168
`
`Civil Action
`
`No. 14-664-GMS
`Civil Action
`
`No. 14-666-GMS
`Civil Action
`
`)
`)
`
`))
`
`))
`
`)
`
`))
`
`))
`
`V.
`)
`WATSON LABORATORIES, INC.,
`ACTAVIS, INC., and ACTAVIS LLC, )
`)
`Defendants.
`)
`- - -
`ASTRAZENECA AB,
`)
`)
`Plaintiff,
`
`))
`
`))
`
`V.
`WOCKHARDT BIO AG and
`WOCKHARDT USA LLC,
`No. 14-667-GMS
`)
`Defendants.
`- - -
`Wilmington, Delaware
`Tuesday, September 20, 2016
`9:00 a.m.
`Day 2 of Bench Trial
`- - -
`BEFORE: HONORABLE GREGORY M. SLEET, U.S.D.C.J.
`CAPTION CONTINUES ON FOLLOWING PAGE
`
`)
`
`))
`
`))
`
`IN THE UNITED STATES DISTRICT COURT
`IN AND FOR THE DISTRICT OF DELAWARE
`- - -
`
`ASTRAZENECA AB,
`Plaintiff,
`
`V.
`AUROBINDO PHARMA LTD. AND
`AUROBINDO PHARMA U.S.A., INC.,
`Defendants.
`ASTRAZENECA AB,
`Plaintiff,
`
`)
`- - -
`)
`)
`
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`
`MYLAN - EXHIBIT 1028
`Mylan et al. v. AstraZeneca
`IPR2015-01340
`
`
`
`Civil Action
`
`No. 14-664-GMS
`Civil Action
`
`No. 14-666-GMS
`Civil Action
`
`)
`)
`
`))
`
`))
`
`)
`
`))
`
`))
`
`V.
`)
`WATSON LABORATORIES, INC.,
`ACTAVIS, INC., and ACTAVIS LLC, )
`)
`Defendants.
`)
`- - -
`ASTRAZENECA AB,
`)
`)
`Plaintiff,
`
`))
`
`))
`
`V.
`WOCKHARDT BIO AG and
`WOCKHARDT USA LLC,
`No. 14-667-GMS
`)
`Defendants.
`- - -
`Wilmington, Delaware
`Tuesday, September 20, 2016
`9:00 a.m.
`Day 2 of Bench Trial
`- - -
`BEFORE: HONORABLE GREGORY M. SLEET, U.S.D.C.J.
`CAPTION CONTINUES ON FOLLOWING PAGE
`
`)
`
`))
`
`))
`
`IN THE UNITED STATES DISTRICT COURT
`IN AND FOR THE DISTRICT OF DELAWARE
`- - -
`
`ASTRAZENECA AB,
`Plaintiff,
`
`V.
`AUROBINDO PHARMA LTD. AND
`AUROBINDO PHARMA U.S.A., INC.,
`Defendants.
`ASTRAZENECA AB,
`Plaintiff,
`
`)
`- - -
`)
`)
`
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`
`MYLAN - EXHIBIT 1028
`Mylan et al. v. AstraZeneca
`IPR2015-01340
`
`
`
`169
`
`Civil Action
`
`No. 14-694-GMS
`Civil Action
`
`No. 14-696-GMS
`
`Civil Action
`
`No. 14-697-GMS
`
`IN THE UNITED STATES DISTRICT COURT
`IN AND FOR THE DISTRICT OF DELAWARE
`- - -
`)
`)
`
`ASTRAZENECA AB,
`Plaintiff,
`
`))
`
`V.
`)
`SUN PHARMA GLOBAL FZE and SUN
`PHARMACEUTICAL INDUSTRIES LTD., )
`)
`Defendants.
`)
`- - -
`ASTRAZENECA AB,
`)
`)
`Plaintiff,
`
`))
`
`))
`
`))
`
`))
`
`V.
`MYLAN PHARMACEUTICALS, INC.,
`Defendant.
`
`)
`- - -
`)
`)
`
`))
`
`))
`
`))
`
`)
`- - -
`
`ASTRAZENECA AB,
`Plaintiff,
`
`V.
`AMNEAL PHARMACEUTICALS LLC,
`Defendant.
`
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`170
`
`APPEARANCES:
`MICHAEL P. KELLY, ESQ., and
`DANIEL M. SILVER, ESQ.
`McCarter & English, LLP
`-and-
`CHARLES E. LIPSEY, ESQ.,
`ROBERT F. SHAFFER, ESQ.,
`DAVID M. WEINGARTEN, Ph.D., ESQ., and
`NICOLE A CONLON, Ph.D., ESQ.
`Finnegan, Henderson, Farabow,
`Garrett & Dunner, L.L.P.
