Plexxikon Inc. v. Novartis Pharmaceuticals Corporation

Filing 422

ORDER by Judge Haywood S. Gilliam, Jr. GRANTING IN PART AND DENYING IN PART 204 MOTION TO EXCLUDE THE EXPERT TESTIMONY OF SUSANA ORTIZ-URDA. (ndrS, COURT STAFF) (Filed on 5/26/2020)

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1 2 3 4 UNITED STATES DISTRICT COURT 5 NORTHERN DISTRICT OF CALIFORNIA 6 7 PLEXXIKON INC., Plaintiff, 8 v. 9 10 11 NOVARTIS PHARMACEUTICALS CORPORATION, Case No. 17-cv-04405-HSG ORDER GRANTING IN PART AND DENYING IN PART MOTION TO EXCLUDE THE EXPERT TESTIMONY OF SUSANA ORTIZ-URDA Re: Dkt. No. 204 United States District Court Northern District of California Defendant. 12 13 Pending before the Court is Defendant Novartis Pharmaceuticals Corporation’s motion to 14 exclude the testimony of Plaintiff Plexxikon Inc.’s expert Susana Ortiz-Urda. Dkt. No. 204. The 15 Court heard argument on this motion on November 1, 2019. See Dkt. No. 341. As detailed 16 below, the Court GRANTS IN PART and DENIES IN PART the motion. 17 18 I. BACKGROUND Defendant challenges the testimony of Plaintiff’s clinical expert, Dr. Susana Ortiz-Urda, as 19 speculative and not based on any reliable methodology. Dkt. No. 204. In her expert report, Dr. 20 Ortiz-Urda offers opinions about the treatment of melanoma, its evolution, and how physicians 21 would respond in the hypothetical scenario in which Defendant’s drug Tafinlar was not available 22 as a combination therapy with Mekinist. See Dkt. No. 227-2 (“Ortiz-Urda Report”). 23 Dr. Ortiz-Urda explains that both immunotherapies and targeted therapies are widely 24 prescribed for the treatment of metastatic melanoma. See id. at ¶ 57. However, she explains that 25 there are some circumstances in which targeted therapies are more appropriate for certain 26 BRAFV600E metastatic melanoma patients. See id. at ¶¶ 57–62. There are only a few such 27 targeted therapies currently available. See id. at ¶ 62. The combination of Tafinlar and Mekinist 28 became the first combination therapy to be approved for the treatment of metastatic melanoma in 1 January 2014. See id. at ¶ 43. In November 2015, Plaintiff’s Zelboraf drug was approved by the 2 Food and Drug Administration (“FDA”) in combination with Cotellic. See id. at ¶ 48. The FDA 3 then approved a third combination therapy, Braftvoi and Mektovi, in June 2018. Id. at ¶ 50. Dr. 4 Ortiz-Urda states that these combination therapies, as opposed to monotherapies, have become the 5 standard of care for patients with metastatic melanoma. Id. at ¶ 51. She clarifies that in her 6 experience, physicians often prescribe the Tafinlar-Mekinist combination therapy because they are 7 more familiar with it as the first to market, but not because it “is superior from a therapeutic 8 perspective” to the other combination therapies. Id. at ¶ 63. In a single paragraph, Dr. Ortiz-Urda 9 also notes that the Tafinlar–Mekinist combination therapy is approved for the treatment of certain 10 other cancers for which the Zelboraf–Cotellic combination is not approved. See id. at ¶ 72. Dr. Ortiz-Urda then offers two primary opinions regarding a hypothetical world in which United States District Court Northern District of California 11 12 the Taflinar-Mekinist combination was not an option for treating physicians: (1) BRAFV600E 13 metastatic melanoma patients who were prescribed the combination therapy of Tafinlar and 14 Mekinist would be prescribed another targeted therapy, including Plaintiff’s Zelboraf drug in 15 combination with Cotellic; and (2) also that “some percentage of prescribing physicians would 16 prescribe the Zelboraf–Cotellic combination off label to patients for indications for which 17 Tafinlar–Mekinist is approved but the Zelboraf–Cotellic combination is not.” Id. at ¶ 6(a)–(b); see 18 also id. at ¶¶ 66–68, 72. In particular, in addition to metastatic melanoma, Dr. Ortiz-Urda notes 19 that the Tafinlar–Mekinist combination is approved by the FDA for the treatment of non-small cell 20 lung cancer and metastatic anaplastic thyroid cancer. Id. at ¶ 72. Although the Zelboraf–Cotellic 21 combination is not approved for the treatment of these cancers, Dr. Ortiz-Urda opines that 22 “physicians would reasonably conclude” that it would be effective against them and prescribe 23 them anyway as they have a similar “mechanism of action” to the Tafinlar–Mekinist combination. 24 See id. Dr. Ortiz-Urda repeated similar opinions in her reply report. See Dkt. No. 227-4, Ex. 3 25 (“Ortiz-Urda Reply Report”). 