Case 1:14-cv-11689-RWZ Document 92 Filed 02/17/15 Page 1 of 8

UNITED STATES DISTRICT COURT

DISTRICT OF MASSACHUSETTS

ZOGENIX, INC.,
Plaintiff,
v.
CHARLES D. BAKER, in his official capacity as
the GOVERNOR OF MASSACHUSETTS,1
MONICA BHAREL, MD, MPH, in her official
capacity as DEPARTMENT OF PUBLIC HEALTH
COMMISSIONER,
CANDACE LAPIDUS SLOANE, M.D., et al., in
their official capacities as members of the
MASSACHUSETTS BOARD OF
REGISTRATION IN MEDICINE,

CIVIL ACTION
No. 1:14-cv-11689-RWZ

KAREN M. RYLE, MS, R.PH, et al., in their

official capacities as members of the
MASSACHUSETTS BOARD OF
REGISTRATION IN PHARMACY, and
DIPU PATEL-JUNANKAR, PA-C, et al., in their
official capacities as members of the
MASSACHUSETTS BOARD OF
REGISTRATION OF PHYSICIAN ASSISTANTS,
Defendants.
OPPOSITION TO PLAINTIFFS MOTION FOR LEAVE TO FILE
SECOND SUPPLEMENTAL BRIEF
For the second time the plaintiff, Zogenix, Inc., seeks leave to file a supplemental brief in
connection with Defendants pending motion to dismiss Zogenixs third amended complaint.
Zogenix incorrectly characterizes its proffered brief as a submission that simply informs the
Court of a change to the regulatory landscape. Defendants certainly do not object to informing
1

Certain of the original named defendants, sued in their official capacities, no longer hold those
offices. The new officeholders have been substituted.
1

Case 1:14-cv-11689-RWZ Document 92 Filed 02/17/15 Page 2 of 8

the Court that the FDA has recently approved Zogenixs sNDA relating to a new formulation of
Zohydro ER. In fact, Defendants offered to do so through a joint filing.2 Defendants do object,
however, to Zogenixs inaccurate descriptions of the sNDA approval, communications between
counsel for the parties regarding same, and FDAs prior approval of Purdues drug Hysingla.
Defendants further object to Zogenixs unauthorized and inappropriate attempts to reargue its
opposition to the pending motion to dismiss based on its inaccurate accounts of these
developments.
In the event the Court allows Zogenix to file its proffered second supplemental brief,
Defendants respectfully request that the Court treat this opposition as their response thereto.
FDAs recent approvals change nothing as regards Defendants pending motion to dismiss, and
the motion should be allowed for the reasons previously briefed.
1. Zogenix does not accurately describe the facts with respect to the sNDA
approval.
As we have previously noted, the FDA has four tiers of claims regarding abusedeterrence that it may approve for inclusion on the labels of FDA-approved opioids. See FDAs
Draft Guidance for Industry, Abuse-Deterrent Opioids Evaluation and Labeling, available at
http://goo.gl/mJLwAj, (Draft Guidance) at 18-20. Tier 1 approval allows Claims that a
Product is Formulated with Physicochemical Barriers to Abuse; Tier 2 approval allows Claims
that a Product is Expected to Reduce or Block the Effect of the Opioid When the Product is
Manipulated; Tier 3 approval allows Claims that a Product is Expected to Result in a
Meaningful Reduction in Abuse; and Tier 4 approval allows Claims that a Product has
2

Zogenix has attached to its proffered supplemental brief only the first of a series of pre-filing
email exchanges between counsel, omitting portions of the exchange that contain this offer and
directly contradict assertions contained in Zogenixs proposed filing. Additional email
exchanges (in reverse chronological order) are attached hereto as Exhibit 1.
2

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Demonstrated Reduced Abuse in the Community. Id. at 19-20. Because the FDA approves
drugs only for use as recommended in the . . . agreed-upon labeling text, see, e.g., Second
Supplemental Memorandum of Plaintiff Zogenix, Inc. Regarding Regulatory Landscape (Supp.
Mem.), Exh. 1 at 1, unless and until the FDA approves labeling claim(s) related to abusedeterrence an opioid is, for purposes of FDAs approval process, non-abuse-deterrent.
And that is the situation with the reformulated version of Zohydro that is the subject of
the sNDA recently approved by the FDA. The FDA did not approve any labeling claim
whatsoever relating to abuse-deterrence. See FDA Timeline of Selected FDA Activities &
Significant Events Addressing Opioid Misuse & Abuse, available at http://goo.gl/x1t5Yy, at 11
(On January 30, [2015,] FDA approved a modified formulation of Zohydro ER . . . . The FDA
has not approved an abuse-deterrent labeling claim for Zohydro ER.); Supp. Mem., Exh. 1.3
Thus, this is not just a matter of future data submissions perhaps leading to more explicit abusedeterrent claims on the Zohydro label than are currently approved, see Supp. Mem. at 1; no
abuse-deterrence claims are currently permitted. Because the FDA approval therefore treats the
reformulated Zohydro as non-abuse-deterrent, and Defendants regulations apply to any nonabuse-deterrent version of Zohydro, the Defendants have acted entirely consistently with the
FDA approval in confirming that their regulations apply to the reformulated Zohydro. There is

