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`IN RE INCRETIN-BASED
`THERAPIES PRODUCTS LIABILITY
`LITIGATION
`
`
`As to All Related and Member Cases
`
`
`
`UNITED STATES DISTRICT COURT
`SOUTHERN DISTRICT OF CALIFORNIA
`
` Case No.: 13-md-2452-AJB-MDD
`
`OMNIBUS ORDER:
`
`(1) GRANTING DEFENDANTS’
`JOINT MOTION FOR SUMMARY
`JUDGMENT BASED ON
`PREEMPTION (Doc. No. 3594);
`
`(2) GRANTING DEFENDANTS’
`JOINT MOTION TO EXCLUDE
`DRS. MADIGAN, WELLS, BROWN,
`AND GALE (Doc. No. 3586);
`
`(3) GRANTING DEFENDANTS’
`JOINT MOTION TO EXCLUDE
`DRS. LANDOLPH, WOOLF, AND
`TAYLOR (Doc. No. 3521);
`
`(4) DENYING AS MOOT
`PLAINTIFFS’ MOTION TO
`EXCLUDE DRS. THAYER, WANG,
`AND SCHARFSTEIN (Doc. No. 3613);
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`(5) GRANTING DEFENDANT
`MERCK’S MOTION FOR
`SUMMARY JUDGMENT BASED ON
`CAUSATION (Doc. No. 3524);
`
`(6) GRANTING DEFENDANTS
`AMYLIN AND LILLY’S MOTION
`FOR SUMMARY JUDGMENT
`BASED ON CAUSATION
`(Doc. No. 3525); and
`
`(7) GRANTING DEFENDANT
`NOVO’S MOTION FOR SUMMARY
`JUDGMENT BASED ON
`CAUSATION (Doc. No. 3585).
`
`
`I.
`
`INTRODUCTION
`Pancreatic cancer is an unrelenting disease, occurring at a rate of more than 50,000
`cases a year. It is a leading cause of cancer-related death in the United States and has
`caused, and continues to cause, much suffering to tens of thousands of Americans each
`year. This multidistrict litigation involves claims that Defendants failed to warn that four
`prescription brand-name drugs used to treat type 2 diabetes cause, or increase the risk of,
`pancreatic cancer. Plaintiffs are individuals diagnosed with type 2 diabetes who were
`prescribed and consumed one or more of the following prescription drugs: Byetta, Januvia,
`Janumet, and Victoza. Defendants are the pharmaceutical companies that manufacture and
`market the drugs: Amylin Pharmaceuticals, LLC (“Amylin”), Eli Lilly and Company
`(“Lilly”), Merck Sharp & Dohme Corp. (“Merck”), and Novo Nordisk Inc. (“Novo”)
`(collectively, “Defendants”).
`The drugs are sometimes referred to by their active ingredients.1 Exenatide is the
`active ingredient in Amylin and Lilly’s Byetta. Sitagliptin is the active ingredient in
`
`
`1 For purposes of this Order, the Court will use the drug’s brand name and its active ingredient
`interchangeably.
`
`2
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`Merck’s Januvia and Janumet. Liraglutide is the active ingredient in Novo’s Victoza. The
`therapies involve incretin hormones, which operate in the body to lower blood sugar by
`stimulating or sustaining production of insulin. Exenatide and liraglutide are glucagon-like
`peptide-1 (“GLP-1”) receptor agonists (“GLP-1 RAs”). Sitagliptin is a dipeptidyl
`peptidase-4 (“DPP-4”) inhibitor (“DPP-4i”). Although the therapies are different classes
`of drugs, the FDA has generally reviewed and recognized them under the broader terms of
`incretin mimetics or incretin-based therapies. Up until now, the parties did too, focusing
`their arguments on incretin-based drugs collectively. Now, their arguments also discuss the
`drugs separately and with respect to their classification as either a GLP-1 RA or DPP-4i.
`Through the enactment of the Federal Food, Drug, and Cosmetics Act, 21 U.S.C.
`§ 301 et seq. (“FDCA”), Congress delegated authority to the Food and Drug
`Administration (“FDA”) to regulate pharmaceutical manufacturers and their products.
