Its Getting Bulkier Every Day for This Section 503B Facility: Athenex Announces a Product Launch, Moves to Intervene in the Endo/Par Bulks Lawsuit Against FDA, and Files a Declaratory Judgment Complaint

August 15, 2018By Karla L. Palmer

On August 13, 2018, Buffalo, New York-based Athenex Pharma Solutions, LLC and Athenex Pharmaceutical Division, LLC (Athenex) announced the launch of their vasopressin compounded formulation injection ready-to-use product line (see Press Release here). It also moved to intervene (either as of right or permissively) in a pending lawsuit filed in October 2017 by Par Sterile Products and Endo Par Innovation Company (Endo/Par) (blogged about here). In yet a third punch, Athenex also filed a declaratory judgment action against Endo/Par in the United States District Court for the Western District of New York alleging non-infringement and invalidity claims for several of the defendant’s Vasostrict® patents.

The 2017 Endo/Par lawsuit against FDA involves seeking a judicial determination about whether FDA’s inclusion of vasopressin (the active ingredient in Endo/Par’s FDA-approved drug product Vasostrict®) on FDA’s Section 503B Bulks List is appropriate. Endo/Par’s lawsuit also seeks a determination concerning whether FDA’s 2017 Section 503B Bulk Substances Interim Policy violates the Administrative Procedures Act’s notice and comment rulemaking requirements. Recall that Endo/Par stated in a press release earlier this year that, based on FDA’s January 2018 public statements reflecting the Agency’s “intent to alter its compounding policy and comply with the DQSA, as well as subsequent discussions among the parties’ counsel, Endo previously agreed to FDA’s request to stay the litigation until March 30, 2018.” (See Press Release here). After FDA’s publication of new draft guidance revisiting the 503B bulks nomination process in March 2018 and discussions between the parties, Endo/Par agreed to extend the stay of the lawsuit for an additional 180 days as “FDA works toward implementation of the new compounding policy.” Under the terms of the proposed stay, Endo stated that it “will retain the ability to terminate the stay by notifying FDA that it believes that an entity has commenced or is likely to commence bulk compounding of any vasopressin-containing drug product under Section 503B.” Most interestingly, FDA released a new Bulks List on July 25, 2018, here, which list still includes vasopressin on Bulks List 1.

FDA’s March 2018 draft guidance indeed seeks significant changes to the nomination process for bulk substances for use in Section 503B Outsourcing Facilities. FDA’s proposed changes come almost six years after implementation of the Drug Quality and Security Act (Title 1), which created Outsourcing Facilities, and almost four years after FDA published its detailed bulk substances interim policy… pursuant to which the compounding industry nominated hundreds and hundreds of bulk substances, and after FDA, with the assistance of the Pharmacy Compounding Advisory Committee (PCAC) already made determinations concerning the propriety of using those substances in compounded medications. After receiving a nomination for the bulk substance vasopressin, FDA added that substance to the list in the summer of 2017. That listing decision led to the Endo/Par lawsuit against FDA described above.

Next enters Athenex and its Motion for Intervention in the Endo/Par litigation. Evidently it was Athenex’s nomination for vasopressin that FDA reviewed (and thus added the substance to Bulks List 1) last July. Athenex’s Memorandum in Support of its Motion to Intervene describes the Company’s significant investment in, and commitment to, its 503B outsourcing facility operations, and its flagship compounded formulations, including ready-to-use vasopressin products. It also describes in detail how Athenex has devoted considerable financial and other resources to preparing compounded vasopressin products in reliance on FDA’s 2017 inclusion of the substance on Bulks List 1.

Athenex also notes that vasopressin been used intravenously in hospitals, mostly in emergency scenarios, from almost 100 years. Notwithstanding, Athenex alleges that after Par received FDA approval for its product, Par “leveraged its exclusivity to maximize sales,” and the “average wholesale price of intravenous vasopressin surged 3141% — from $4.27 to $148.40 per vial. (Memorandum in Support at 8, 21). From 2013 to the present, annualized sales increased from $4 to $400 million. We have heard this very familiar sounding Shkrellianesque tale through the years…but will the pricing trevails move the Court? Athenex also describes the many differences between the FDA-approved version (Vasostrict®) and compounded formulations of vasopressin, including the ready-to-use compounded form offered by Athenex.

In addition to other arguments supporting its intervention in the lawsuit, Athenex argues that compounding from bulk substances (nonsterile-to-sterile compounding) is safer than compounding using the approved product (i.e., using Vasostrict® in a sterile-to-sterile compounding process). And, it claims that, contrary to Endo/Par’s allegations, compounding with vasopressin is not unsafe and there is a clinical need for the compounded product. Athenex argues that because answers to these issues are also “central” to deciding the underlying lawsuit, the district court should grant its motion to intervene.

For those in the continuing compounding regulatory fray, these latest events are noteworthy. The Motion is, in turn, supportive of FDA’s efforts in the nomination process, and one could argue defends the Agency’s prior actions (and considerable efforts) involving its earlier bulks list determinations. It also challenges whether Endo/Par’s lawsuit is appropriate on its face because FDA’s earlier interim bulks policy is not “final agency action” upon which the lawsuit may be based. Furthermore, it states FDA’s decisions on bulk substance nominations to date, in particular the Agency’s exercise of enforcement discretion, is not reviewable by a court, at least at this point. Stay tuned for updates on this continuing saga.