Obviously, the mere reflection on the new Zohydro label of the presence of the ingredient
polyethylene oxide, noted by Zogenix at page 1 of its proffered supplemental memorandum,
does not constitute or permit a claim related to abuse-deterrence, whether or not the FDA has
determined that the same ingredient acts in other opioids in such a manner as to permit claims of
abuse-deterrence. And the approved language in the Abuse section of the Zohydro label
containing warnings about intravenous abuse, cited in the supplemental memorandum at 1, has
nothing to do with abuse-deterrence and certainly does not permit any claims relative thereto.
See Supp. Mem., Exh. 3, 9.2 (With intravenous abuse, the inactive ingredients in ZOHYDRO
ER can result in death, local tissue necrosis, infection, pulmonary granulomas, and increased risk
of endocarditis and valvular heart injury. Parenteral drug abuse is commonly associated with
transmission of infectious diseases such as hepatitis and HIV.).
3

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simply no basis for any distinction between the two versions of Zohydro based on the FDA
approvals to date.
2. Zogenix does not accurately describe the facts with respect to counsel
communications.
Defendants do not have access to any of Zogenixs submissions relative to the sNDA
approval and do not know, for instance, whether Zogenix even sought approval of a labeling
claim relative to abuse-deterrence. If it did so, then the FDA must have affirmatively found a
labeling claim of abuse-deterrence to be inappropriate, rejecting (assuming the request covered
such a claim) even a Tier 1 claim that the reformulated Zohydro is Formulated with
Physicochemical Barriers to Abuse. Draft Guidance at 19. In any event, because Defendants
have no access to information regarding the FDA approval process or Zogenixs submissions,
when Zogenixs counsel raised an issue as to the import of the FDAs sNDA approval under
Defendants regulations, Defendants counsel inquired whether Zogenix wished to supply
Defendants with any information.4 Defendants counsel did not ask[ ] for detailed information
about the drug and its approval process, Supp. Mem. at 2, in the sense of suggesting that
Zogenix was bound to supply that information, but rather invited Zogenix to supply such
information as it desired to bring to Defendants attention in support of the suggestion that the
Defendants regulations might not apply to the reformulated Zohydro. See Supp. Mem., Exh. 6.
Subsequent communications made clear that Zogenix had no intention of providing any
supportive information to Defendants and, as Defendants counsel explained in a February 9
email to Zogenixs counsel, [s]ince [Zogenix] therefore relies exclusively on the mere fact of
the FDA sNDA approval, and since that sNDA approval entails no determination that the new
4

At the time Defendants counsel so inquired, the FDAs approval letter was not even available
on the FDA website.
4

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version is any more abuse-deterrent than the original version, the state regulations obviously
apply to the new version of Zohydro. See Exhibit 1 hereto.
As counsels email of February 4 reflects, see id., Defendants were especially interested
in learning from Zogenix whether the question of abuse-deterrence was even before the FDA
and, if it was, whether the FDA affirmatively rejected Zogenixs assertion that its new
formulation is potentially abuse-deterrent. If the question of abuse-deterrence was not before the
FDA, Defendants wondered whether Zogenix had information that could potentially support a
labeling claim of abuse-deterrence under the FDA Draft Guidance. But whatever Zogenixs
responses may have been, Defendants standard for reviewing any such information was not
unspecified, as Zogenix suggests. Supp. Mem. at 2. Defendants previously informed the Court
and Zogenix that if the FDAs Draft Guidance permits an opioid otherwise subject to
Defendants regulations to be labeled as expected to deter abuse, Defendants regulations do not
apply to that drug. See Opposition to Plaintiffs Motion for Leave to File Supplemental Brief at
4; Transcript, 12/3/14 Hearing at 34 (statement by Defendants counsel explaining that the FDA
has recognized that [Hysingla] has asserted abuse-deterrent properties, that [Purdue] has some
clinical trials to back that up and that, while the FDA has not made a final conclusion that the
drugs formulation in fact deters abuse, the hurdle that Purdue has surpassed is still a very high
threshold, and if [Zogenix] can establish that they meet that same threshold, our view is our
regulations dont apply to the new version of Zohydro). It was simply unclear here (and still is)
whether the FDA was called upon to make any actual determination regarding abuse-deterrence
and how the Draft Guidance would apply to any information Zogenix has developed regarding
the asserted abuse-deterrent potential of its reformulated drug.

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3. Zogenix does not accurately describe the facts regarding Hysingla.

