Efficacy Data: Pivotal Trial Summary, Average Daily Pain, Additional Outcome Measures

Trial summary¹

ZILRETTA^® (triamcinolone acetonide extended-release injectable suspension) was studied in a multicenter, international, randomized, double-blind, parallel-arm, placebo- (saline) and active-controlled (TAcs) trial that evaluated patients with moderate to severe OA pain of the knee (N=484)
- Patients received a single intra-articular injection of ZILRETTA (32 mg, n=161), saline (n=162), or TAcs (40 mg, n=161) and were followed for up to 24 weeks, with daily pain reported and evaluations at baseline and at Weeks 4, 8, 12, 16, 20, and 24

Pivotal trial outcome measures:

Average daily pain (ADP): Measures daily pain intensity on a 0 to 10 numeric rating scale (NRS)

ADP=average daily pain; OA=osteoarthritis; TAcs=triamcinolone acetonide crystalline suspension.

Phase 3 study

Rapid, persistent, and proven relief from OA knee pain

Patients experienced a significant reduction in OA knee pain vs saline control after a single injection¹

Pain relief in patients with moderate to severe knee OA

Rapid—4 days median time to onset with ZILRETTA^® (triamcinolone acetonide extended-release injectable suspension) and 3 days with TAcs^1*
Substantial—50% reduction from baseline at Week 12¹
Persistent—reduction in ADP each week from Weeks 1 to 12, extending to Week 16^1,4

ADP=average daily pain; BL=baseline; LS=least squares; NRS=numeric rating scale; OA=osteoarthritis; SE=standard error; TAcs=triamcinolone acetonide crystalline suspension.

The majority experienced no/mild knee pain as early as Week 1 and sustained through Week 12⁴

Percentage of 161 ZILRETTA-treated patients experiencing no/mild knee pain at
Week 4 (21%/49%), Week 8 (22%/47%), and Week 12 (20%/49%), respectively⁴

~60% of patients experienced no/mild knee pain at Week 16³

NRS=numeric rating scale; OA=osteoarthritis.

ZILRETTA demonstrated significant improvement in ADP and WOMAC A pain scores in patients with unilateral OA vs TAcs²

ZILRETTA demonstrated significant (P<0.05) improvement in ADP intensity compared with saline control from Weeks 1 to 24 and with TAcs from Weeks 4 to 21

Safety was similar among treatment groups, with most being mild or moderate.

ZILRETTA demonstrated significant (P<0.05) improvements in WOMAC A scores compared with saline control on Weeks 4, 8, 12, and 24 and compared with TAcs on Weeks 4, 8, 12,
and 24

Results from a post hoc analysis of a ZILRETTA Phase 3 trial

ADP=average daily pain; LSM=least squares mean; OA=osteoarthritis; SE=standard error; TAcs=triamcinolone acetonide crystalline suspension; WOMAC=Western Ontario and McMaster Universities Osteoarthritis Index.

ZILRETTA significantly improved outcomes among patients who reported consistent moderate to severe OA pain in both ADP and WOMAC A scales³

Change from baseline in ADP score was significantly (P<0.05) improved with ZILRETTA compared with TAcs each week from Weeks 5 to 19 and compared with saline control each week from Weeks 1 to 20

ZILRETTA demonstrated statistically significant (P<0.05) improvements in WOMAC A scores compared with TAcs at Weeks 4, 8, and 12 and compared with saline control at Weeks 4, 8, 12, and 16
ZILRETTA reduced WOMAC A pain scores from baseline by as much as 59% (Week 4); the largest reduction in pain resulting from TAcs treatment was 46% (Week 4)

Results from a post hoc analysis of a ZILRETTA Phase 3 trial

*Moderate to severe pain defined as ADP scores ≥5 to ≤9 (per original inclusion criteria) and WOMAC A
scores ≥2.

ADP=average daily pain; TAcs=triamcinolone acetonide crystalline suspension; WOMAC=Western Ontario and McMaster Universities Osteoarthritis Index.

Among these consistent pain reporters, 28% of ZILRETTA patients reported no pain at Week 12, compared with 8% of TAcs patients³

Results persisted through Week 16 with ~20% of patients treated with ZILRETTA experiencing no pain compared to ~9% for TAcs.

