Butler v. Juno Therapeutics, Inc.
| Decision Date | 21 June 2019 |
| Docket Number | CIVIL ACTION NO. H-18-898 |
| Parties | LISA GAYLE BUTLER and DAVID A. HOLLAND, individually and as personal Representatives of the ESTATE OF MATY GAYLE HOLLAND, deceased. Plaintiffs, v. JUNO THERAPEUTICS, INC. Defendant. |
| Court | U.S. District Court — Southern District of Texas |
Maty Gayle Holland died in 2016, at age 19. She had battled leukemia off and on for six years before she died. She died less than two months after starting to participate in a clinical trial of a drug for FDA approval. (Docket Entry No. 41). After her death, Holland's parents, Lisa Gayle Butler and David A. Holland, individually and as estate representatives, sued the drug manufacturer, Juno Therapeutics, Inc., in March 2018. (Docket Entry No. 1). In October, the plaintiffs filed an amended complaint, and Juno moved to dismiss. (Docket Entry Nos. 41, 43). The plaintiffs responded, Juno replied, and the parties supplemented their briefs on the plaintiffs' fraud allegations and on Juno's learned-intermediary doctrine defense. (Docket Entry Nos. 46, 48, 56-60, 62-1). The court heard oral argument on the motion to dismiss.
Based on the pleadings; the motion, response, and reply; the supplemental briefing; counsels' arguments at the motion hearing; and the applicable law, the court denies the motion to dismiss. (Docket Entry No. 43). The reasons for this decision are detailed below.
In 2010, Holland, then 13-years old, was diagnosed with acute lymphoblastic leukemia. (Docket Entry No. 41 at ¶ 49). Conventional chemotherapy led to remission by the time she entered high school, but the cancer returned during her freshman year of college. (Id. at ¶¶ 49-50). Chemotherapy initially seemed to work, but further rounds did not lead to remission. (Id. at ¶ 50). In May 2016, Holland, then 19-years old, joined Juno's Phase II JCAR015 ROCKET Trial. (Id. at ¶¶ 52, 57). In June, a week after her first infusion of the trial drug, JCAR015, Holland died. (Id. at ¶¶ 76, 80).
The Food and Drug Administration must approve New Drug Applications before a manufacturer may market a drug. 21 U.S.C. § 355(b)(1). The FDA requires three clinical trial phases to show that the drug is efficacious and safe, consistent with the Food, Drug and Cosmetic Act of 1938 before a manufacturer can submit a New Drug Application. Id. § 355(i), (b)(1).
Phase I studies "determine the metabolism and pharmacologic actions of the drug in humans, the side effects associated with increasing doses, and[] . . . early evidence on effectiveness." 21 C.F.R. § 312.21(a). Phase II studies "include[] controlled clinical studies conducted to evaluate the effectiveness of the drug for a particular indication or indications in patients with the disease or condition under study and to determine the common short-term side effects and risks associated with the drug." Id. § 312.21(b). Phase III studies involve "expanded controlled and uncontrolled trials . . . . performed after preliminary evidence suggesting effectiveness of the drug has been obtained." Id. at § 312.21(c). They give new data on the drug's efficacy and safety and help inform physician labeling. Id.
Clinical-trial sponsors must submit an Investigational New Drug Application to the FDA to begin a clinical trial. 21 U.S.C. § 355(i); 21 C.F.R. § 312.20. Sponsors must select medical investigators for the trial and ensure that the investigations are conducted properly and that the "FDA and all participating investigators are promptly informed of significant new adverse effects or risks with respect to the drug." Id. § 312.50. If the three-phase clinical trial is successful in showing the drug's safety and efficacy, the sponsor may file a New Drug Application that specifies the conditions the drug will treat and in what dose. (See Docket Entry No. 41 at ¶¶ 19-23); see 21 U.S.C. § 355(b)(1); 21 C.F.R. §§ 314.50(d)(5).
Before an investigation or clinical trials begin, a sponsor must provide "each participating clinical investigator an investigator brochure," 21 C.F.R. § 312.55(a), containing "[a] brief description of the drug substance and the formulation," "[a] summary of the pharmacological and toxicological effects of the drug in animals and, to the extent known, in humans," "[a] summary of the pharmacokinetics and biological disposition of the drug in animals and, if known, in humans," "[a] summary of information relating to safety and effectiveness in humans obtained from prior clinical studies," and "[a] description of possible risks and side effects to be anticipated on the basis of prior experience with the drug under investigation or with related drugs, and of precautions or special monitoring to be done as part of the investigational use of the drug." 21 C.F.R. § 312.23(a)(5). The sponsor has an ongoing responsibility to Id. § 312.55(b).