`With subsequent amendments, Congress enlarged this authority, charging the FDA with
`the power to protect the public health, and to assure the safety, effectiveness, and reliability
`of drugs. In discharging its regulatory duties, the FDA oversees the introduction of new
`drugs into the market, regulates the content of drug labeling, and ensures manufacturers
`comply with post-marketing requirements. Despite the FDA’s broad regulatory duties, a
`drug manufacturer remains primarily responsible for maintaining the adequacy of product
`labeling. State tort law is therefore generally viewed as a complimentary form of drug
`regulation, providing additional protections and recourse for injured consumers. Yet, when
`state tort law imposes a duty impossible to meet in light of FDA regulations, federal law
`will preempt state law.
`II. BACKGROUND
`On November 9, 2015, this Court granted Defendants’ motion for summary
`judgment based on preemption. (Doc. No. 1539.) On appeal, the Ninth Circuit did not reach
`the preemption question, and instead, remanded the case for the Court to permit certain
`discovery, consider the materiality of Plaintiffs’ asserted new safety information, and
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`reinstate the opinion of Plaintiffs’ expert, Dr. Fleming. In re Incretin-Based Therapies
`Prod. Liab. Litig., 721 F. App’x 580, 581–82, 584 (9th Cir. 2017).
`Several years later, and upon completion of supplemental discovery, Defendants
`renewed their joint motion for summary judgment based on preemption. (Doc. No. 3594.)
`In addition, Defendants each filed a motion for summary judgment based on lack of general
`causation as to their respective drugs. 2 (Doc. Nos. 3524, 3525, 3585.) The parties also filed
`motions to exclude certain experts. (Doc. Nos. 3521, 3586, 3613.) On October 20, 2020,
`the Court heard oral arguments on the motions and thereafter took the matter under
`submission.3
`III. LEGAL STANDARD
`Federal Rule of Civil Procedure 56 governs motions for summary judgment.
`Summary judgment permits a court to enter judgment on factually unsupported claims, see
`Celotex Corp. v. Catrett, 477 U.S. 319, 327 (1986), and may also be used on affirmative
`defenses. Dam v. Gen’l. Elec. Co., 265 F.2d 612, 614 (9th Cir. 1958). Granting summary
`judgment is proper if there is “no genuine dispute as to any material fact and the movant is
`entitled to judgment as a matter of law.” Fed. R. Civ. P. 56(a). A fact is material when,
`under the governing substantive law, it could affect the outcome of the case. Anderson v.
`Liberty Lobby, Inc., 477 U.S. 242, 248 (1986). A dispute about a material fact is genuine
`“if the evidence is such that a reasonable jury could return a verdict for the nonmoving
`party.” Id.
`
`
`2 From their briefs, it appears that Amylin and Lilly, who are responsible for Byetta, are jointly defending
`themselves in the instant motions before this Court. Throughout this Order, the Court will take the parties’
`lead and refer primarily to Amylin for simplicity.
`
` 3
`
` Pursuant to the agreement of all parties and in an effort to promote the convenient and efficient resolution
`of nearly identical summary judgment and evidentiary motions pending in the state and federal
`proceedings, the Court held joint oral argument with Judge Highberger of the Los Angeles County
`Superior Court, who is presiding over the pancreatic cancer cases pending in state court (Case No. JCCP
`4272). See In re Phenylpropanolamine (PPA) Products Liab. Litig., 460 F.3d 1217, 1222 (9th Cir. 2006)
`(noting a court’s statutory charge in a multidistrict litigation proceeding is to promote the just and efficient
`conduct of the actions pursuant to 28 U.S.C. § 1407). The Court also participated in a subsequent motion
`hearing before Judge Highberger on December 8, 2020. While these hearings were held jointly, the Court
`has deliberated on the case individually and without discussion of the merits with the state court judge.