Contrary to Zogenixs assertions, there is no inconsistency between Defendants position
vis--vis the reformulated Zohydro and their previous conclusion that their regulations do not
apply to Purdues drug Hysingla. The FDA has approved labeling for Hysingla describing the
products abuse-deterrent properties consistent with the FDAs Draft Guidance. See FDA News
Release, available at http://goo.gl/AWYG2p. Specifically, [t]he FDA has determined that the
physical and chemical properties of Hysingla ER are expected to make abuse by [specified]
routes difficult. Id. Thus, Purdue is not only eligible under the Draft Guidance for, but has
actually received, the FDAs approval to market Hysinglas formulation as expected to deter
abuse. Id. Hysingla, unlike both the new and original forms of Zohydro, is therefore in abuse
deterrent form for purposes of, and accordingly not subject to, Defendants regulations.
Zogenix argues that the use of the phrase abuse deterrent form in Defendants
regulations somehow mandates application of those regulations to Hysingla, even though the
FDA has approved that drug to be marketed with abuse-deterrence claims, because the approved
claims indicate that Hysingla has certain properties that are expected to deter abuse, rather
than that the drug actually does deter abuse. Supp. Mem. at 2 (emphasis in original). With
this argument Zogenix, contrary to its claims and other arguments in this case, seems to insist
that Defendants deviate from the FDAs guidance setting four permissible levels of claimed
abuse-deterrence and apply the state regulations to any otherwise covered opioid unless it
qualifies for the highest tier (Tier 4) claims under FDAs guidance namely, Claims that a
Product has Demonstrated Reduced Abuse in the Community. Draft Guidance at 20. No such
obligation can be read into the mere use in Defendants regulations of the phrasing abuse
deterrent form rather than abuse deterrent properties or properties that are expected to deter

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abuse. Nor does Zogenix correctly portray Defendants position when it describes that position
as a suggestion that some statute exempts drugs that contain ingredients designed to deter
abuse. Supp. Mem. at 3. It is unclear what statute Zogenix is referring to; if it means to refer
instead to Defendants regulations, those regulations cannot reasonably be read as exempting an
opioid just because it contains an ingredient that a manufacturer asserts is designed to deter
abuse. And again, adoption of that interpretation would run counter to the FDA standards on
abuse-deterrence.
4. Zogenix misunderstands the implications of these facts for Defendants pending
motion.
Since Defendants are following the FDAs lead in their treatment of both Zohydro, as
reformulated, and Hysingla, nothing about these facts reflects an inconsistency with federal law
or independent, arbitrary line-drawing, see Supp. Mem. at 2-3, that could possibly help
Zogenixs preemption claim. Defendants are not engaged in any separate drug approval
process, applying their own standards or supplanting FDA judgments on the question of abusedeterrence, or interpret[ing] FDA labeling decisions. See id. at 3. Defendants are instead
applying FDAs standards and clear FDA labeling decisions in the context of state regulations
governing the actions of medical and pharmacy professionals.
Moreover, the only regulation of the Defendants still before the Court with respect to
Zogenixs preemption claim is the pharmacy boards regulation limiting the personnel who may
handle Zohydro within pharmacies. Zogenix does not so much as attempt to demonstrate any
relevance of the FDAs sNDA approval of the reformulated version of Zohydro to that sole
outstanding preemption claim, and there is none. As in its other briefs, Zogenix offers no reason
to conclude that the pharmacy boards limited restriction on the handling of Zohydro within

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pharmacies will have any effect whatsoever on the ability of Massachusetts patients to fill
prescriptions for Zohydro, whether in its original form or as reformulated. In the absence of any
plausible allegation that Defendants regulations will substantially impede patients ability to fill
Zohydro prescriptions, Zogenix has no preemption claim.
****************************************************************
For these reasons, Zogenixs motion to file yet another supplemental memorandum
should be denied. To the extent the motion is allowed, Defendants respectfully request that the
Court accept this filing as their response. Zogenixs latest memorandum changes nothing, and its
third amended complaint should be dismissed in its entirety.
Respectfully submitted,
DEFENDANTS
By their counsel,

/s/ Jo Ann Shotwell Kaplan

Jo Ann Shotwell Kaplan (BBO #459800)
Eric Gold (BBO #660393)
Anne McLaughlin (BBO #666081)
Julia Kobick (BBO #680194)
Assistant Attorneys General
One Ashburton Place, 20th Floor
Boston, MA 02108

Dated: February 17, 2015

Certificate of Service
The undersigned counsel hereby certifies, this 17th day of February 2015, that this
document was filed through the Electronic Case Filing (ECF) system and thus copies will be sent
electronically to the registered participants as identified on the Notice of Electronic Filing
(NEF); paper copies will be sent to any non-registered parties so indicated on the NEF.
/s/ Jo Ann Shotwell Kaplan
Jo Ann Shotwell Kaplan