26 27 28 II. LEGAL STANDARD Federal Rule of Evidence 702 allows a qualified expert to testify “in the form of an opinion or otherwise” where: 2 1 (a) the expert’s scientific, technical, or other specialized knowledge will help the trier of fact to understand the evidence or to determine a fact in issue; (b) the testimony is based on sufficient facts or data; (c) the testimony is the product of reliable principles and methods; and (d) the expert has reliably applied the principles and methods to the facts of the case. 2 3 4 Fed. R. Evid. 702. Expert testimony is admissible under Rule 702 if it is both relevant and 6 reliable. See Daubert v. Merrell Dow Pharm., Inc., 509 U.S. 579, 597 (1993). “[R]elevance 7 means that the evidence will assist the trier of fact to understand or determine a fact in issue.” 8 Cooper v. Brown, 510 F.3d 870, 942 (9th Cir. 2007); see also Primiano v. Cook, 598 F.3d 558, 9 564 (9th Cir. 2010) (“The requirement that the opinion testimony assist the trier of fact goes 10 primarily to relevance.”) (quotation omitted).1 Under the reliability requirement, the expert 11 United States District Court Northern District of California 5 testimony must “ha[ve] a reliable basis in the knowledge and experience of the relevant 12 discipline.” Primiano, 598 F.3d at 565. To ensure reliability, the Court “assess[es] the [expert’s] 13 reasoning or methodology, using as appropriate such criteria as testability, publication in peer 14 reviewed literature, and general acceptance.” Id. at 564. 15 III. DISCUSSION Defendant contends that as a dermatologist and melanoma specialist at the University of 16 17 California at San Francisco (“UCSF”) Melanoma Center, Dr. Ortiz-Urda is unaware of the 18 behavior of prescribing physicians outside of her own practice group at UCSF. See Dkt. No. 204 19 at 7–9. Defendant thus seeks to preclude her testimony about how physicians outside UCSF 20 would respond in the hypothetical world in which Tafinlar and Mekinist were not available. Id. 21 The Court addresses Defendant’s argument as it pertains to each of Dr. Ortiz-Urda’s opinions 22 about prescription practices for: (1) metastatic melanoma; and (2) other cancers. 23 A. 24 First, Dr. Ortiz-Urda opines that if Tafinlar and Mekinist were not available, metastatic 25 melanoma patients who were prescribed this combination therapy would be prescribed another Prescription Practices for Metastatic Melanoma 26 27 28 Whether to admit expert testimony is evaluated “under the law of the regional circuit,” so in this case, under the law of the Ninth Circuit. See Micro Chem., Inc. v. Lextron, Inc., 317 F.3d 1387, 1391 (Fed. Cir. 2003). 3 1 1 2 targeted therapy. See Ortiz-Urda Report at ¶¶ 57–62. Defendant does not argue that Dr. Ortiz-Urda is unqualified to offer opinions about the treatment of melanoma. Rather, Defendant contends that her opinions about what physicians 4 would do without Tafinlar and Mekinist are wholly speculative because during her deposition, Dr 5 Ortiz-Urda acknowledged that she is “less familiar” with the prescribing practices of physicians 6 outside of UCSF. See id. at 7 (citing Dkt. No. 204-4, Ex. 3 (“Ortiz-Urda Depo.”) at 51:3–52:5; 7 150:17–151:12). She also explained that prescribing practices may differ based on physicians’ 8 perception of side effects and their own clinical experiences. See id. (citing Ortiz-Urda Depo. at 9 31:19–25; 42:24–43:12; 90:13–19). Defendant also points out that Dr. Ortiz-Urda did not engage 10 in any systematic analysis outside her own firsthand experience to obtain information about other 11 United States District Court Northern District of California 3 physicians’ practices. See id. at 5, 7–8. 12 The Court is not persuaded that these statements from Dr. Ortiz-Urda’s deposition taken 13 together render her opinions speculative and unreliable. Neither Daubert nor Rule 702 requires 14 experts to conduct 50-state surveys before they may offer opinions about the standard of care. 15 Rather, the Supreme Court has cautioned that the Daubert inquiry is intended to be flexible, and 16 when evaluating specialized or technical expert opinion testimony, “the relevant reliability 17 concerns may focus upon personal knowledge or experience.” See Kumho Tire Co. v. 18 Carmichael, 526 U.S. 137, 150 (1999). The Ninth Circuit has recognized that this is particularly 19 true in the medical context: 20 21 22 23 24 25 Despite the importance of evidence-based medicine, much of medical decision-making relies on judgment—a process that is difficult to quantify or even to assess qualitatively. Especially when a relevant experience base is unavailable, physicians must use their knowledge and experience as a basis for weighing known factors along with the inevitable