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`The moving party has the initial burden of demonstrating that summary judgment is
`proper. See Adickes v. S.H. Kress & Co., 398 U.S. 144, 152 (1970). The burden then shifts
`to the opposing party to provide admissible evidence beyond the pleadings to show that
`summary judgment is not appropriate. See Celotex, 477 U.S. at 322, 324. The court must
`review the record as a whole and draw all reasonable inferences in favor of the non-moving
`party. Hernandez v. Spacelabs Med. Inc., 343 F.3d 1107, 1112 (9th Cir. 2003). However,
`unsupported conjecture or conclusory statements are insufficient to defeat summary
`judgment. Id.; Surrell v. Cal. Water Serv. Co., 518 F.3d 1097, 1103 (9th Cir.2008). “The
`mere existence of a scintilla of evidence in support of the plaintiff’s position will be
`insufficient” to survive summary judgment. Anderson v. Liberty Lobby, Inc., 477 U.S. 242,
`252 (1986). A party opposing summary judgment must come forward with “significant
`probative evidence tending to support its claim that material, triable issues of fact remain.”
`Sanchez v. Vild, 891 F.2d 240, 242 (1989).
`IV. DISCUSSION
`Defendants assert that they are entitled to summary judgment because it is
`impossible to comply with both the FDA’s regulatory scheme and state law failure-to-warn
`requirements, and because there is no genuine dispute of material fact as to general
`causation. Plaintiffs maintain that Defendants have not established preemption, and that
`their experts have established a pathway to causation. Both Plaintiffs and Defendants move
`to exclude certain experts. The Court discusses these motions in turn.
`PREEMPTION MOTION
`A.
`The preemption question before the Court is whether Defendants are entitled to
`summary judgment based on the affirmative defense of federal preemption because it is
`impossible for Defendants to comply with both the FDA’s regulations and the state law
`failure-to-warn requirements upon which Plaintiffs rest their claims.
`1) Relevant Law
`Under the Supremacy Clause of the United States Constitution, “Congress has the
`power to preempt state law.” Crosby v. Nat’l Foreign Trade Council, 530 U.S. 363, 372
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`(2000); see also Oneok, Inc. v. Learjet, Inc., 135 S. Ct. 1591, 1594–95 (2015). “This means
`that when federal and state law conflict, federal law prevails and state law is preempted.”
`Knox v. Brnovich, 907 F.3d 1167, 1173 (9th Cir. 2018) (quoting Murphy v. NCAA, 138 S.
`Ct. 1461, 1476 (2018)). This case concerns impossibility preemption, which is a type of
`conflict preemption that occurs when it is “impossible for a private party to comply with
`both state and federal requirements.” Mutual Pharmaceutical Co. v. Bartlett, 570 U. S.
`472, 480 (2013) (citation omitted).
`In the context of pharmaceutical drugs litigation, the Supreme Court held in Wyeth
`v. Levine that a state law claim that a drug manufacturer failed to warn consumers of a risk
`associated with using its drug is preempted by the FDCA and related labeling regulations,
`if there is “clear evidence” that the FDA would not have approved a change to the drug’s
`label. 555 U.S. 555, 571 (2009). Ten years later in Merck Sharp & Dohme Corp. v.
`Albrecht, the Supreme Court clarified that courts should treat the question of whether clear
`evidence is met “not as a matter of fact for a jury, but as a matter of law for the judge to
`decide.” 139 S. Ct. 1668, 1679 (2019). It did “not further define Wyeth’s use of the ‘clear
`evidence’ in terms of evidentiary standards, such as ‘preponderance of evidence’ or ‘clear
`and convincing evidence.’” Id. Instead, a judge must simply answer the question of
`“whether the relevant federal and state laws ‘irreconcilably conflict.’” Id. (citation
`omitted).
`To that end, the Supreme Court explained that because the FDA’s “changes being
`effected” (“CBE”) regulations permit drug manufacturers to add or strengthen a label
`without prior approval, 21 C.F.R. § 314.70(c)(6)(iii)(A), “a drug manufacturer will not
`ordinarily be able to show that there is an actual conflict between state and federal law such
`that it was impossible to comply with both.” Id. at 1679. However, while a manufacturer
`bears responsibility for maintaining the adequacy of its labels for as long as the drug is on
`the market, it “cannot propose a change that is not based on reasonable evidence.” Id. There
`must be sufficient evidence of a causal association between the drug and the information
`sought to be added. Id. Additionally, the Albrecht court held that “‘clear evidence’ is
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`evidence that shows the court that the drug manufacturer fully informed the FDA of the
`justifications for the warning required by state law and that the FDA, in turn, informed the
`drug manufacturer that the FDA would not approve a change to the drug’s label to include
`that warning.” Id. at 1672.
