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`CIVIL ACTION NUMBER:
` 11-3962
`
` TRIAL
`
` UNITED STATES DISTRICT COURT
` FOR THE DISTRICT OF NEW JERSEY
`__________________________________
`HELSINN HEALTHCARE, S.A. and
`ROCHE PALO ALTO, LLC,
` Plaintiffs,
` -vs-
`DR. REDDY'S LABORATORIES, LTD.,
`DR. REDDY'S LABORATORIES, INC.,
`TEVA PHARMACEUTICALS USA, INC.,
`and TEVA PHARMACEUTICAL
`INDUSTRIES, LTD.
` Defendants.
`__________________________________
` Clarkson S. Fisher United States Courthouse
` 402 East State Street
` Trenton, New Jersey 08608
` June 11, 2015
`B E F O R E: THE HONORABLE MARY L. COOPER
`
`UNITED STATES DISTRICT JUDGE
`
`Certified as True and Correct as required by Title 28, U.S.C.,
`Section 753
`
`/S/ Regina A. Berenato-Tell, CCR, CRR, RMR, RPR
`/S/ Carol Farrell, CCR, CRR, RMR, CCP, RPR, RSA
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`United States District Court
`Trenton, New Jersey
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`Helsinn Healthcare Exhibit 2009
`Dr. Reddy's Laboratories, Ltd., et al. v. Helsinn Healthcare S.A.
`Trial PGR2016-00008
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`Page 1 of 5
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`A P P E A R A N C E S:
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`PAUL HASTINGS
`BY: JOSEPH O'MALLEY, ESQUIRE
`SAUL EWING
`BY: CHARLES M. LIZZA, ESQUIRE
`Attorneys for the Plaintiffs
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`BUDD LARNER
`BY: STUART D. SENDER, ESQUIRE
`Attorneys for the Defendant, Dr. Reddy's Laboratories
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`WINSTON & STRAWN
`BY: JOVIAL WONG, ESQUIRE
` GEORGE LOMBARDI, ESQUIRE
` JULIA MANO JOHNSON, ESQUIRE
` BRENDAN F. BARKER, ESQUIRE
`LITE DePALMA, GREENBERG, LLC
` BY: MAYRA V. TARANTINO, ESQUIRE
`Attorneys for the Defendant, Teva
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`United States District Court
`Trenton, New Jersey
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`I N D E X
`
`WITNESS VOIR DIRECT CROSS REDIRECT RECROSS
` DIRE
`CARL CURTIS PECK
`By Mr. O'Malley 5 20 175
`By Lombardi 80 184
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`Colloquy
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`4
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` (In open court. June 11, 2015, 9:30 a.m.)
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`THE COURT: Good morning, all.
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`ALL: Good morning, your Honor.
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`THE COURT: Mr. O'Malley.
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`MR. O'MALLEY: Good morning. Your Honor, before we
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`call our next witness, just a minor housekeeping item. From
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`Dr. Candiotti yesterday, I believe we gave the court clerk a
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`list of his exhibits, but I don't think we moved them into
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`evidence. I have another copy of that list, if need be.
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`So, I just would like to move those exhibits into
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`evidence.
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`THE COURT: Has the other side seen it?
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`MR. LOMBARDI: We'd just like -- we haven't seen the
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`actual list that he's tendering, so we'd just like to see it.
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`I don't anticipate any issues.
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`MR. O'MALLEY: It's just the exhibits that were --
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`MR. LOMBARDI: I don't anticipate an issue.
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`THE COURT: Okay. After the break then, you can move
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`it in, Mr. O'Malley. All right?
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`MR. O'MALLEY: So with that, your Honor, we would
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`like to call our next witness Dr. Carl Peck.
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`(Whereupon, CARL CURTIS PECK, witness for the
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`Plaintiffs, sworn.)
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`THE DEPUTY CLERK: Please state and spell your full
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`name for the record.
