Flexion Therapeutics Enrolls First Patient in Phase 3 Trial of ZILRETTA® (triamcinolone acetonide extended-release injectable suspension) in OA of the Hip and Reports Results from SHIP Study

• First patient enrolled in Phase 3 hip OA registration trial in late December 2018; trial expected to complete in 2020
  
• Positive results from Phase 2 pharmacokinetics (PK) study of ZILRETTA in OA of shoulder and hip showed PK profiles consistent with previous studies in knee
• Additional Phase 2 studies of shoulder OA and adhesive capsulitis (frozen shoulder) are planned for second half of 2019

BURLINGTON, Mass., Jan. 02, 2019 (GLOBE NEWSWIRE) -- Flexion Therapeutics, Inc. FLXN today announced that, on December 26, 2018, the first patient was enrolled in a Phase 3 clinical trial to evaluate the safety and efficacy of ZILRETTA (triamcinolone acetonide extended-release injectable suspension) in patients with hip osteoarthritis (OA). Similar to knee OA, hip OA is a degenerative disease which has no cure, and it is estimated that roughly 25% of the U.S. population may develop symptomatic hip OA in their lifetime.¹

The initiation of the Phase 3 hip registration trial was supported by findings from a Phase 2, randomized, open-label, pharmacokinetic (PK) study in the shoulder and hip joints, known as the SHIP study. The results from the SHIP study demonstrated that ZILRETTA was generally safe and well tolerated, and the PK profile of ZILRETTA observed in both joints was consistent with previous PK studies in the knee. Results also showed that an injection of ZILRETTA into the hip resulted in 6-fold lower peak plasma levels and reduced systemic exposure compared to immediate-release triamcinolone acetonide in crystalline suspension (TAcs). The data on the hip cohort have been submitted for presentation.

"Like OA of the knee, OA of the hip is a serious disease that can profoundly affect one's quality of life. These impacts are compounded by the fact that there are so few non-surgical treatment options available to manage OA hip pain, and we believe ZILRETTA may be able to play an important role in helping these patients find meaningful pain relief," said Michael Clayman, M.D., President and Chief Executive Officer of Flexion. "We look forward to reporting the Phase 3 results with the expectation that the trial will read out in 2020."

The double-blind, placebo-controlled Phase 3 trial will evaluate the efficacy and safety of ZILRETTA in 440 patients with hip OA pain. Patients will be randomized to one of two treatment groups (1:1) and treated with a single intra-articular (IA) injection of either ZILRETTA or normal saline (placebo). The primary endpoint of the trial is the magnitude of pain relief versus placebo as measured on the WOMAC A (pain) subscale at Week 12.²

Following initial injection of ZILRETTA or placebo, participants will be evaluated at Weeks 12, 16, 20 and 24 to determine if a second IA injection for hip OA pain is clinically indicated. If eligible for a second injection, patients will receive open label ZILRETTA at the time of recurrent symptoms and will be followed for 12 weeks after that injection. Patients who do not receive a second injection will be followed for up to 24 weeks after their first injection.

Flexion also plans to initiate additional Phase 2 studies of ZILRETTA in the shoulder later this year. The company intends to initially investigate ZILRETTA in both OA of the shoulder and adhesive capsulitis (frozen shoulder).

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 Hip
OA, also known as degenerative joint disease, affects more than 30 million Americans and accounts for more than $185 billion in annual expenditures. It is estimated that roughly 25% of the population may develop symptomatic hip OA in their lifetime.¹ Despite the prevalence of hip OA, there are very few non-surgical treatment options; however, the clinical practice guideline from American Academy of Orthopaedic Surgeons (AAOS) notes strong evidence supporting the use of corticosteroid injections to improve function and reduce pain in the short-term for patients with symptomatic hip OA.³

About Flexion Therapeutics
Flexion Therapeutics 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 release regarding matters that are not historical facts, including, but not limited to, statements relating to the future of Flexion; the expected scope and design of the Phase 3 clinical trial of ZILRETTA for hip OA; Flexion's plans to initiate additional Phase 2 clinical trials evaluating ZILRETTA in shoulder OA and adhesive capsulitis; expected timing with respect to clinical trials, regulatory filings and development milestones; expected prevalence of OA of the hip; and the potential therapeutic and other benefits of ZILRETTA, 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, risks associated with designing and conducting clinical trials, including risks of delays or clinical holds; risks associated with developing and obtaining regulatory approval for product candidates; the fact that results of past clinical trials may not be predictive of subsequent trials; risks associated with commercializing new pharmaceutical products in the United States;  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 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.  

References

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2998063/
2. 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. 
3. https://www.aaos.org/uploadedFiles/PreProduction/Quality/Guidelines_and_Reviews/OA%20Hip%20CPG_1.5.18.pdf

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