`2) Whether Federal and State Law “Irreconcilably Conflict”
`Turning to whether federal and state laws irreconcilably conflict, Defendants claim
`that it is impossible to comply with both the FDA’s regulatory scheme and state law
`because (1) Plaintiffs’ alleged “newly acquired information” is not material and does not
`satisfy the requirements of the CBE regulation, and (2) because there is clear evidence that
`the FDA would have rejected a pancreatic cancer warning in the labels for Byetta, Januvia,
`Janumet, and Victoza. Plaintiffs contend that Defendants’ arguments are incompatible with
`the Ninth Circuit’s order in this case, as well as the Supreme Court’s recent decision in
`Albrecht.
`As an initial matter, the Court finds that the Ninth Circuit’s decision in this case does
`not foreclose the entry of summary judgment on preemption. Pertinent here, the Ninth
`Circuit ruled only that the Court should have considered in its earlier preemption analysis
`whether the FDA reviewed Plaintiffs’ new safety information and whether that information
`would be material to the FDA’s conclusion. In re Incretin-Based Therapies Prod. Liab.
`Litig., 721 F. App’x at 582 (finding that the Court should not have “relied on Buckman to
`deem the plaintiffs’ newly discovered evidence ‘irrelevant’ to the court’s preemption
`analysis at the summary judgment stage”). Nothing in the appellate court’s decision
`prevents the Court from conducting that very analysis here. Indeed, Albrecht held that when
`conducting a preemption analysis, a judge may have to resolve contested brute facts, such
`as whether a manufacturer submitted all material information to the FDA because such
`factual questions are part and parcel of the broader legal question and do not warrant
`submission to a jury. 139 S. Ct. at 1681. Thus, the Court will determine whether the FDA’s
`regulatory scheme and state law failure-to-warn requirements “irreconcilably conflict” and
`resolve issues regarding materiality along the way. Id.
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`Plaintiffs also contend that Albrecht limited preemption to cases where the
`manufacturer has proposed a label change. (Doc. No. 3721 at 19).4 The Court, however,
`does not read Albrecht so narrowly. Rather, the Court finds that Albrecht simply reiterated
`the lesson in Wyeth that the availability of the CBE label change process makes it such that
`a manufacturer will not “ordinarily” be able to show an irreconcilable conflict between
`state and federal law. Albrecht, 139 S. Ct. at 1679. Important here, the Supreme Court also
`recognized that this general principle cannot be applied in every case by expressly stating
`that “manufacturers cannot propose a change that is not based on reasonable evidence.” Id.
`(citing 21 C.F.R. § 314.70(c)(6)(iii)(A)). Moreover, the Albrecht court noted: “The
`question of disapproval ‘method’ is not now before us. And we make only the obvious
`point that, whatever the means the FDA uses to exercise its authority, those means must lie
`within the scope of the authority Congress has lawfully delegated.” Id. (emphasis added).
`Further, the manufacturer in Albrecht “conceded that the FDA’s CBE regulation
`would have permitted [it] to try to change the label to add a warning” before the FDA
`required it do so. 139 S. Ct. at 1675. The manufacturers in this case do not make such a
`concession. To the contrary, they maintain that the CBE regulations did not permit them to
`change their labeling because they had no newly acquired information to support the
`change that Plaintiffs propose. As such, the Court finds Albrecht distinguishable in this
`respect. For these reasons, the Court declines to find that Albrecht forecloses preemption
`merely because there was no CBE or other label change request in this case. See, e.g.,
`Cerveny v. Aventis, Inc., 783 F. App’x 804, 808 n.9 (10th Cir. 2019) (rejecting, post
`Albrecht, the plaintiffs’ argument that “only labeling changes sought by the manufacturer
`can lead to preemption”); McGrath v. Bayer HealthCare Pharm. Inc., 393 F. Supp. 3d 161,
`170 (E.D.N.Y. 2019) (similarly distinguishing Albrecht based on the manufacturer’s
`concession in that case).
`
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`4 The pinpoint page citations refer to the ECF-generated page numbers at the top of each filing.