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`United States District Court
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`Trenton, New Jersey
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`Peck - Direct
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`Have a seat.
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`THE WITNESS: Carl Curtis Peck.
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`5
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`MR. O'MALLEY: If I may approach, your Honor. I have
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`the witness' exhibits. We've already distributed copies to
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`the Court.
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`VOIR DIRE EXAMINATION BY MR. O'MALLEY:
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`Q.
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`A.
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`Q.
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`Good morning, Dr. Peck.
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`Good morning.
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`Dr. Peck, could you please turn to Plaintiffs' Trial
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`Exhibit 183.
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`Do you recognize this document?
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`I do.
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`For the benefit of the Court, can you briefly describe
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`A.
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`Q.
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`your educational background after high school?
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`A.
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`So, I spent three years at the University of Kansas in
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`Lawrence and received a degree in mathematics and chemistry.
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`Following that, I took a Fulbright year in Germany
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`studying physical chemistry at the University of Tübingen and
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`the Technische Hochschule in Stuttgart.
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`Q.
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`You may have to spell that, Dr. Peck. Do you have it?
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`Never mind.
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`And go on.
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`A.
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`Well, thereafter, I went back to Lawrence -- or to Kansas
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`and attended medical school.
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`Q.
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`Okay. And did you earn a medical degree?
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`Peck - Direct
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`Peck - Direct
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`THE COURT: I think maybe this would be a good time
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`for a break.
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`MR. O'MALLEY: Perfect. Your Honor. Thank you.
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`(Brief Recess.)
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`THE COURT: Thank you.
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`BY MR. O'MALLEY:
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`Q.
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`Dr. Peck, did you hear Dr. Fruehauf provide some
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`testimony regarding the results of Helsinn's Phase II 2330
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`study?
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`A.
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`Q.
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`I did.
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`Let's take a look at Defendants' Trial Exhibit 227. It's
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`in one of the smaller separate notebooks in front of you. It
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`will also be on the screen in front of you. What is this
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`document?
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`A.
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`So, this is the front page of the clinical section of the
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`NDA, Item 8, and this content identifies the 2330 study report
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`which will follow in Volume 104.
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`Q.
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`And let's look at Defendants' Trial Exhibit 227-0005,
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`near the bottom of the page. What do those dates indicate at
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`the bottom of that page?
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`A.
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`Right. So this is standard report -- reporting of
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`certain milestones in the performance of a clinical trial,
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`where the study date was started in May of 1994, the study
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`date was completed on April 1995, meaning the last patient
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`out, and the date of the report is July 1995.
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`A.
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`Well, there were five dose groups that were administered.
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`As you can see, they range from .3 to 90 micrograms per
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`kilogram of body weight. There were a total of 161 patients.
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`24 patients were in the 3-microgram-per-kilogram group, a
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`group of particular interest, but about the same number of
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`patients were in each -- each of the others.
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`Most of the subjects were male. None of them had
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`received a chemotherapeutic agent before, and basically, it
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`was a small study that was quite unrepresentative of any, you
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`know, broader population.
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`Q.
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`And, by way of summary, what were the results of this
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`study?
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`A.
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`Well, I think we're going to see a richer table, but --
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`but there was the identification of one dose group, the
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`30-microgram-per-kilogram group, that yielded a statistically
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`significant difference or finding for one of the outcome
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`measures called complete control after 24 hours.
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`Q.
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`Okay. Now, as you noted, we're going to dig into the
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`details in a moment.
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`Were there any conclusions that could be drawn from
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`Study 2330 regarding the efficacy of the solution that was
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`tested?
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`A.
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`Not in my opinion. There are -- there are a number of
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`weaknesses of this study that would cause a POSA to be quite
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`skeptical that even the 30-microgram-per-kilogram dosage would
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`Peck - Direct
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`Peck - Direct
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`39
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`Q.
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`We've heard that term "last patient out" a few times
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`during trial. What does that mean?
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`A.
