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Flexion Therapeutics Submits Supplemental New Drug Application (sNDA) for ZILRETTA® (triamcinolone acetonide extended-release injectable suspension)

sNDA aims to revise the product label with new data indicating repeat administration
of ZILRETTA was safe and well tolerated

BURLINGTON, Mass., Dec. 17, 2018 (GLOBE NEWSWIRE) -- Flexion Therapeutics, Inc. (Nasdaq:FLXN) today announced it submitted a supplemental new drug application (sNDA) to the U.S. Food and Drug Administration (FDA) to revise the product label for ZILRETTA (triamcinolone acetonide extended-release injectable suspension). The sNDA is based on data from an open-label Phase 3b clinical trial, which indicated that repeat administration of ZILRETTA for treatment of osteoarthritis (OA) knee pain was safe and well tolerated with no deleterious impact on cartilage or joint structure observed through X-ray analysis.

“We believe the results from this trial clearly demonstrate that repeat administration of ZILRETTA was safe, well tolerated and devoid of deleterious effects on joint architecture. In addition, exploratory efficacy data indicated that patients experienced a consistent magnitude of pain relief from both the first and second injection. Taken together, we believe these results support modifying the label to reflect this experience and to remove current language referencing any limitation to repeat injection,” explained Michael Clayman, M.D., President and Chief Executive Officer of Flexion. “If approved, we believe this label change will give physicians clarity and confidence about administering repeat injections of ZILRETTA for their patients confronting OA knee pain. We look forward to working with the FDA as it reviews the sNDA in the months ahead.”

The primary endpoint of the Phase 3b single-arm, open-label trial was the safety and tolerability of repeat administration of ZILRETTA in patients with symptomatic OA of the knee. The patients enrolled in the study generally had longstanding and extensive disease, with more than two-thirds of the participants presenting with Kellgren-Lawrence Grade 3 (37.5%) or Grade 4 (30.3%), the most radiographically severe form of OA. Participants received an initial intra-articular injection of ZILRETTA followed by evaluation at Weeks 12, 16, 20 and 24 to determine their eligibility for a second injection.

In the trial, 95% of patients (195/205) experienced clinical benefit (as determined by self-assessment and with the agreement of their physician) after initial injection of ZILRETTA and 92% of these patients (179/195) received a second injection on or after Week 12. The median time to a second injection was 16.6 weeks, with 74% of patients receiving their second administration of ZILRETTA between Weeks 16 and 24.

There were no serious adverse events related to ZILRETTA reported during the trial, and the patterns of treatment emergent adverse events were consistent with those reported in previous clinical studies of ZILRETTA. An analysis of X-rays taken at baseline and Week 52 showed no harmful effects on cartilage or joint structure, as no incidences of chondrolysis, osteonecrosis, insufficiency fractures or clinically significant subchondral bone changes were observed. The trial also indicated that the magnitude and duration of pain relief experienced by patients after both the first and second injections was similar to results from the pivotal Phase 3 trial.

Indication and Select Important Safety Information for ZILRETTA

Indication: ZILRETTA is indicated as an intra-articular injection for the management of osteoarthritis pain of the knee. It is not intended for repeat administration.

Contraindication: ZILRETTA is contraindicated in patients who are hypersensitive to triamcinolone acetonide, corticosteroids or any components of the product.

Warnings and Precautions:

  • Intra-articular Use Only: ZILRETTA has not been evaluated and should not be administered by epidural, intrathecal, intravenous, intraocular, intramuscular, intradermal, or subcutaneous routes. ZILRETTA should not be considered safe for epidural or intrathecal administration.
  • Serious Neurologic Adverse Reactions with Epidural and Intrathecal Administration: Serious neurologic events have been reported following epidural or intrathecal corticosteroid administration. Corticosteroids are not approved for this use.
  • Hypersensitivity reactions: Serious reactions have been reported with triamcinolone acetonide injection. Institute appropriate care if an anaphylactic reaction occurs.
  • Joint infection and damage: A marked increase in joint pain, joint swelling, restricted motion, fever and malaise may suggest septic arthritis. If this occurs, conduct appropriate evaluation and if confirmed, institute appropriate antimicrobial treatment.

