-anemia
`
` 4
`
` See https://www.hematology.org/education/patients/anemia/iron-deficiency
`
` 5
`
` See Killp, S. et al, Iron Deficiency Anemia, Am Fam Physician. 2007 Marc 1: 75(5):671-678),
`available at https://www.aafp.org/afp/2007/0301/p671.html
`
`11
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`

`Case 2:21-cv-00601-WB Document 1 Filed 02/09/21 Page 12 of 55
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`have IDA.6
`
`56.
`
`For years, IDA was treated primarily with oral iron supplements. Early forms of
`
`intravenous iron caused severe complications, and doctors recommended these only in extreme
`
`conditions. Starting in about the 1990s, the pharmaceutical industry began introducing intravenous
`
`iron supplements, for those unwilling or unable to take oral iron supplements.
`
`57.
`
`Defendants Luitpold and American Regent brought Injectafer to the United States
`
`market in 2013, at the direction and under the control of their parent, the Daiichi Sankyo
`
`Defendants.
`
`58.
`
`Prior to 2013, the compound ferric carboxymaltose (“FCM”) was available on the
`
`European and other markets under the brand name of Ferinject. Ferinject was designed,
`
`manufactured, promoted, and sold by the Vifor Defendants, by and through Vifor International.
`
`Defendant Vifor International licensed and continues to license FCM to all other Defendants who
`
`in turn have designed, manufactured, and sold the product in the United States. The Vifor
`
`Defendants provide support to American Regent and DSI on the design, manufacture, distribution,
`
`marketing, promotion, pharmacovigilance, and/or sale of Injectafer in the United States.
`
`59.
`
`Intended for rapid and high-dose iron replenishment, in the United States,
`
`Injectafer is to be administered intravenously in two doses separated by at least 7 days. For those
`
`weighing over 100 pounds, each dose should be for 750 mg, for a total cumulative dose of 1500
`
`mg of iron per course of Injectafer.
`
`60.
`
`Injectafer is one of several products available for intravenous iron, but the only
`
`product available in the United States formulated with the unique FCM compound.
`
`                                                            
`6 Miller, J. Iron Deficiency Anemia: A Common and Curable Disease, Cold Spring Harb Perspect
`Med. 2013 Jul; 3 (7), available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3685880/
`
`12
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`61.
`
`Unlike the other intravenous iron products available, FCM causes a condition called
`
`“Severe Hypophosphatemia” (“Severe HPP”) and potentially “persistent hypophosphatemia”
`
`(“Persistent HPP”).
`
`62.
`
`Hypophosphatemia (“HPP”) is an electrolyte disturbance in which there is an
`
`abnormally low level of phosphate in the body. HPP is rare in the United States and it almost
`
`never results from low dietary intakes. Instead – apart from being caused by FCM – HPP is most
`
`often caused by medical conditions, such as diabetic ketoacidosis, kidney tubule defects,
`
`hyperparathyroidism, rare genetic phosphate regulation disorders, and severe malnutrition
`
`causing refeeding syndrome.7
`
`63.
`
`Phosphorous, or serum or plasma phosphate, is an essential mineral in the body
`
`and vital to several of the body’s physiological processes. Most phosphorus is stored in the bones,
`
`with the rest stored in tissues throughout the body.8 Phosphorus is a component of bones, teeth,
`
`DNA, and RNA. Phosphorous helps with bone growth, energy storage, and nerve and muscle
`
`production. Phosphate has a “widespread role in nearly every molecular, cellular function,” so
`
`abnormal phosphate levels can have high impact on an individual.9
`
`64.
`
`There are several levels of hypophosphatemia, including mild, moderate, and
`
`severe. Agreed upon serum phosphate measurements for each level vary, but typically the
`
`                                                            
`7 See U.S. Department of Health & Human Services, National Institutes of Health, Phosphorus:
`Fact Sheet for Health Professionals, available at https://ods.od.nih.gov/factsheets/Phosphorus-
`HealthProfessional/
`
` 8
`
` See U.S. Department of Health & Human Services, National Institutes of Health, Phosphorus:
`Fact Sheet for Health Professionals, available at https://ods.od.nih.gov/factsheets/Phosphorus-
`HealthProfessional/
`
` 9
`
` See Sharma, S. et al., Hypophosphatemia. StatPearls, updated June 4, 2020, available at
`https://www.ncbi.nlm.nih.gov/books/NBK493172/
`
`13
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`Case 2:21-cv-00601-WB Document 1 Filed 02/09/21 Page 14 of 55
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`measurements break down as: 2.5 – 4.5 mg/dl serum phosphate (normal range); 2.0 – 2.5 mg/dl
`
`serum phosphate (mild hypophosphatemia); 1.0 – 2.0 mg/dl serum phosphate (moderate
`
`hypophosphatemia); and less than 1.0 mg/dl serum phosphate (severe hypophosphatemia). Severe
`
`HPP has also been identified in literature as levels less than 1.5 mg/dl or 1.3 mg/dl.
`
`65.
`
`Additionally, “persistent hypophosphatemia” is a condition in which an individual
`
`can suffer from HPP or Severe HPP for a sustained period.
`
`66.
`
`There are clinically significant differences between mild HPP (2.0 –2.5 mg/dl) and
`
`Severe HPP (less than 1.5, 1.3, or 1.0 mg/dl). While mild HPP can occur without symptomatology
`
`or injury, Severe HPP is a dangerous condition that can cause muscle weakening, severe fatigue,
`
`severe nausea, and can lead to serious medical complications including osteomalacia,
`
`arrhythmias, cardiac arrest, respiratory failure, and/or rhabdomyolysis.
`
`67.
`
`The dangers of Severe HPP are not just brought on by the extremely low levels of
`
`one’s serum phosphate, but also the duration (or prolonged period) of the Severe HPP.
`
`Laws and Regulations Governing the Approval of Labeling Prescription Drugs
`
`68.
`
`The Federal Food, Drug and Cosmetic Act (“FDCA” or the “Act”) requires
`
`manufacturers that develop a new drug product to file a New Drug Application (“NDA”) in order
`
`to obtain approval from the Food and Drug Administration (“FDA”) before selling the drug in
`
`interstate commerce. 21 U.S.C. § 355.
`
`69.
`
`The NDA must include, among other things, all data regarding the safety and
`
`effectiveness of the drug, information on any patents that purportedly apply to the drug or a
`
`method of using the drug and the labeling proposed to be used for the drug. 21 U.S.C. § 355(b).
`
`70. Manufacturers with an approved NDA must review all adverse drug experience
`
`information obtained by or otherwise received by them from any source, foreign or domestic,
`
`14
`
`