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`Instead, the Court agrees with Defendants that whether federal and state laws
`irreconcilably conflict entails the threshold inquiry of whether there is “newly acquired
`information” to support a CBE submission. See Albrecth, 139 S. Ct. at 1679
`(“[M]anufacturers cannot propose a change that is not based on reasonable evidence.”). If
`the answer is no, then the state law claim is preempted. See, e.g., Knight v. Boehringer
`Ingelheim Pharm., Inc., 984 F.3d 329, 332 (4th Cir. 2021) (finding, post-Albrecht, that
`because the manufacturer did not have “newly acquired information” to unilaterally change
`its label, the state law claim is preempted). If the answer is yes, then the Court considers
`whether there is clear evidence that “the drug manufacturer fully informed the FDA of the
`justifications for the warning required by state law and that the FDA, in turn, informed the
`drug manufacturer that the FDA would not approve a change to the drug’s label to include
`that warning.” Albrecth, 139 S. Ct. at 1672. See also In re Taxotere (Docetaxel) Prod. Liab.
`Litig., No. 16-17039, 2020 WL 7480623, at *9–10 (E.D. La. Dec. 18, 2020) (proceeding
`to the clear evidence question promulgated in Albrecht after finding that the manufacturer
`had newly acquired information to support a CBE change). If the answer to the clear
`evidence question is yes, then the state law claim is preempted. As such, the preemption
`framework provides two potential avenues by which Defendants may establish that federal
`and state laws irreconcilably conflict. The Court analyzes each below.
`“Newly Acquired Information” to Support a CBE Label Change
`
`As previously mentioned, the Supreme Court in Albrecht made clear that, in the
`ordinary case, a drug manufacturer will not be able to show actual conflict between federal
`and state law because of the availability of the CBE regulations. 139 S. Ct. at 1679. This
`case, however, is not an ordinary case. Unlike in Wyeth where the FDA and manufacturer
`“gave no more than passing attention to the issue,” 555 U.S. at 572, the FDA and
`manufacturers here have devoted considerable time and attention to the specific safety
`issue raised by Plaintiffs.5 As such, the Court deems it appropriate to consider the question
`
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`5 The Court incorporates herein its prior analysis in 2015 that this case “is clearly distinguishable from the
`facts presented and found insufficient for preemption in Levine and Gaeta.” (Doc. No. 1539 at 19.)
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`of whether there is “newly acquired information” to support a CBE submission against the
`backdrop of the FDA’s years-long attention to, and evaluation of, the pancreatic safety of
`incretin-based drugs.
`
`a. FDA Monitoring of Incretin-Based Therapies
`By way of background, the FDA approved Byetta (exenatide) in April 2005 and
`Januvia and Janumet (sitagliptin) in 2006 and 2007. The FDA has monitored and reviewed
`the safety of incretin-based therapies with respect to pancreatic cancer for several years. In
`2009, the FDA reviewed its adverse event reporting system database for incidences of
`pancreatic cancer associated with exenatide, sitagliptin, and other anti-diabetics. (Doc. No.
`3594-3 at 206–07.) Upon review, the FDA found that “little inference for risk is appreciated
`from review of spontaneous reports of pancreatic cancer” and concluded that “a causal
`association between exposure to one of these agents and pancreatic cancer is indeterminate
`at this time.” (Id. at 213–14.) Based on its conclusion, the FDA did not make any labeling
`recommendations for exenatide or sitagliptin. (Id. at 214.) A month later, in January 2010,
`the FDA approved Victoza (liraglutide).
`In March 2013, the FDA issued a drug safety communication directly related to the
`pancreatic safety of incretin mimetics. (Id. at 219.) In the communication, the FDA
`announced that it was “investigating reports of possible increased risk of pancreatitis and
`pre-cancerous findings of the pancreas from incretin mimetic drugs for type 2 diabetes.”
`(Id.) It explained that it would “obtain and evaluate” the information underlying the reports,
`as well as “evaluate all available data to further understand this potential safety issue.” (Id.)
`The FDA also stated that it had not concluded that incretin mimetics cause or contribute to
`the development of pancreatic cancer, and advised health care professionals to continue
`following the prescribing recommendations in the drug labeling. (Id.)
