109 F. Supp. 3d 104
D.D.C.2015Background
- Veloxis submitted a 505(b)(2) NDA for Envarsus XR (once-daily, extended-release tacrolimus) seeking approval for prophylaxis of organ rejection in de novo and conversion kidney transplant patients; FDA gave tentative approval but withheld final approval for the de novo indication because of exclusivity held by Astellas’s Astagraf XL.
- Astagraf XL (a once-daily, extended-release tacrolimus) received full FDA approval based on two clinical studies (Study 158 and Study 12-03) and was granted three-year marketing exclusivity for the conditions supported by those new clinical investigations, expiring July 2016.
- Veloxis argued the FDA erred in delaying Envarsus XR approval and violated the Administrative Procedure Act; parties cross-moved for summary judgment and asked the court to review the agency record under the APA (arbitrary-and-capricious standard, with Chevron deference where statutory interpretation implicated).
- Central statutory provisions: Hatch-Waxman exclusivity scheme and QI Act amendments extending three-year exclusivity to certain “old antibiotics” submitted after Oct. 8, 2008; key statutory language at 21 U.S.C. § 355(c)(3)(E)(iii).
- FDA rationale: Astagraf XL was a post-2008 resubmission entitled to three-year exclusivity; Envarsus XR shares Astagraf XL’s exclusivity-protected “conditions of approval” (once-daily, extended-release tacrolimus for de novo patients), so FDA may not make a second 505(b)(2) NDA effective for those conditions until exclusivity expires.
Issues
| Issue | Plaintiff's Argument | Defendant's Argument | Held |
|---|---|---|---|
| Whether a withdrawn pre-2008 NDA that was later resubmitted qualifies for QI Act three-year exclusivity | Veloxis: Astagraf XL was pending before Oct. 2008 so cannot get QI exclusivity | FDA: the pre-2008 submission was withdrawn; a new post-2008 Astagraf XL NDA was submitted and supports exclusivity | Court: FDA reasonably awarded exclusivity to the post-2008 resubmitted Astagraf XL; grant defendants SJ |
| Meaning of “relied upon” in 21 U.S.C. § 355(c)(3)(E)(iii) — must a second 505(b)(2) NDA rely on the same clinical studies to be blocked? | Veloxis: “Relied upon” requires overlap in clinical investigations; Envarsus XR did not rely on Astagraf XL’s new studies, so should not be blocked | FDA: “Relied upon” distinguishes 505(b)(2) from 505(b)(1); exclusivity blocks approvals that share conditions of approval regardless of which studies a 505(b)(2) sponsor relied on | Court: Statute interpreted to block a second-in-time 505(b)(2) NDA when it shares exclusivity-protected conditions of approval; FDA’s reading is reasonable and entitled to deference |
| Scope of “conditions of approval” protected by three-year exclusivity — do Astagraf XL and Envarsus XR share those conditions? | Veloxis: numerous clinically meaningful differences exist; Envarsus XR is not covered by Astagraf XL’s exclusivity scope | FDA: exclusivity covers the innovations supported by Astagraf XL’s new trials (once-daily, extended-release tacrolimus for de novo patients); Envarsus XR seeks the same condition | Court: Astagraf XL’s exclusivity covers the once-daily extended-release de novo indication; Envarsus XR shares that condition; approval properly delayed |
| Whether Veloxis may challenge FDA’s characterization of Study 158 as a "new clinical investigation" on judicial review | Veloxis: Study 158 was not a new clinical investigation essential to Astagraf XL’s approval | FDA: Veloxis waived that argument by not raising it before the agency after receiving notice | Court: Veloxis waived the challenge (plaintiff had notice via FDA exclusivity summary and opportunities to raise the issue); claim forfeited |
Key Cases Cited
- Chevron U.S.A., Inc. v. Natural Res. Def. Council, Inc., 467 U.S. 837 (agency statutory interpretation framework)
- Motor Vehicle Mfrs. Ass’n v. State Farm Mut. Auto. Ins. Co., 463 U.S. 29 (arbitrary-and-capricious standard)
- AstraZeneca Pharms. LP v. FDA, 872 F. Supp. 2d 60 (deference to FDA on scope of exclusivity for changes supported by new clinical studies)
- ViroPharma, Inc. v. Hamburg, 898 F. Supp. 2d 1 (QI Act and exclusivity for old antibiotics)
- Teva Pharms. Indus., Ltd. v. FDA, 355 F. Supp. 2d 111 (presumption of administrative regularity and deference to FDA in FDCA interpretation)