After a Draw in Court, Zogenix and Massachusetts Battle Over ZOHYDRO ER May Have to Proceed to a Penalty Shootout Round

By Kurt R. Karst –      

We watched the World Cup final between Germany and Argentina this past weekend and were pleased with the outcome (well, at least this blogger was).  Things got pretty intense as the minutes in extra time ticked away, edging the match ever closer to a possible penalty shootout round to determine the winner.  Thankfully, Germany’s (Super) Mario Götze scored a goal in the 113th minute, giving Germany a fourth World Cup.  Zogenix, Inc. (“Zogenix”), the sponsor of ZOHYDRO ER (hydrocodone bitartrate) Extended-release Capsules, which FDA approved on October 25, 2013 under NDA No. 202880 for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate, was not so lucky in its latest match against Massachusetts Governor Deval Patrick.  Last week, the U.S. District Court for the District of Massachusetts issued a decision allowing in part and denying in part the company’s Motion for a Preliminary Injunction, while denying the Commonwealth’s Motion to Dismiss (opposition briefs are available here and here).  Zogenix had hoped to score a total victory against the Commonwealth, but the court’s ruling means that we are likely far off from naming a winner in this match.

As we previously reported (here and here), Zogenix first sued Massachusetts Governor Deval Patrick and other Commonwealth officials after the Massachusetts Department of Public Health (“DPH”) and its Commissioner, Cheryl Bartlett, RN, took actions to combat opioid overdose, including granting DPH “emergency powers” to, among other things, ban the prescribing and dispensing of ZOHYDRO ER.  Zogenix filed a Complaint and a Motion for Temporary Restraining Order and Preliminary Injunction alleging that the Commonwealth’s ban on ZOHYDRO ER is unconstitutional because the ban violates the Supremacy Clause, the dormant Commerce Clause, and the federal Contracts Clause of the U.S. Constitution.  Shortly thereafter, the district court found that Governor Patrick’s March 27, 2014 Declaration of Emergency and the March 27th order of the Commissioner of the Department of Public Health banning the sale and distribution of ZOHYDRO ER obstructed FDA’s Congressionally-given charge.  The court allowed Zogenix’s motion for preliminary injunctive relief and enjoined, until April 22, 2014, the Commonwealth from taking any action to implement or enforce the declaration and order.

Though down, the Commonwealth was not out.  Commonwealth officials went right to work after the district court’s decision to come up with emergency regulations that might pass muster under a preemption analysis.  The result was the announcement of an April 22, 2014 emergency order from DPH Commissioner Bartlett and an emergency regulation promulgated by the Board of Registration in Medicine (“BORIM”) requiring an individually licensed prescriber to do the following before prescribing “a hydrocodone-only extended release medication that is not in an abuse deterrent form” (i.e., ZOHYDRO ER):

(a) Thoroughly assess the patient, including an evaluation of the patient’s risk factors, substance abuse history, presenting conditions(s), current medication(s), and a check of the online Prescription Monitoring Program;

(b) Discuss the risks and benefits of the medication with the patient;

(c) Enter into a Pain Management Treatment Agreement with the patient that shall appropriately address drug screening, pill counts, safe storage and disposal and other requirements based on the patient’s diagnoses, treatment plan, and risk assessment;

(d) Supply a Letter of Medical Necessity as required by the Board of Registration in Pharmacy that includes the patient’s diagnoses and treatment plan, verifies that other pain management treatments have failed, indicates that a risk assessment was performed and that the licensee and the patient have entered into a Pain Management Treatment Agreement; and

(e) Document 243 CMR 2.07(25)(a)-(d) in the patient’s medical record.

Other ZOHYDRO ER regulations followed in the coming weeks.  First, On May 6, 2014, the Board of Registration in Pharmacy (“BORIP”) promulgated two regulations (here and here) saying that “[a] certified pharmacy technician, pharmacy technician, pharmacy technician trainee, or pharmacy intern may not handle [ZOHYDRO ER],” and that before dispensing ZOHYDRO ER a pharmacist must satisfy a bevy of prerequisites,  including: (1) storing Zohydro in a locked cabinet; (2) dispensing Zohydro in a container with a child-proof safety cap; (3) reviewing the Letter of Medical Necessity; (4) including a warning about Zohydro’s dangers; (5) providing counseling on various issues; and (6) checking the patient’s history on the Prescription Monitoring Program.  Second, on May 8, 2014, the Board of Registration of Physicians Assistants (“BOROPA”) promulgated a set of regulations identical to the ones BORIM passed two days before.  These and the previous April 2014 regulations are referred to generally in court papers as the “Letter of Medical Necessity (‘LMN’) regulation” and the “pharmacist-only regulation.”