`In June 2013, as part of its review of the risk of pancreatic cancer associated with
`incretin mimetics and “to gather and share additional information,” the FDA participated
`in the National Institute of Diabetes and Digestive Kidney Diseases and National Cancer
`Institute’s workshop on Pancreatitis-Diabetes-Pancreatic Cancer. (Id.) At the workshop, an
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`FDA official reaffirmed that adverse event data was “less suitable for detecting relatively
`more common events with long latency periods” such as pancreatic cancer. (Doc. No.
`1163-4 at 94.) Another FDA official commented that incretin-based drugs were not
`associated with “[o]vert pancreatic toxicity or pancreatic neoplasms . . . that would indicate
`a risk to human safety.” (Id. at 89.) The FDA official shared that it “issued a post-marketing
`requirement (PMR) on the sponsors of exenatide, liraglutide, and sitagliptin to conduct a
`pancreatic toxicology study in a rodent model of T2D6,” and that none of the three studies
`that met the PMR criteria “definitively demonstrated a treatment-related adverse effect on
`exocrine histology or proliferation.” (Id.)
`
`Notably, in February 2014, the FDA published an article in the New England Journal
`of Medicine (“NEJM”) titled, “Pancreatic Safety of Incretin Mimetics — FDA and EMA
`Assessment” (“Assessment”). (Doc. No. 3594-3 at 2.) The Assessment was authored by
`four FDA officials and members of the European Medicines Agency (EMA). (Id. at 4.)
`According to the Assessment, the FDA independently completed its “comprehensive
`evaluation[] of a safety signal arising from post-marketing reports of pancreatitis and
`pancreatic cancer in patients using incretin-based drugs.” (Id. at 3.) The FDA’s
`comprehensive evaluation included re-evaluation of more than 250 toxicology studies, as
`well as a review of clinical safety databases and the results of cardiovascular outcome trials
`in patients with type 2 diabetes who were treated with incretin-based drugs. (Id.)
`As to the relevance of adverse event reports of pancreatic cancer, the Assessment
`confirmed that “there are inherent limitations to the ability to establish causal relationships”
`due to the high background rates and long latency period of pancreatic cancer, or a possible
`contribution by type 2 diabetes itself. (Id.) Having “explored multiple streams of data
`pertaining to a pancreatic safety signal associated with incretin-based drugs,” the FDA
`concluded that “assertions concerning a causal association between incretin-based drugs
`and pancreatitis or pancreatic cancer, as expressed recently in the scientific literature and
`
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`6 T2D is an abbreviation for Type 2 diabetes. (Doc. No. 1163-4 at 89.)
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`in the media, are inconsistent with the current data.” (Id.) The FDA further concluded that
`the “current knowledge is adequately reflected in the product information or labeling”
`which contained no reference to pancreatic cancer. (Id.)7
`Then, in March 2014, the FDA formally responded to a citizen petition from 2012,
`which called for the withdrawal of Victoza (liraglutide) from the market, claiming in part
`that Victoza increases the risk of pancreatic cancer and citing FDA Adverse Event
`Reporting System (“FAERS”) data in support. (Doc. No. 3494-4 at 27.) In its response, the
`FDA reiterated that FAERS data “does not provide strong evidence of risk when the
`adverse event (i.e., pancreatic cancer) occurs commonly in the background untreated
`population and has a long latency period.” (Id.) The FDA further stated that in its review
`49 cases recovered from FAERS, it “found no new evidence regarding the risk of
`pancreatic carcinoma in association with the use of Victoza that would support any changes
`to the current approved labeling.” Based on these findings, the FDA made no labeling
`recommendations specific to pancreatic cancer and noted that “[a]ny causal association
`between exposure to Victoza and pancreatic cancer is indeterminate at this time.” (Id.)
`In September 2014, the FDA again considered the pancreatic safety of incretin
`mimetics when it evaluated whether to approve Saxenda, a higher dose of liraglutide
`marketed for weight loss. (Doc. No. 3594-4 at 43.) In the briefing document, the FDA
`noted that “[r]isk for pancreatic cancer has more recently emerged as a concern with
`GLP-1-based therapies, including liraglutide . . . However, animal, observational, and
`clinical trial data reviewed by FDA to date have not supported a causal association.” (Id.