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`That's the date that the very last patient has exited the
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`clinic or the study unit in a clinical trial.
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`Q.
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`Okay. Now, have you prepared a slide summarizing Study
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`2230 [sic]?
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`A.
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`Q.
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`I have.
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`Let's please turn to Plaintiffs' Demonstrative Exhibit
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`209. And let's just take this a piece at a time. Can you
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`summarize your opinion as to what the objective was of Study
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`2330?
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`THE COURT: Just again, this is Phase II?
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`MR. O'MALLEY: Phase II, correct.
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`THE COURT: Phase II. This is the Phase II study for
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`what became Aloxi®, right?
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`BY MR. O'MALLEY:
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`Q.
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`A.
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`Can you answer that question, Dr. Peck?
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`So, there were five Phase II studies. This is one of
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`them. It was an exploratory dose­ranging study in cancer
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`patients who were receiving chemotherapy-induced nausea and
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`vomiting -- who were experiencing that. It's an intravenous
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`study. And the purpose of this was to evaluate graded doses
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`to see the -- to evaluate the safety and to identify a
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`possible signal of benefit.
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`Q.
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`Now, what were the parameters of this study?
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`work. For example, there was an incomplete dose-response
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`pattern.
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`Q.
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`Okay. Before explaining that, why don't we get to the
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`table that you mentioned.
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`Let's look at Defendants' Trial Exhibit 227-0015. And
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`let's blow up the area around the table. Do you understand
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`what's set forth here?
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`A.
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`I do. Now, this comes from the final study report of
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`2330. And it is the primary results of the -- of the
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`potential for benefit. And what you see here are the doses
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`lined up from .3 up to 90 and one --
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`Q.
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`A.
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`Would you like a pointer? I'm sorry to interrupt.
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`Oh, I'm sorry. Right, right, right, okay.
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`So, what you see in this row here are the dose
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`assignments. As I say, there were about 25 subjects in each
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`group. There were a couple of different ways of evaluating
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`whether the drug was having an effect. One was called
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`complete control and the other was called complete response.
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`They differed very slightly, but each required that, you know,
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`there be no -- no vomiting and retching and no requirement for
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`rescue medicines.
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`And what you see here is that they -- they roughly line
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`up here, but to compare with the lowest dose groups, .3 to 1,
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`each of the others was statistically evaluated against that
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`group, and what you see --
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`Page 3 of 5
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`Peck - Cross
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`Peck - Redirect
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`result of the administration of the formulations that are at
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`issue in this case?
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`A.
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`Just saying that this table is not sufficient to inform
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`me about any one person in the clinical trial.
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`Q.
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`I didn't ask you about any one person.
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`I just asked you whether you can conclude that anybody
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`in the trial actually experienced a reduction in the
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`likelihood of CINV as a result of the administration of the
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`formulation in this case?
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`A.
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`The best you can say is that the raw data expressed as
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`percentage differ among these groups, but you really must
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`apply a statistical test, and in the case of a positive
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`control like this, you have to confirm that the positive --
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`that the active ingredient, this is -- I mean, the active drug
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`is actually working in this trial.
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`So there's a column missing, a very important column
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`missing, and that's the historical placebo. This is a
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`non-inferiority trial. And Dr. Fruehauf should have explained
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`that a non-inferiority trial is never validated until it's
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`compared with a historical control. And that's missing from
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`this.
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`Q.
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`A.
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`Q.
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`Did you finish your answer?
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`I did.
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`Okay. And so I'm just asking you, I think it's a "yes"
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`or "no" question, okay? And so let me just ask you: Can you
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`about a document entitled the FDA's Drug Review Process From
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`Information For Consumers Database?
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`A.
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`Yes, I do.
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`MR. O'MALLEY: I don't know if we're able to pull
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`that up. If I can ask the help of Mr. Lombardi's hot seat
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`guy. Thank you.
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`BY MR. O'MALLEY:
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`Q.