Zogenix filed a Motion for Preliminary Injunction on May 23, 2014 arguing that the new slate of regulations have the cumulative effect of creating an implicit ban on ZOHYDRO ER (i.e., obstacle preemption) and therefore “suffer[] from the same preemption problem as the first ban the Court already enjoined.”  Zogenix also alleged that the regulations violate the Contract Clause and the Commerce Clause of the U.S. Constitution, as well as the Equal Protection Clause “by singling out Zohydro™ ER for draconian restrictions not applicable to any other extended-release opioid products.”  (Nearly a doppelgängerof the counts Zogenix lodged in the company’s initial court papers filed in April.)

The Commonwealth shot back with a Motion to Dismiss. 

The Boards’ emergency regulations are not preempted by the [FDC Act] because, as the FDA itself has repeatedly acknowledged, States retain their traditional authority to regulate the medical and pharmacy professions, including the prescribing and dispensing of medications.  Nor do these emergency regulations begin to constitute an “effective ban” on Zohydro.  As the FDA Commissioner has indicated, they are instead reasonable requirements consistent with both best medical practices and longstanding parallel federal and state responsibilities in the field of drug regulation.  And Zogenix’s class-of-one equal protection claim is equally unavailing, because (1) the claim is not available in the circumstances present here, (2) critical elements of the claim are not (and cannot be) alleged, and (3) clear rational basis exists for the Board’s emergency regulations.

The Commonwealth also argued that Zogenix lacked standing to bring the suit and that the case should be dismissed for lack of subject matter jurisdiction.

In her July 8th decision, Judge Rya W. Zobel zeroed in on the essence of the case: obstacle preemption.  (Judge Zobel gave short schrift – the German spelling – to Zogenix’s Equal Protection Clause argument, saying “[t]hat argument is misplaced.”  Similarly, Judge Zobel did not consider Zogenix’s Contract Clause and the Commerce Clause arguments, saying that they were “undeveloped.”)  But to make such a preemption analysis, Judge Zobel she must do what the U.S. Supreme Court instructed in Savage v. Jones, 225 U.S. 501 (1912): “assess whether the regulations prevent the accomplishment of the FDCA’s objective that safe and effective drugs be available to the public.”  Her assessment: the LMN regulation is ambiguous and unclear, and the pharmacist-only regulation is uncertain. 

By any reckoning, the text of the “LMN regulation” is ambiguous.  Exactly what “pain management treatments” must fail before a doctor may prescribe Zohydro?  Plaintiff believes other opioids must fail.  Defendants do not believe a physician must prescribe other opioids before she may prescribe Zohydro. . . .  [I]f the Commonwealth interprets its regulation to make Zohydro a last-resort opioid, it undeniably makes Zohydro less available.  That presents a constitutional problem.

The “LMN regulation” is unclear in another way.  How long ago must the “other pain management treatments” have failed? . . .  If the Commonwealth interpreted its regulation to require a fresh failure as a precondition to each 30-day Zohydro prescription, it would severely frustrate Zohydro’s availability and pose significant constitutional concerns.

As for the “pharmacist-only regulation,” the parties rely on competing affidavits.  In a sealed declaration, Zogenix co-founder and Chief Executive Officer Roger L. Hawley discloses that unspecified major retail pharmacy chains do not plan to stock Zohydro because the “pharmacist-only regulation” is “fundamentally incompatible with personnel infrastructure and established policies for dispensing ER/LA opioids.”  Defendants present the affidavit of Michael Reppucci, R. Ph., owner of and pharmacist at Inman Pharmacy in Cambridge, Massachusetts.  Reppucci states that because BORIP already regulates pharmacy technicians, “prohibiting any pharmacy technicians from transporting and handling Zohydro does not add any substantial administrative burden or present substantial logistical problems.”  Neither party directs the court to any pharmacy’s announcement that it will or will not carry Zohydro.

Given the uncertainty as to how the Commonwealth might interpret and enforce the regulations, and a lack of an enforcement record on which to assess whether there is a case for obstacle preemption, Judge Zobel allowed Zogenix’s motion to preliminarily enjoin the LMN regulation, but with the caveat that “[i]f defendants provide adequate and constitutional guidance to physicians regarding the prerequisites for prescribing Zohydro in compliance with the regulation, then they may thereafter move to lift the injunction.”  On the other hand, with respect to the pharmacist-only regulation, Judge Zobel concluded that “[b]ecause its sealed declaration does not provide sufficient detail that pharmacies will not carry Zohydro, plaintiff has not met its burden of proof on the “pharmacist-only regulation,” and that Zogenix’s Motion for a Preliminary Injunction “is denied without prejudice to renewal upon a more detailed submission.”

So it’s not quite “goodbye” to this controversy, but rather – and quite literally – “auf Wiedersehen” (until we meet again).