Flexion Therapeutics Announces Publication of Data from Repeat Administration Trial of ZILRETTA® (triamcinolone acetonide extended-release injectable suspension) in Rheumatology and Therapy

• Results from Phase 3b clinical trial indicate that repeat administration of ZILRETTA for osteoarthritis (OA) knee pain was generally safe and well-tolerated
  
  
• X-ray data at baseline and Week 52 showed ZILRETTA had no deleterious impact on cartilage or joint structure   
• The majority (74%) of participants received their second injection at Week 16 or later and the magnitude of pain relief was similar for both injections
• Enrolled patients were approximately evenly distributed amongst Kellgren-Lawrence (KL) Grade 2, 3 and 4, and clinical benefit was similar across groups

BURLINGTON, Mass., Feb. 11, 2019 (GLOBE NEWSWIRE) -- Flexion Therapeutics, Inc. (Nasdaq:FLXN) today announced that the results from an open-label Phase 3b clinical trial evaluating the safety and exploratory efficacy of repeat administration of ZILRETTA (triamcinolone acetonide extended-release injectable suspension) in patients with osteoarthritis (OA) of the knee were published in . The data indicate that repeat administration of ZILRETTA was generally safe and well-tolerated. In addition, an analysis of radiographs (X-rays) taken at baseline and Week 52 showed ZILRETTA had no deleterious effects on cartilage or joint structure. The data also indicate that the magnitude and duration of pain relief experienced by patients after both the first and second injections was similar to the clinical benefit of ZILRETTA in the pivotal on which the FDA approval of ZILRETTA was based. The repeat administration study is the first to evaluate the effect of ZILRETTA in patients with the most advanced radiographic knee OA (Kellgren-Lawrence grade 4), demonstrating similar benefit compared to those with less advanced disease (KL-2 and 3).

“This valuable study suggests that repeat administration of ZILRETTA can provide patients suffering from knee OA consistent, substantial, and durable pain relief, and is generally well-tolerated. Importantly, analysis of the X-ray data showed no impact on cartilage or any other negative structural impact at one-year follow-up,” said Andrew Spitzer, M.D., Co-Director, Joint Replacement Program, Cedars-Sinai Orthopaedic Center. “Because OA knee pain can be chronic and debilitating, patients need treatments that can provide extended and effective relief. The data published in Rheumatology and Therapy suggest that ZILRETTA can play an integral role in helping patients manage recurring OA knee pain.”

Key topline results from the Phase 3 trial:

• Repeat administration of ZILRETTA appeared safe and well-tolerated, with no serious adverse events or discontinuations related to ZILRETTA;
  
  -  The most commonly reported adverse events were consistent with those reported in previous clinical studies of ZILRETTA.
• X-rays conducted at baseline and Week 52 showed ZILRETTA had no deleterious impact on cartilage or joint structure and there were no observations of chondrolysis, osteonecrosis, insufficiency fractures or clinically significant subchondral bone changes;
• The median time to a second injection was 16.6 weeks, with 25.1%, 33.5%, 20.7% and 20.1% of patients receiving their second injection at Week 12, 16, 20 and 24, respectively; and
• Among those who received two injections, the magnitude and duration of clinical benefit after the first and second injections were similar with marked numeric improvements from baseline in pain scores observed when first assessed at four weeks.
  
  -  More than two-thirds of patients experienced a ≥50% reduction in WOMAC-A pain at Week 4 following both the first and second injection.

“We are excited to have these data published in a peer-reviewed journal, as they provide meaningful clinical evidence that repeat administration of ZILRETTA appears to provide safe and effective pain relief for the millions of people who confront ongoing pain from OA of the knee,” explained Michael Clayman, M.D., President and Chief Executive Officer of Flexion. “In December, we provided the full data set from this repeat administration trial to the FDA as part of a supplemental New Drug Application (sNDA), and we look forward to working with the Agency as they conduct their review.” 

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 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. The pivotal Phase 3 trial on which the approval of ZILRETTA was based showed that ZILRETTA significantly reduced knee pain for 12 weeks, with some people experiencing pain relief through Week 16.  

About the Repeat Administration Trial 

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 including those with advanced disease. More than two-thirds of the participants presented 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. A second dose was administered only when patients reported they were ready for additional treatment (based on pain levels) and their physician agreed it was clinically indicated. Clinical benefit was measured through validated instruments including the WOMACⁱ questionnaire that evaluates a patient’s pain, stiffness and function, and the Knee Injury and Osteoarthritis Outcome Score-Quality of Life scale.

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 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 press release regarding matters that are not historical facts, including, but not limited to, statements relating to the future of Flexion; ZILRETTA's market potential and potential benefits; and expected increases in the rate of individuals with OA of the knee, are forward-looking statements. These forward-looking statements are based on management's expectations and assumptions as of the date of this press 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 risk that 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 in the United States; the risk that we may not be able to successfully maintain an effective sales force or product supply to commercialize ZILRETTA; competition from alternative therapies; the risk that we may not be able to maintain and enforce our intellectual property, including intellectual property related to ZILRETTA; the risk that ZILRETTA may not be successfully commercialized, including as a result of limitations in ZILRETTA's label and package insert information; 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; the risk that we may use our capital resources in ways that we do not currently expect; 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 press release speak only as of the date of this press 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

Julie Downs

Manager, Corporate Communications

Flexion Therapeutics, Inc.

T: 781-305-7137

ⁱ WOMAC (Western Ontario and McMaster Universities Arthritis Index) is a validated, widely used, proprietary set of standardized questionnaires used by health professionals to evaluate the condition of patients with osteoarthritis of the knee and hip, including pain, stiffness and physical functioning of the joints.