uncertainties to mak[e] a sound judgment. Primiano, 598 F.3d at 565 (quotations omitted). Here, Dr. Ortiz-Urda’s opinions about what metastatic melanoma patients would be 26 prescribed without Tafinlar and Mekinist is based on her “more than ten years of clinical 27 experience treating patients for melanoma,” including with the use of targeted therapies such as 28 4 1 Zelboraf, Cotellic, Tafinlar, and Mekinist, and other immunooncology drugs.2 See Ortiz-Urda 2 Report at ¶ 1. She also helped create a multidisciplinary melanoma program at UCSF, in which 3 she incorporated her research and clinical experience. See id. at ¶ 3. Dr. Ortiz-Urda’s expert 4 report acknowledges that no head-to-head studies have been done comparing Zelboraf to Tafinlar 5 as monotherapies, or comparing the Tafinlar–Mekinist combination with the Zelboraf–Cotellic 6 combination. See id. at ¶ 63. Nevertheless, she cites documents and studies about the relative 7 efficacy and side effects of the available treatments. See id. at ¶¶ 43, 47–51, 63–68. She explains 8 that in her experience physicians prescribe Tafinlar–Mekinist with more frequency than the other 9 combination therapies because it was the first to market, rather than because of a distinction in its therapeutic benefits. See id. at ¶ 63. Dr. Ortiz-Urda also explains why, from a clinical 11 United States District Court Northern District of California 10 perspective, some patients require targeted therapies as opposed to immunotherapies. Id. at ¶¶ 57– 12 62. And during her deposition, Dr. Ortiz-Urda explained that her understanding of how patients 13 would be treated if the Tafinlar–Mekinist combination were unavailable was premised not only on 14 her years of experience and published data, but also on conversations she has had with other 15 physicians outside UCSF. See Ortiz-Urda Depo. at 51:17–52:5. 16 As the Ninth Circuit has acknowledged, “[l]ack of certainty is not, for a qualified expert, 17 the same thing as guesswork.” Primiano, 598 F.3d at 565. Rather, expert opinion testimony “is 18 reliable if the knowledge underlying it has a reliable basis in the knowledge and experience of the 19 relevant discipline.” Id. For purposes of this Daubert motion, the Court finds that Dr. Ortiz-Urda 20 is qualified and has sufficient expertise in the treatment of metastatic melanoma for her testimony 21 about the treatment of metastatic melanoma to be useful to the jury. She has provided sufficient 22 support for her opinions about what she believes to be the standard of care as well as what 23 treatment options and other considerations a prescriber such as herself would have in the 24 25 26 27 28 2 To the extent Defendant suggests that the Court cannot consider the content of Dr. Ortiz-Urda’s expert report in evaluating Defendant’s Daubert motion, see Dkt. No. 243 at 1, that argument is frivolous. The only case Defendant cites, Hunt v. City of Portland, 599 F. App’x 620, 621 (9th Cir. 2013), is inapposite. There, the Ninth Circuit concluded that it was error for the district court to admit an expert report at trial because it constituted hearsay to which no hearsay exception applies. Defendant does not cite, and the Court is not aware, of any case that limits the Court’s Daubert analysis to deposition excerpts. 5 1 2 counterfactual world where the Tafinlar–Mekinist combination was unavailable. To the extent Defendant disagrees with Dr. Ortiz-Urda’s opinions, Defendant may present 3 its own evidence at trial. See Daubert, 509 U.S. at 596 (“Vigorous cross-examination, 4 presentation of contrary evidence, and careful instruction on the burden of proof are the traditional 5 and appropriate means of attacking shaky but admissible evidence.”). As Defendant’s own 6 authority notes, “Daubert makes the district court a gatekeeper, not a fact finder.” See United 7 States v. Sandoval-Mendoza, 472 F.3d 645, 654 (9th Cir. 2006). The jury will ultimately have to 8 decide how persuasive Dr. Ortiz-Urda’s counterfactual testimony is. At this stage, the Court finds 9 that Dr. Ortiz-Urda may testify about the standard of care for metastatic melanoma and, based on this, how she thinks that standard of care would change and adapt were the Tafinlar–Mekinist 11 United States District Court Northern District of California 10 combination no longer available on the market for treating metastatic melanoma. 