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`Now, this appears to be two pages of text, and there's
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`some, I don't know, cartoon figures in here. Have you seen
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`this before?
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`A.
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`Well, I think this was flashed up this morning or this
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`afternoon --
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`Q.
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`A.
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`Q.
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`A.
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`Before today?
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`I don't recall.
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`Is this an FDA Guidance?
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`No, it's not an FDA Guidance. It's a communication to
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`consumers to explain some aspects of drug development and
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`regulation.
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`MR. O'MALLEY: Could we turn to Page 2 of this
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`document, please.
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`BY MR. O'MALLEY:
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`Q.
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`And you were asked some questions about the bottom of
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`Page 2 regarding Phase II?
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`A.
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`Q.
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`Yes.
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`And in the middle of the paragraph, it states, "This
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`Peck - Redirect
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`175
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`tell from the data you're presented here whether anybody in
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`this study received a reduction in the likelihood of CINV as a
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`result of taking the formulations that are at issue in this
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`case?
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`A.
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`No.
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`MR. O'MALLEY: Objection, asked and answered.
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`MR. LOMBARDI: It's been -- it hasn't been answered.
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`THE COURT: He just answered.
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`THE WITNESS: I just answered "no."
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`MR. LOMBARDI: Thank you. Thank you.
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`Your Honor, if I could have a minute to confer.
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`THE COURT: Yes, always. Would you like to take a
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`little recess?
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`MR. LOMBARDI: I think that would be the easiest
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`thing to do.
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`THE COURT: That's fine.
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`MR. LOMBARDI: Thank you, Your Honor.
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`THE COURT: Okay.
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`(Recess taken.)
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`THE COURT: Mr. Lombardi?
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`MR. LOMBARDI: No further questions at this time,
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`your Honor.
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`THE COURT: Fine. Thank you. Redirect.
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`REDIRECT EXAMINATION BY MR. O'MALLEY:
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`Q.
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`Dr. Peck, do you recall you were asked some questions
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`Peck - Redirect
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`177
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`phase aims to obtain preliminary data on whether the drug
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`works in people who have a certain disease or condition."
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`Do you see that?
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`I do.
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`Is this discussion in this consumer piece consistent with
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`A.
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`Q.
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`your discussion of Phase II clinical trials during my
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`examination of you today?
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`A.
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`Well, I believe it is, given that we see the word
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`"preliminary" in there.
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`MR. O'MALLEY: Okay. Could we look at the conference
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`report opportunities for integration and so on with Dr. Peck
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`as first-named author. And, thank you, again, for the assist.
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`BY MR. O'MALLEY:
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`Q.
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`You were asked some questions on Page 609 of this
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`reference, and, in particular, towards the bottom on the
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`left-hand column regarding Phase II.
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`Do you recall that?
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`I do.
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`And, in particular, there's a statement here. I would
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`A.
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`Q.
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`like to direct you to towards about the third of the way down,
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`"The principal goal of Phase II studies is to provide
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`unequivocal evidence of the desired therapeutic effect."
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`Do you recall that?
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`I do.
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`And is this discussion in general that's set forth here
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`A.
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`Q.
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`consistent with your testimony regarding what Phase II
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`clinical trials are about?
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`A.
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`Yes, I think so. That's a goal. That's not always
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`achieved, but that's a goal.
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`MR. O'MALLEY: Now, if we can turn to DTX-1019, and
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`are you doing it or -- okay. 0009. Just wait till we switch
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`over the hot seat. Thanks again.
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`BY MR. O'MALLEY:
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`Q.
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`Now, I think you were asked some questions regarding the
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`first paragraph. "The data suggests that the four higher-dose
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`groups of palonosetron" and the dose groups were listed "were
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`in general clinically more effective than the lowest-dose
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`group," correct?
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`A.
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`Q.
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`Yes.