`(Washington, D.C.)
`
`Counsel for AstraZeneca AB
`KENNETH LAURENCE DORSNEY, ESQ.
`Morris James LLP
`-and-
`SAILESH K. PATEL, ESQ., and
`GEORGE YU, ESQ.
`Schiff Hardin LLP
`(New York, NY)
`
`Counsel for Aurobindo
`DOMINICK T. GATTUSO, ESQ.
`Proctor Heyman LLP
`-and-
`RALPH J. GABRIC, ESQ.,
`MARK H. REMUS, ESQ.,
`LAURA A. LYDIGSEN, ESQ., and
`JOSHUA JAMES, ESQ.
`Brinks Gilson & Lione
`(Chicago, IL)
`
`Counsel for Watson
`Laboratories and Actavis
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`
`
`171
`
`APPEARANCES CONTINUED:
`DAVID BILSON, ESQ.
`Phillips, Goldman, McLaughlin & Hall, P.A.
`-and-
`MAUREEN L. RURKA, ESQ., and
`CHRISTOPHER P. WILSON, ESQ.
`Winston & Strawn LLP
`(Chicago, IL)
`
`Counsel for Sun Pharma Global
`FZE and Sun Pharmaceutical
`and Amneal
`DAVID E. MOORE, ESQ.
`Potter Anderson & Corroon LLP
`-and-
`DOUGLAS H. CARSTEN, ESQ.,
`ELLIE F. STEINER, ESQ., and
`NELLIE AMJADA, ESQ.
`Wilson Sonsini Goodrich & Rosati
`(San Diego, CA)
`
`Counsel for Mylan
`- - -
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`
`
`349
`
`Lenhard - direct
`MR. SHAFFER: With that, your Honor.
`AstraZeneca calls as its next witness Dr. James Lenhard.
`... M. JAMES LENHARD, having been
`duly sworn as a witness, was examined and
`testified as follows ...
`THE COURT: Good afternoon, Doctor.
`THE WITNESS: Good afternoon.
`MR. SHAFFER: Your Honor, if I may approach?
`THE COURT: Yes.
`(Mr. Shaffer handed notebooks to the Court.)
`MR. SHAFFER: May I proceed, your Honor?
`THE COURT: Yes.
`DIRECT EXAMINATION
`
`BY MR. SHAFFER:
`Good afternoon, Dr. Lenhard.
`Q.
`Good afternoon.
`A.
`Could you please introduce yourself to the Court and
`Q.
`tell us your occupation?
`James Lenhard. I'm an endocrinologist practicing here
`A.
`in Wilmington, Delaware.
`So you're not a medicinal chemist?
`Q.
`Not yet.
`A.
`Doctor, you have been retained on behalf of
`Q.
`AstraZeneca. What are you here to testify about today?
`I was asked to give my opinion about a drug,
`A.
`
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`
`
`Lenhard - direct
`
`393
`
`MR. Shaffer: Thank you, Doctor. I pass the
`
`witness.
`
`THE COURT: Cross-examine.
`MS. STEINER: May I approach, Your Honor?
`THE COURT: Yes, you may.
`You may proceed.
`MS. STEINER: Thank you, Your Honor.
`CROSS-EXAMINATION
`Good afternoon, Doctor?
`
`Q.
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`
`
`Lenhard - cross
`
`394
`
`Good afternoon.
`A.
`My name is Ellie Steiner, and I will be asking you a
`Q.
`few questions on behalf of the defendants.
`Very good.
`A.
`We just heard about your background and experience
`Q.
`treating diabetes. Correct?
`Yes.
`A.
`Many of the patients you have seen have diabetes.
`Q.
`Correct? I believe you said 60 percent or so?
`60 to 70 percent, that's correct.
`A.
`For purposes of your opinion today, the relevant date
`Q.
`that you considered is February 16th, 2001. Correct?
`I believe it was the year 2000 that the drug was
`A.
`discovered.
`So were your opinions based on the year 2000?
`Q.
`Late 2000, yes.
`A.
`So you were deposed in this case. Correct?
`Q.
`I was.
`A.
`Did you provide correct and accurate testimony in that
`Q.
`deposition?
`I attempted to do so.
`A.
`If you could turn in your folder to the tab titled
`Q.
`deposition. And go to Page 25. Starting at Line 16. Let
`me know if I am reading this correctly?
`THE COURT: Why don't you tell him the lines
`
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`
`
`395
`
`Lenhard - cross
`that you want him to review and let him review them
`yourself.
`
`MS. STEINER: Sure.
`BY MS. STEINER:
`If you could review Lines 16 to 18 on Page 25?
`Q.
`Okay.
`A.
