April 5, 2016, marks a revolutionary day in the treatment of autoimmune diseases: The U.S. Food and Drug Administration (FDA) approved an infliximab (Remicade) biosimilar, known as Inflectra (infliximab-dyyb). Infliximab-dyyb, which is administered by intravenous infusion, is the first biosimilar drug approved to treat rheumatic disease in the U.S.1
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Infliximab-dyyb has received approval for almost all of the indications of the reference product. These include:
- Adult patients and pediatric patients (ages 6 years and older) with moderate to severe active Crohn’s disease who have had an inadequate response to conventional therapy (but not pediatric ulcerative colitis [UC]);
- Adult patients with moderate to severe active UC who have had an inadequate response to conventional therapy;
- Patients with moderate to severe active rheumatoid arthritis in combination with methotrexate;
- Patients with active ankylosing spondylitis;
- Patients with active psoriatic arthritis; and
- Adult patients with chronic severe plaque psoriasis.
Prescribing information is already available on the FDA website at Drugs@FDA and in the Purple Book.2
In a statement released April 6, the ACR welcomed the introduction of biosimilars to the U.S. healthcare system.3 It is “hopeful that the decrease in cost resulting from the availability of safe and effective biosimilars in the U.S. will increase our patients’ access to life-changing therapies and improve their overall health.
“While America’s rheumatologists support the development of new biosimilar therapies, the safety of our patients remains our highest priority. As such, we encourage the FDA to continue to apply distinct names for future biosimilars, and to maximize clarity in the labeling of biosimilars, specifically with respect to their interchangeable status and the origins (reference drug vs. biosimilar) of clinical data upon which FDA approval is based.”
FX006 Meets Primary Endpoint for Knee OA
FX006 (Zilretta) is an intra-articular, non-opioid anti-inflammatory drug that has received a fast-track designation from the FDA.4 This intra-articular, sustained-release injection employs proprietary microsphere technology combining triamcinolone acetonide (TCA) with the polymer poly lactic-co-glycolic acid to provide persistent drug concentrations locally and prolong the duration of pain relief.
In a recent Phase 3, placebo-controlled, active-comparator trial, patients were randomized to receive one of three treatments (1:1:1): a single 40 mg FX006 injection, placebo or 40 mg TCA immediate-release injection. The primary study objective was to assess the magnitude of pain relief at Week 12 compared with placebo. The secondary objectives were to assess the magnitude and duration of pain relief and effect compared with placebo and immediate-release TCA.
FX006 met its primary endpoint at Week 12, demonstrating significant (P<0.0001), durable and clinically meaningful pain relief vs. placebo in patients (n=486) with moderate to severe knee osteoarthritis pain. Additionally, FX006 demonstrated statistically significant analgesia compared with placebo at Weeks 1–16, with active drug-treated patients obtaining an average of 50% pain reduction from baseline over Weeks 1–12. Additionally, FX006 achieved statistical significance on WOMAC A, B and C (pain, stiffness and function) through Week 12 compared with placebo and immediate-release TCA.
A New Drug Application submission is planned for the second half of this year.
Golimumab Improves Radiographic Progression
A recently published study in Arthritis Care & Research outlined the long-term outcomes of patients who did and did not achieve minimal disease activity during the GO-REVEAL trial.5 These patients (n=405) had psoriatic arthritis (PsA) and participated in the trial for up to five years.
The GO-REVEAL trial was a Phase 3 randomized, double-blind, placebo-controlled trial of golimumab for 24 weeks. After Week 24, patients received an open-label extension of subcutaneous golimumab injections of either 50 or 100 mg given once every four weeks for up to five years. Patients were allowed to continue their stable methotrexate dose. By Week 16, if there was less than a 10% improvement in a patient’s swollen and tender joint count, the patient dose was increased. Placebo-treated patients were increased to 50 mg golimumab every four weeks, and patients treated with 50 mg golimumab were increased to 100 mg golimumab every four weeks.
Of the 405 patients, 126 (31%) discontinued the study treatment by Week 252, mostly due to adverse events and disappointing therapeutic response. Patients who received golimumab vs. placebo at Week 14 (P<0.0001; 24% compared with 1%) and Week 24 (P<0.0001; 28% compared with 8%) had a significantly greater minimal disease activity attainment and a greater response. Baseline methotrexate use did not change these results. The Week 52 response was 42%, compared with 30% for placebo.
Overall, minimal disease activity was realized at least once by about half of golimumab-treated patients. No matter what treatment patients were initially randomized to receive, those patients who showed more improvement in at least three or four consecutive time points had significantly less radiographic progression and greater functional outcomes at five years compared with those who did not meet minimal disease activity criteria. These outcomes did not necessarily correlate with changes in skin involvement.
In this study, 50 or 100 mg subcutaneous golimumab every four weeks led to better long-term functional improvement, better radiographic outcomes and better patient global assessment in patients who attained persistent minimal disease activity.
Michele B. Kaufman, PharmD, CGP, RPh, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.
- U.S. Food and Drug Administration. News release: FDA approves Inflectra, a biosimilar to Remicade. 2016 Apr 5.
- U.S. Food and Drug Administration. Purple book: Lists of licensed biological products with reference product exclusivity and biosimilarity or interchangeability evaluations. 2016.
- American College of Rheumatology. Press release: Rheumatology community responds to FDA approval of Inflectra (infliximab-dyyb), a biosimilar to Remicade. 2016 Apr 6.
- Flexion Therapeutics Inc. News release: Flexion Therapeutics reports primary endpoint met in pivotal phase 3 trial of Zilretta in knee osteoarthritis. 2016 Feb 16.
- Kavanaugh A, van der Heijde D, Beutler A, et al. Radiographic progression of patients with psoriatic arthritis who achieve minimal disease activity in response to golimumab therapy: Results through five years of a randomized, placebo-controlled study. Arthritis Care Res (Hoboken). 2016 Feb;68(2):267–274. doi: 10.1002/acr.22576.