`

`Case 2:21-cv-00601-WB Document 1 Filed 02/09/21 Page 15 of 55
`
`including but not limited to information derived from commercial marketing experience, post
`
`marketing clinical investigations, post marketing epidemiological/surveillance studies, reports in
`
`the scientific literature and unpublished scientific papers. 21 C.F.R. § 314.80(b).
`
`71.
`
`After FDA approval, manufacturers may only promote drugs in a manner
`
`consistent with the contents of the drug’s FDA-approved label. 21 C.F.R. § 202.1.
`
`72.
`
`The primary responsibility for timely communicating complete, accurate and
`
`current safety and efficacy information related to prescription drugs rests with the NDA holders
`
`and their assigns or agents - and not the FDA. NDA holders have superior, and in many cases
`
`exclusive, access to the relevant safety and efficacy information, including clinical trial
`
`information and post-market complaints and data
`
`73.
`
`Although the FDA eventually approves the label submitted to the FDA by the
`
`manufacturer, it is the duty of the drug manufacturer to warn of dangerous adverse reactions that
`
`may be associated with its drug and to ensure the label is up to date and/or accurate. 21 CFR §
`
`201, et. seq.
`
`74.
`
`Under the FDCA, a drug’s label must contain specific “highlight” prescribing
`
`information regarding indicated usage, dosage form, route of administration, and approval
`
`information. 21 C.F.R. § 201.57. In order to inform prescribing physicians of the potential risks
`
`of a drug, and therefore to protect patients, the highlights portion of a label must also include
`
`multiple sections that the United States Supreme Court has described as ranked to reflect their
`
`relative “severity of risk.” Merck Sharp & Dohme Corp. v. Albrecht, 139 S. Ct. 1668, 1673
`
`(2019). This ensures that important safety information is overt.
`
`75.
`
`The most severe risks—those that could lead to death or serious injury—are to be
`
`contained in a “Boxed Warning.” 21 C.F.R. § 201.57(c)(1).
`
`15
`
`