`at 42.) The FDA also referenced its 2014 NEJM Assessment and repeated that it has
`“explored multiple data streams to evaluate pancreatic toxicity as a potential drug safety
`signal” and that such data “do not support pancreatic cancer as an incretin
`mimetic-mediated event.” (Id. at 43.) Three months later, the FDA approved the use of a
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`7 The Assessment was updated in June 2014 to amend the description of incretins in the second sentence
`of the second paragraph. (Doc. No. 3594-3 at 222.) The change is inconsequential to this decision.
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`higher dose of liraglutide for weight management, without requiring a pancreatic cancer
`warning.
`Similarly, in June 2017, the FDA prepared a briefing document for a meeting on a
`proposed new cardiovascular risk reduction indication for liraglutide based on the
`LEADER study, a randomized double-blinded, placebo-controlled cardiovascular
`outcomes trial. (Doc. No. 3594-5 at 87, 92.) In addition to assessing liraglutide’s
`cardiovascular safety, LEADER evaluated its pancreatic safety. (Id. at 93.) According to
`the briefing document, “an FDA Oncology consult team has independently reviewed the
`pancreatic cancer information in LEADER” and “[t]heir overall conclusion is that data
`generated from LEADER do not appear to substantively alter the original FDA conclusions
`regarding the lack of sufficient information to conclusively determine whether long term
`exposure to GLP-RAs increase the risk of pancreatic cancer.” (Id. at 94.) Two months later,
`the FDA approved the cardiovascular risk reduction indication for Victoza.
`Later, in June 2019, the FDA announced that it “approved Victoza (liraglutide)
`injection for treatment of pediatric patients 10 years or older with type 2 diabetes” making
`it “the first non-insulin drug approved to treat type 2 diabetes in pediatric patients since
`metformin was approved for pediatric use in 2000.” (Doc. No. 3594-4 at 576.) Indeed, for
`the last several years, the FDA has approved new incretin-based medications without
`requiring a reference to pancreatic cancer in their labels. Notably, the FDA has also
`approved various labeling changes for Defendants’ drugs since their initial approval—the
`most recent of which was in June 2019 for liraglutide, August 2019 for sitagliptin, and
`February 2020 for exenatide. Despite their close monitoring and comprehensive evaluation
`of the pancreatic safety of incretin-based therapies, the FDA has never required Defendants
`to include a pancreatic cancer warning in their drug labeling.
`Guided by Wyeth v. Levine and the record before it in November 2015, this Court
`granted Defendants’ first motion for summary judgment based on preemption, holding that
`“Defendants have demonstrated by clear evidence that the FDA would have rejected a
`reference to pancreatic cancer in the product labeling during the time in which Plaintiffs’
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`claims accrued.” (Doc. No. 1539 at 34.) In so holding, the Court relied on the February
`2014 NEJM Assessment and the FDA’s March 2014 formal rejection of the citizen petition
`requesting withdrawal of Victoza—both of which “falls squarely within the FDA’s
`congressionally delegated authority to regulate the safety of prescription drugs” (id. at 25),
`and communicated that a causal association between incretin-based drugs and pancreatic
`cancer is not supported by the FDA’s review of the data (id. at 18–19).
`Although the Court’s decision was appealed, the Ninth Circuit did not consider the
`Court’s preemption findings and remanded the case for other reasons. In re Incretin-Based
`Therapies Prod. Liab. Litig., 721 F. App’x at 581–82. And as Albrecht did not create new
`preemption law, but rather, merely elaborated on Wyeth, the Court reaffirms its 2015
`findings that the record at that time:
`establishe[d] the FDA has specifically considered pancreatic cancer risk,
`commented publicly on the adequacy of drug labeling, and maintained its
`position that scientific evidence of a causal association between incretin
`mimetics and pancreatic cancer is indeterminate. Because an indeterminate
`causal association falls below the federal regulatory standards required for
`labeling changes, clear evidence exists that the FDA would have rejected a
`reference to pancreatic cancer in product labeling.
`(Doc. No. 1539 at 2.) Consequently, with this particular regulatory and procedural
`backdrop in mind, the Court conside