12 B. 13 Second, Dr. Ortiz-Urda opines that if Tafinlar and Mekinist were not available, “physicians Off Label Prescription Practices for Other Cancers 14 would reasonably conclude that the Zelboraf–Cotellic combination would be effective against” 15 cancers for which the Tafinlar–Mekinist combination is approved, but for which the Zelboraf– 16 Cotellic combination is not approved. See Ortiz-Urda Report at ¶¶ 69–72. Defendant again 17 contends that Dr. Ortiz-Urda’s opinions are speculative and not based on a reliable methodology 18 as she lacks knowledge of how prescribing physicians would behave in this counterfactual world. 19 See Dkt. No. 204. In reply, Defendant clarifies that this speculation is particularly acute for Dr. 20 Ortiz-Urda’s opinions about off-label use of Zelboraf and Cotellic because Dr. Ortiz-Urda is not 21 an oncologist and does not treat patients for non-small cell lung cancer or anaplastic thyroid 22 cancer. See Dkt. No. 243 at 3, 7. 23 Plaintiff offers little explanation why Dr. Ortiz-Urda should be permitted to testify about 24 physicians’ likely behavior when treating cancers other than metastatic melanoma. See Dkt. No. 25 227; see also Dkt. No. 341 at 89:15–94:6. Plaintiff instead responds that Dr. Ortiz-Urda’s opinion 26 remains reliable because it is premised on the fact that Tafinlar–Mekinist and Zelboraf-Cotellic 27 have “the same mechanism of action.” See Ortiz-Urda Report at ¶ 72. During her deposition, Dr. 28 Ortiz-Urda further explained that off-label use is more prevalent in the treatment of terminal 6 1 diseases where “the patient doesn’t have a lot of choices[] and they are running out of time.” See 2 Ortiz-Urda Depo. at 149:16–150:5. Plaintiff also notes that Defendant’s own expert does not 3 challenge Dr. Ortiz-Urda’s opinion that off-label use of drugs exists, only its likely frequency in 4 the case of Zelboraf and Cotellic. See Dkt. No. 227 at 3. However, Dr. Ortiz-Urda does not proffer any data on the prevalence or efficacy of the off- 5 6 label use of Zelboraf or Cotellic, as monotherapies or in combination. To the contrary, she 7 acknowledges that “the prevalence of off-label use focusing on targeted therapies has not been 8 investigated in detail.” See Ortiz-Urda Report at ¶ 71. Moreover, she acknowledged in her 9 deposition that “[i]t’s not true as a general matter that all drugs with the same mechanism of action are clinically equivalent to each other” and “sometimes drugs that have the same mechanism of 11 United States District Court Northern District of California 10 action may be effective for different indications.” See Ortiz-Urda Depo. at 149:3-15. In short, Dr. 12 Ortiz-Urda has not provided any facts or data that would raise her opinion about the likelihood of 13 off-label use of Zelboraf and Cotellic beyond a speculative level. And unlike her opinions about 14 the treatment of metastatic melanoma discussed in Section III.A above, her experience cannot fill 15 the gaps here, as she appears to lack any experience in the treatment (off label or otherwise) of 16 non-small cell lung cancer or anaplastic thyroid cancer. As Dr. Ortiz-Urda explains, “[t]he goal of 17 off-label prescribing is to offer a patient an alternative treatment in the absence of a suitable 18 licensed therapy or a lack of clinical trial access.” See Ortiz-Urda Report at ¶ 71. However, she 19 offers no information about the availability of suitable alternative therapies for other cancers such 20 as non-small cell lung cancer or anaplastic thyroid cancer were Tafinlar and Mekinist unavailable. 21 Thus, Dr. Ortiz-Urda may not testify about whether and to what extent prescribing 22 physicians would prescribe the Zelboraf–Cotellic combination off label to patients for indications 23 for which Tafinlar–Mekinist is approved but the Zelboraf–Cotellic combination is not. 24 IV. 25 CONCLUSION Accordingly, the Court GRANTS IN PART and DENIES IN PART the motion. Dr. 26 Ortiz-Urda may testify from her own experience about the standard of care for the treatment of 27 metastatic melanoma patients and how she would anticipate patients’ treatment changing were 28 Tafinlar and Mekinist not available for metastatic melanoma treatment. However, Dr. Ortiz-Urda 7 1 is precluded from offering testimony about whether and to what extent she would anticipate 2 physicians would prescribe the Zelboraf–Cotellic combination for the treatment of any other 3 indications outside metastatic melanoma, including off-label use for the treatment of non-small 4 cell lung cancer and metastatic anaplastic thyroid cancer. 5 6 7 8 IT IS SO ORDERED. Dated: 5/26/2020 ______________________________________ HAYWOOD S. GILLIAM, JR. United States District Judge 9 10 United States District Court Northern District of California 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 8

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