`
`THE COURT: Now you can question him.
`BY MS. STEINER:
`So does that refresh your recollection that the date,
`Q.
`relevant date for the purposes of your opinion is February
`16, 2001?
`Whether it was late 2000 or February 2001, I am not
`A.
`sure is really relevant. There were no clinical events that
`occurred in those few months in between the two.
`So, for purposes of today's discussion let's go with
`Q.
`2001. In 2001 there were five classes of oral medications
`available to treat Type 2 diabetes. Correct, Doctor?
`Yes.
`A.
`Are these drugs still available today?
`Q.
`Yes, they are.
`A.
`In 2001, the first line of therapy for Type 2 diabetes
`Q.
`was Metformin. Correct?
`That's correct.
`A.
`I believe you testified earlier that Metformin remains
`Q.
`the first line of therapy for Type 2 diabetes today.
`
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`
`
`Lenhard - cross
`
`396
`
`Correct?
`That's correct.
`A.
`Is there an oral medication for treatment of Type 2
`Q.
`diabetes that is prescribed more frequently than Metformin?
`No.
`A.
`There is no clear second choice of drug that you most
`Q.
`frequently prescribe. Correct?
`Correct.
`A.
`So would you agree that back in February 2001 there
`Q.
`was a need for new treatment options for Type 2 diabetes?
`Yes, I would.
`A.
`Is it correct that there is still a need for new
`Q.
`treatment options for Type 2 diabetes today?
`We still don't have a cure. So, yes, there is a need.
`A.
`So, Doctor, as of February 16, 2001, there was no
`Q.
`failure of DPP-4 inhibitors. Correct?
`Correct.
`A.
`You testified earlier that as of February 2001
`Q.
`Vildagliptin had been discovered. Correct?
`It had been, yes.
`A.
`You testified earlier that you are aware that
`Q.
`Vildagliptin is currently available in the E.U. for
`treatment of Type 2 diabetes. Correct?
`I am aware, yes.
`A.
`So a patient could go to any country in the E.U. and
`Q.
`
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`
`
`397
`
`Lenhard - cross
`get a prescription for Vildagliptin. Correct?
`I am not an expert on European drugs, but that sounds
`A.
`like a reasonable possibility.
`When a drug is approved here in the United States, it
`Q.
`is presumed to be safe and effective. Yes?
`Yes.
`A.
`Do you have any reason to assume that a drug approved
`Q.
`in the E.U. is not safe and effective?
`I am not up-to-date in the difference of the approval
`A.
`requirements for the E.U. versus the approval requirements
`for the FDA.
`Sitting here today do you have any reason to believe
`Q.
`that a drug that is approved by the regulatory agency in the
`E.U. would not be safe and effective?
`I think there are shades of gray. If the drug were
`A.
`poison and were not safe in any dose or effective in any
`dose, it would not be approved in either location.
`Now, in addition to saxagliptin, you testified earlier
`Q.
`that there are three other FDA-approved DPP-4s. Correct?
`Yes.
`A.
`Those are sitagliptin, linagliptin and alogliptin?
`Q.
`Correct.
`A.
`Sitagliptin was the first DPP-4 inhibitor that
`Q.
`received FDA approval in the United States. Correct?
`It is.
`A.
`
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`
`
`398
`
`Lenhard - cross
`You testified earlier that saxagliptin can be a
`Q.
`first-line therapy?
`Correct.
`A.
`Is that specifically saxagliptin, or did you mean
`Q.
`class of DPP-4s?
`I don't recall my exact wording. But what I should
`A.
`have said is that a DPP-4 inhibitor such as saxagliptin
`could potentially be used as initial monotherapy.
`So your testimony wasn't specific to saxagliptin, it
`Q.
`could have included any of the four DPP4s in that class?
`That's correct.
`A.
`Now, Doctor, you also testified earlier that
`Q.
`saxagliptin demonstrated unexpected results because of its
`favorable side effect profile of once-daily dosing and
`efficacy. Correct?
`That's correct.
`A.
`That would apply to the other members of the DPP-4
`Q.
`class that have been FDA-approved. Correct?
`That would.
`A.
`So each of the four that are in the DPP-4 class?
`Q.
`Yes.
`A.
`You do not prescribe saxagliptin more frequently than
`Q.
`any of the other DPP-4 inhibitors on the market. Correct?
`Not to my knowledge. I never did an actual
`A.
`tabulation, but I don't believe so.
`
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`
`
`399
`
`Lenhard - cross
`Is there one that you do prescribe more often than the
`Q.
`others?
`Not that I am aware.
`A.
`It's your opinion that there is no meaningful
`Q.
`difference in the side effect profile of the DPP-4
`inhibitors on the market. Is that correct?