Testing new drugs on people, even people with few options, is fraught with ethical issues. Those are amplified when the patient is young. The regulations address the ethical concerns byrequiring informed consent after the risks are properly disclosed. "[N]o investigator may involve a human being as a subject in research . . . unless the investigator has obtained the legally effective informed consent of the subject or the subject's legally authorized representative." Id. § 50.20. Disclosures required for legally effective informed consent include, among other things, "[a] description of any reasonably foreseeable risks or discomforts to the subject" and, "[f]or research involving more than minimal risk . . . and an explanation as to whether any medical treatments are available if injury occurs and, if so, what they consist of, or where further information may be obtained." Id. § 50.25(a)(2), (6).
One critical issue in this case is whether Juno adequately disclosed the risks to Holland to satisfy the requirements for legally sufficient informed consent. Another issue is whether the fact that Juno paid the JCAR015 ROCKET Trial investigator to conduct the Trial vitiates the learned-intermediary doctrine. These and other issues raised by the motion to dismiss and response are analyzed below.
Juno Therapeutics develops biopharmaceutical "cellular immunotherapies" for treating cancer. (Docket Entry No. 41 at ¶ 1). Juno specializes in treatments that collect, modify, and use a patient's own T cells to treat that patient's cancer. (Id.). The most advanced of these treatments is CAR-T therapy. (Id.).
Juno sponsors clinical trials to test its products. (Id.). Juno has three "CD19 Product Candidates, JCAR014, JCAR015, and JCAR017. All "use a chimeric antigen receptor" or "CAR" to target the CD19 protein found on the surface of the malignant white blood cells that cause B-cell leukemia and lymphoma. (Id.). The CAR-T therapy using these products begins with leukapheresis, or harvesting of the patient's own white blood cells. (Id. at ¶ 15). Once harvested,the T cells are "selected and activated," and "gene sequences for the CAR construct are transferred into the T cell DNA using a viral vector." (Id.). This process creates receptors on the T-cell surface that, once infused back into the patient's body, allow the T cells to recognize and attack the CD19 protein on the cancer cells. (Id. at ¶ 14). The number of modified cells is then expanded to the proper dose. (Id. at ¶ 15). The patient receives chemotherapy to deplete the existing T cells and allow the modified cells to grow. (Id. at ¶ 16). The last step is to infuse the patient with the genetically engineered T cells. (Id. at ¶ 17).
The FDA has not yet approved any of Juno's CD19 product candidates. None of its CD19 products has made it past a Phase II clinical trial. (Id. at ¶ 2).
Juno competes with other biotech companies to enroll patients in clinical drug trials so that it can be the first to the market with a CAR-T immunotherapy that makes it through the FDA approval process. (Id. at ¶ 3). Juno used a "fast to market strategy" for JCAR015 and designated the JCAR015 Phase II trial as a "ROCKET Trial." (Id.). In its 2015 Annual Report, Juno stated that it planned to seek regulatory approval for JCAR015 as early as 2017. (Id.). The Annual Report warned of delay if Juno had trouble enrolling patients in its clinical trials and identified the treatment-related side effects as a possible barrier to enrollment. (Id. at ¶¶ 4,5).
In January 2007, the Memorial Sloan Kettering Cancer Center in New York sponsored an Investigational New Drug Application for Juno's JCAR015. (Id. at ¶ 31). The Phase I clinical trial began in January 2010 and was expected to end in January 2017. Early results showed that JCAR015 had serious risks. (Id. at ¶¶ 31-33). In its 2015 Annual Report, Juno acknowledged side effects ranging from "minor reactions to death," including severe neurotoxicity severecytokine release syndrome.1 (Id. at ¶¶ 6, 33). Both neurotoxicity and severe cytokine release syndrome require "ICU level care" and can be fatal. (Id. at ¶¶ 28, 35).
The FDA placed the JCAR015 ROCKET Trial on hold after two patients died in 2014. (Id. at ¶ 36). The FDA removed the hold after Juno made several changes to the Phase I protocol. (Id.) According to Juno's 2015 Annual Report, 52% of the patients in the Trial with acute lympoblastic leukemia suffered from either severe cytokine release syndrome or severe neurotoxicity. (Id. at ¶ 38). In the "morphologic patient population" of the patients with more than 5% lymphoblasts in their bone marrow, 84% suffered from either severe cytokine release syndrome or severe neurotoxicity. (Id. at ¶ 39). Juno stated in 2015 that besides the severe cytokine release syndrome or...
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