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`And before I get there, let me just, as the Court pointed
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`out, there's -- the next sentence reads, "A statistically
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`significant difference in the proportion of subjects with a
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`complete response was achieved only for the comparison between
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`.3-1 microgram per kilogram and 30-microgram-per-kilogram
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`doses (24 percent versus 50 percent, respectively; p equals
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`0.047)."
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`Do you see that?
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`I do.
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`That second sentence I read, is that consistent with your
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`A.
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`Q.
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`interpretation of the table from Study 2230 before the
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`interpretations in these type of FDA documents.
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`A.
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`Q.
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`A.
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`Q.
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`A.
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`I did.
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`Do I recall that correctly?
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`I did.
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`What did you mean by that?
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`Well, you know, this is a -- you know, when a company
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`says this clearly shows, clearly, you know, that's a judgment
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`call. It is a very positive qualification. It's sort of
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`meant to persuade, and it's -- what FDA in advertising calls
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`fluff. They permit a little fluff in advertising.
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`What they don't permit is submitting data that turns
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`out to be fraudulent or incomplete. That's a very serious
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`problem. But the way companies represent varies, and it
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`varies within the company over time, and we've certainly seen
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`this in this case.
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`Q.
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`Now, with respect to this same document and this
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`interpretation, you testified, I believe, that the FDA makes
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`up its own mind.
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`Do you recall that?
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`Well, certainly.
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`And what did the FDA decide with respect to Study 2230
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`A.
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`Q.
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`specifically whether it was sufficient to show efficacy of any
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`dose?
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`A.
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`Well, this isn't the document I think that documents
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`that, but in a 1999 meeting minutes with FDA, the FDA clearly
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`Peck - Redirect
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`179
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`181
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`reanalysis?
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`A.
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`Q.
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`Yes, it is.
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`Okay. Now, with respect to the first sentence, and
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`specifically the words, "clinically more effective," Mr.
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`Lombardi took you to several Helsinn or Syntex documents where
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`they characterized the Phase II data in terms of clearly -- in
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`terms of showing efficacy, the words varied.
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`Do you recall that?
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`I do.
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`And I believe you said that that was the author's
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`A.
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`Q.
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`interpretation.
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`Do you recall that?
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`MR. LOMBARDI: And, Your Honor, I object. There's no
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`foundation for this witness to testify as to what the author
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`was doing. I think he said that during the cross-examination.
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`THE COURT: Well, I'll permit latitude on the
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`redirect. Overruled as to this.
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`BY MR. O'MALLEY:
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`Q.
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`A.
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`Do you recall saying that?
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`I recall something like that, that representations by
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`companies before FDA and various settings vary with respect to
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`their championship and, you know, sort of attempt to persuade
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`FDA, but it's -- it's just a matter of words.
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`Q.
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`Now, you have said, I believe, that there was some
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`"wiggle room" with respect to characterizations or
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`Peck - Redirect
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`said that 2330, you know, would be admissible to the pivotal
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`study. The data could be supportive. It didn't say this
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`study report, it didn't say these results could be supportive,
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`but it referenced the data.
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`Q.
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`Now, if we could turn to DTX-0264.0009, and this is the
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`table that's attached to the August Consulting letter
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`requesting a meeting with the FDA.
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`Do you recall that?
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`I do. Yes, I do.
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`Now, you testified in cross-examination something about a
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`A.
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`Q.
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`historical control missing?
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`A.
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`Q.
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`A.
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`Yes.
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`Could you please explain what you meant by that.
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`I will. The term adequate and well controlled means
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`that -- and it's very well accepted in the scientific
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`community -- that in a randomized, blinded study, you compare
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`the main effect of interest with a control group.
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`When --
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`THE COURT: The main what of interest?
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`THE WITNESS: The main effect, so, for example, in
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`this case the reduction of nausea and vomiting and rescue
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`medicines.
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`It must be compared and it must be compared under
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`rigorous, statistical conditions. When the comparison group
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`is a placebo, there's very little question that you have a
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