Results from a post hoc analysis of a ZILRETTA Phase 3 trial

ADP-intensity scores rated on a 0-10 NRS, with 0 indicating “no pain” and 10 indicating “pain as bad as you can imagine.”

ADP=average daily pain; NRS=numeric rating scale; TAcs=triamcinolone acetonide crystalline suspension.

Indication and Important Safety Information

Indication

ZILRETTA^® (triamcinolone acetonide extended-release injectable suspension) is indicated as an intra-articular injection for the management of osteoarthritis pain of the knee.

Limitation of Use: The efficacy and safety of repeat administration of ZILRETTA have not been demonstrated.

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. Serious events have been reported with epidural and intrathecal administration of corticosteroids and none are approved for this use. ZILRETTA should not be considered safe for epidural or intrathecal administration.
Hypersensitivity Reactions: Rare instances of anaphylaxis, including serious cases, have occurred in patients with hypersensitivity to corticosteroids.
Joint Infection and Damage: A marked increase in pain accompanied by local swelling, restriction of joint motion, fever, and malaise are suggestive of septic arthritis. Examine joint fluid to exclude a septic process. If diagnosis is confirmed, institute appropriate antimicrobial therapy. Avoid injecting corticosteroids into a previously infected or unstable joint. Intra-articular administration may result in damage to joint tissues.
Increased Risk of Infections: Infection with any pathogen in any location of the body may be associated with corticosteroid use. Corticosteroids may increase the susceptibility to new infection and decrease resistance and the ability to localize infection.
Alterations in Endocrine Function: Corticosteroids can produce reversible hypothalamic-pituitary-adrenal axis suppression, with potential for adrenal insufficiency after withdrawal of treatment, which may persist for months. In situations of stress during that period, institute corticosteroid replacement therapy.
Cardiovascular and Renal Effects: Corticosteroids can cause blood pressure elevation, salt and water retention, and increased potassium excretion. Monitor patients with congestive heart failure, hypertension, and renal insufficiency for edema, weight gain, and electrolyte imbalance. Dietary salt restriction and potassium supplementation may be needed.
Increased Intraocular Pressure: Corticosteroid use may be associated with increased intraocular pressure. Monitor patients with elevated intraocular pressure for potential treatment adjustment.
Gastrointestinal Perforation: Corticosteroid administration may increase risk of gastrointestinal perforation in patients with certain GI disorders and fresh intestinal anastomoses. Avoid corticosteroids in these patients.
Alterations in Bone Density: Corticosteroids decrease bone formation and increase bone resorption. Special consideration should be given to patients with or at increased risk of osteoporosis prior to treatment.
Behavior and Mood Disturbances: Corticosteroids may cause adverse psychiatric reactions. Prior to treatment, special consideration should be given to patients with previous or current emotional instability or psychiatric illness. Advise patients to immediately report any behavior or mood disturbances.

Adverse Reactions

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

Please see full Prescribing Information.

Efficacy data

Trial summary1

Phase 3 study

Rapid, persistent, and proven relief from OA knee pain

The majority experienced no/mild knee pain as early as Week 1 and sustained through Week 124

ZILRETTA demonstrated significant improvement in ADP and WOMAC A pain scores in patients with unilateral OA vs TAcs2

Results from a post hoc analysis of a ZILRETTA Phase 3 trial

ZILRETTA significantly improved outcomes among patients who reported consistent moderate to severe OA pain in both ADP and WOMAC A scales3

Results from a post hoc analysis of a ZILRETTA Phase 3 trial

Among these consistent pain reporters, 28% of ZILRETTA patients reported no pain at Week 12, compared with 8% of TAcs patients3

Results from a post hoc analysis of a ZILRETTA Phase 3 trial

Trial summary¹

The majority experienced no/mild knee pain as early as Week 1 and sustained through Week 12⁴

ZILRETTA demonstrated significant improvement in ADP and WOMAC A pain scores in patients with unilateral OA vs TAcs²

ZILRETTA significantly improved outcomes among patients who reported consistent moderate to severe OA pain in both ADP and WOMAC A scales³

Among these consistent pain reporters, 28% of ZILRETTA patients reported no pain at Week 12, compared with 8% of TAcs patients³