`

`Case 2:21-cv-00601-WB Document 1 Filed 02/09/21 Page 16 of 55
`
`76.
`
`The next risk level is contained in the “Contraindications” section of the label,
`
`reserved for circumstances in which a drug should not be used due to the potential risks
`
`outweighing any therapeutic benefit. 21 C.F.R. § 201.57(9).
`
`77.
`
`The third level of severity is contained in the “Warnings and Precautions” section
`
`of the label. 21 C.F.R. § 201.57(a)(9). This section “must describe clinically significant adverse
`
`reactions (including any that are potentially fatal, are serious even if infrequent or can be
`
`prevented or mitigated through appropriate use of the drug), other potential safety hazards
`
`(including those that are expected for the pharmacological class or those resulting from drug/drug
`
`interactions), limitations in use imposed by them (e.g., avoiding certain concomitant therapy) and
`
`steps that should be taken if they occur (e.g., dosage modification). The frequency of all clinically
`
`significant adverse reactions and the approximate mortality and morbidity rates for patients
`
`experiencing the reaction, if known and necessary for the safe and effective use of the drug, must
`
`be expressed as provided under paragraph (c)(7) of this section.” 21 C.F.R. § 201.57(c)(6)(i).
`
`78.
`
`The Warnings and Precautions “section must contain information regarding any
`
`special care to be exercised by the practitioner for safe and effective use of the drug (e.g.,
`
`precautions not required under any other specific section or subsection).” 21 C.F.R.
`
`§ 201.57(c)(6)(ii).
`
`79.
`
`The Warnings and Precautions section of the label “must identify any laboratory
`
`tests helpful in following the patient’s response or in identifying possible adverse reactions. If
`
`appropriate, information must be provided on such factors as the range of normal and abnormal
`
`values expected in the particular situation and the recommended frequency with which tests
`
`should be performed before, during and after therapy.” Id. § 201.57(c)(6)(iii). According to an
`
`FDA Guidance for Industry on the Warnings and Precautions section of the labeling,
`
`16
`
`

`

`Case 2:21-cv-00601-WB Document 1 Filed 02/09/21 Page 17 of 55
`
`“[i]nformation about the frequency of testing and expected ranges of normal and abnormal values
`
`should also be provided if available.”10
`
`80.
`
`Risks with the lowest level of severity are included in the “Adverse Reactions”
`
`section of the label. 21 C.F.R. § 201.57(a)(11). Adverse reactions are “the most frequently
`
`occurring adverse reactions” that have not been included in other sections of the label. 21 C.F.R.
`
`§ 201.57(a)(11)(i).
`
`81.
`
`To fulfill their essential responsibilities, NDA holders/drug sponsors must
`
`accurately report clinical trial information and must closely evaluate the post-market clinical
`
`experience of their drugs, timely providing updated safety and efficacy information to the
`
`healthcare community and to consumers.
`
`82.
`
`A drug is “misbranded” in violation of the FDCA when its labeling is false and
`
`misleading, omits material facts regarding possible consequences from use, or does not provide
`
`adequate directions for use and adequate warnings. See 21 U.S.C. §§ 321(n); 331(a) and (b);
`
`352(f). A drug’s labeling satisfies federal requirements if it gives medical practitioners sufficient
`
`information—including indications for use and “any relevant hazards, contraindications, side
`
`effects, and precautions”—to allow those professionals “to use the drug safely and for the
`
`purposes
`
`for
`
`which
`
`it
`
`is
`
`intended.”
`
`21
`
`C.F.R.
`

`
`201.100(c)(1).
`
`83.
`
`As part of their responsibility to monitor post-market clinical experiences with the
`
`drug and provide updated safety and efficacy information to the healthcare community and to
`
`                                                            
`10 Guidance Document: Warnings and, Contraindications, and Boxed Warning Sections of
`Labeling for Human Prescription Drug and Biological Products – Content and Format, October
`2011,
`WWW.FDA.GOV,
`https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/
`UCM075096.pdf (last visited, January 5, 2021).
`
`17
`
`

`

`Case 2:21-cv-00601-WB Document 1

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