`Correct.
`A.
`Now, are you aware, Doctor, that in April 2016 FDA
`Q.
`required that a warning be added to the saxagliptin label?
`Yes.
`A.
`Do you know what the content of that warning was?
`Q.
`There were at least three warnings from the FDA. I
`A.
`think you are referring to on that particular date pertained
`to hospitalization for congestive heart failure.
`If you could turn in your binder to JTX-146?
`Q.
`Okay.
`A.
`So this was an FDA warning that issued in April 2016.
`Q.
`Is that correct?
`Yes, it is.
`A.
`You see in the first paragraph just after the date it
`Q.
`says, A U.S. food and drug Administration (FDA) safety
`review has found that type 2 diabetes medicines containing
`saxagliptin and alogliptin may increase the risk of heart
`disease, particularly in patients who already have heart or
`kidney disease."
`
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`
`
`Lenhard - cross
`
`400
`
`I see that.
`A.
`You are familiar with this warning, is this the
`Q.
`warning that you had in mind?
`It is.
`A.
`And sitagliptin does not have a similar warning.
`Q.
`Correct?
`It does not.
`A.
`And neither does linagliptin?
`Q.
`It does not.
`A.
`You mentioned earlier that certain Type 2 diabetes
`Q.
`medications can have liver effects, lead to liver toxicity,
`for example, I think you were discussing vildagliptin. And
`you mentioned you only have one liver. So that is an
`important warning and precaution. You only have one heart.
`Correct?
`Also correct.
`A.
`So it is the FDA warning be that issued in April of
`Q.
`2016, is that significant?
`I think any time the FDA tells us that we need to
`A.
`watch for a side effect from a medication, we need to pay
`attention to that. But I did not consider their warning to
`be clinically relevant.
`Why is that?
`Q.
`There are four particular reasons. First, the
`A.
`relative risk in that study. It was a study that was not
`
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`
`
`Lenhard - cross
`significant, that was the briefings from the study, showed
`that compared to placebo, the risk of hospitalization for
`congestive heart failure increased from the 2.5 to 3.2
`percent.
`
`401
`
`Second, there was no increase in congestive
`heart failure. There was an increase in hospitalization for
`heart failure. How can you have an increase in
`hospitalization for heart failure without having an increase
`in actual congestive heart failure?
`I didn't consider that to be consistent.
`Third, the statistically significant increase in
`congestive heart failure only occurred in the first year.
`Afterwards, it was not sustained. That doesn't mean it's
`impossible that's a drug effect, but it is not typical for
`what a drug would usually do.
`There was no accumulation of risk. It was only
`the first year.
`Fourth, these were data obtained from secondary
`end points and not the primary end point. And I think we
`should be very cautions in making strong conclusions from
`secondary end points.
`And FDA considered the results significant enough to
`Q.
`issue this warning and required that the label include that
`warning; is that correct?
`As well they should. We need to know about
`A.
`
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`
`
`402
`
`Lenhard - cross
`possibilities of events.
`Now, Doctor, do you view DPP-4 inhibitors as
`Q.
`interchangeable?
`Relatively.
`A.
`So if a patient were on one DPP-4 inhibitor and you
`Q.
`wanted to switch them to another, what would be the reason?
`Side effects?
`Correct. If a patient had a severe side effect for
`A.
`one DPP-4 inhibitor and they were taken off it and they
`asked to go back on it, I would not put them back on it
`again. I might use a different drug in a class.
`But generally side effect profile, as you testified
`Q.
`earlier, are the same for the class; is that correct?
`Correct.
`A.
`Now, you agree that FDA-approved drugs to treat Type 2
`Q.
`diabetes were considered by FDA to have a favorable side
`effect profile; is that correct?
`Are you referring to every drug approved by the FDA?
`A.
`To treat Type 2 diabetes?
`Q.
`They have a favorable enough side effect profile to
`A.
`warrant FDA approval.
`And do you agree that with the exception of the one
`Q.
`drug, FDA-approved drugs to treat Type 2 diabetes are
`clinically effective?
`I'm sorry. You could rephrase that?
`A.
`
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`
`403
`
`Lenhard - cross
`Sure. Let me start this way. Do you believe that
`Q.
`FDA-approved drugs, FDA-approved drugs to treat Type 2
`diabetes are clinically effective?
`Yes.
`A.
`All of them?
`Q.
`To varying degrees, yes.
`A.
`MS. STEINER: I have no further questions.
`THE COURT: Thank you, counsel. Any redirect?
`MR. SHAFFER: Your Honor, no redirect.
`THE COURT: Dr. Lenhard, thank you.
`THE WITNESS: Thank you.
`(Witness excused.)
`
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