Adverse Reactions: The most commonly reported adverse reactions (incidence ≥1%) in clinical studies included sinusitis, cough, and contusions.

Please see ZilrettaLabel.com for full Prescribing Information.

About ZILRETTA
On October 6, 2017, ZILRETTA was approved by the U.S. FDA as the first and only extended-release intra-articular therapy for patients confronting osteoarthritis-related knee pain. ZILRETTA employs proprietary microsphere technology combining triamcinolone acetonide — a commonly administered, short-acting corticosteroid — with a poly lactic-co-glycolic acid (PLGA) matrix to provide extended pain relief over 12 weeks.

About Osteoarthritis (OA) of the Knee
OA, also known as degenerative joint disease, affects more than 30 million Americans and accounts for more than $185 billion in annual expenditures. In 2016, more than 15 million Americans were diagnosed with OA of the knee and the average age of physician-diagnosed knee OA has fallen by 16 years, from 72 in the 1990s to 56 in the 2010s. The prevalence of OA is expected to continue to increase as a result of aging, obesity and sports injuries. Each year, more than 15 million Americans are treated for OA-related knee pain, and approximately five million OA patients receive either an immediate-release corticosteroid or hyaluronic acid intra-articular injection to manage their knee pain.

About Flexion Therapeutics
Flexion Therapeutics (Nasdaq:FLXN) is a biopharmaceutical company focused on the development and commercialization of novel, local therapies for the treatment of patients with musculoskeletal conditions, beginning with osteoarthritis, a type of degenerative arthritis. The company's core values are focus, ingenuity, tenacity, transparency and fun. For the past two years, Flexion has been named one of the Best Places to Work by the Boston Business Journal, and Flexion and a Top Place to Work in Massachusetts by The Boston Globe.

Forward-Looking Statements
This release contains forward-looking statements that are based on the current expectations and beliefs of Flexion. Statements in this release regarding matters that are not historical facts, including, but not limited to, statements relating to the future of Flexion; the potential outcome of Flexion’s sNDA submission; and the impact on the prescription and use of ZILRETTA if the sNDA is approved, are forward-looking statements. These forward-looking statements are based on management's expectations and assumptions as of the date of this release and are subject to numerous risks and uncertainties which could cause actual results to differ materially from those expressed or implied by such statements. These risks and uncertainties include, without limitation, the sNDA is not approved or results in changes to the ZILRETTA label that are different than our expectations; whether any changes to the ZILRETTA label impact physicians’ willingness to prescribe ZILRETTA; risks associated with commercializing new pharmaceutical products; risks regarding our ability to obtain adequate reimbursement from payers for ZILRETTA; risks related to the manufacture and distribution of ZILRETTA, including our reliance on sole sources of supply and distribution; risks related to key employees, markets, economic conditions, health care reform, prices and reimbursement rates; and other risks and uncertainties described in our filings with the Securities and Exchange Commission (SEC), including under the heading "Risk Factors" in our Quarterly Report on Form 10-Q for the quarter ended September 30, 2018 filed with the SEC on November 7, 2018 and subsequent filings with the SEC. The forward-looking statements in this release speak only as the date of this release, and we undertake no obligation to update or revise any of the statements. We caution investors not to place considerable reliance on the forward-looking statements contained in this press release.  

Contacts:

Scott Young
Vice President, Corporate Communications & Investor Relations
Flexion Therapeutics, Inc.
T: 781-305-7194
syoung@flexiontherapeutics.com

Julie Downs
Manager, Corporate Communications
Flexion Therapeutics, Inc.
T: 781-305-7137
jdowns@flexiontherapeutics.com

Monday, December 17, 2018 - 16:30