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
“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
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.
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.
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
Manager, Corporate Communications
Source: Flexion Therapeutics, Inc.