Etanercept Submitted for Chronic, Severe Plaque Psoriasis in Children
The U.S. Food and Drug Administration (FDA) has accepted the supplemental Biologics License Application for etanercept (Enbrel) for treating pediatric patients with chronic, severe plaque psoriasis.1 The application was submitted in early January 2016 and is based on results of a one-year Phase 3 study with a five-year open-label extension that evaluated the safety and efficacy in pediatric patients with plaque psoriasis.
The Prescription Drug User Fee Act (PDUFA) target action date for approval of this new indication is Nov. 5, 2016. If etanercept receives FDA approval, it will be the first systemic drug therapy approved in the U.S. to treat children with severe, chronic plaque psoriasis.
Novel Anti-RA Biologic Demonstrates Efficacy, Safety & Low Cost
Gerilimzumab is a novel anti-IL-6 cytokine antibody being used to treat inflammatory diseases, such as rheumatoid arthritis (RA).2 In two studies, gerilimzumab proved safe in very low doses of less than 50 mg (per patient per year) and infrequent dosing (one subcutaneous injection every eight weeks). These dosing levels may enable extremely low annual pricing—possibly as low as $2,000 per patient.
In one ascending dose study, gerilimzumab was administered at four dosages: 1 mg, 5 mg, 15 mg and 30 mg via subcutaneous injection. In a multiple-ascending dosing study, gerilimzumab was administered by subcutaneous injection at 5 and 20 mg doses, once monthly for three months. Both studies included 50 subjects and also evaluated safety and tolerability of gerilimzumab compared with placebo. In both studies, gerilimzumab was well tolerated, with no serious adverse events reported.
Gerilimzumab is expected to be submitted for a pivotal RA trial sometime this month (June 2016).
AXS-02 in a Phase 3 Clinical Trial for Knee OA
AXS-02 (disodium zoledronate tetrahydrate) is an osteoclast inhibitor currently in a Phase 3 clinical trial as a targeted, non-opioid oral therapy for managing chronic pain.3 Known as COAST-1 (Clinical Knee Osteoarthritis Symptom Treatment 1), the study is evaluating the safety and efficacy of disodium zoledronate tetrahydrate on pain in patients with knee osteoarthritis (OA).
Disodium zoledronate tetrahydrate has a high affinity for bone mineral and reduces osteoclast activity by inhibiting the farnesyl pyrophosphate synthase (FPPS) enzyme. The therapy is being developed to treat complex regional pain syndrome (CRPS) and knee OA pain associated with bone marrow lesions. It is also being investigated to treat chronic lower back pain.
Ixekizumab Receives FDA Approval for Plaque Psoriasis
Ixekizumab (Taltz) binds to interleukin (IL)-17A, suppressing inflammation. Ixekizumab is a humanized immunoglobulin G subclass 4 (IgG4) monoclonal antibody (mAb) with neutralizing activity against IL-17A. It has been approved by the FDA to treat adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.4 The treatment is available as an auto-injector and as a prefilled syringe.
Ixekizumab is administered subcutaneously at a dose of 160 mg or two 80 mg injections at Week 0, followed by 80 mg injections at Weeks 2, 4, 6, 8, 10 and 12. Patients then receive 80 mg ixekizumab every four weeks.5 In clinical trials, the most common adverse reactions were injection-site reactions, upper respiratory tract infections, nausea and tinea infections.
Belimumab May Reduce Steroid Use in SLE
In pooled data from two large randomized controlled clinical trials, belimumab, the B-lymphocyte stimulator (BLyS)-specific inhibitor, had a moderate association with a greater likelihood of steroid dose reduction over 52 weeks in patients with systemic lupus erythematosus (SLE).6
Compared with placebo-treated patients, dose reduction occurred in 39% of belimumab-treated patients compared to 31% of placebo-treated recipients. Dose augmentation occurred in 18% vs. 31% of belimumab- and placebo-treated patients, respectively. Steroid dose increase occurred in 23% of belimumab-treated patients vs. 35% of placebo-treated patients. The steroid doses decreased in more belimumab-treated patients (37%) than placebo-treated patients (30%).
Romosozumab Effective for Men & Women with Osteoporosis
The Phase 3 BRIDGE (placeBo-contRolled study evaluatIng the efficacy and safety of romosozumab in treatinG mEn with osteoporosis) study recently reported positive top-line results for romosozumab.7 Romosozumab works by inhibiting the protein sclerostin and has a dual effect on bone, both increasing bone formation and decreasing bone resorption.
In the BRIDGE study, men (n=245) were randomized 2:1 to receive either 210 mg romosozumab subcutaneously every month or placebo subcutaneously every month for 12 months. A statistically significant increase in bone mineral density (BMD) at Month 12 compared with placebo-treated patients in the lumbar spine as assessed by dual-energy X-ray absorptiometry was the primary endpoint achieved. The secondary endpoints were also met, which included statistically significant BMD increases at Month 12 at the femoral neck and total hip, as well as statistically significant BMD increases at Month 6 at the lumbar spine, femoral neck and total hip—all compared with placebo-treated patients.
The most frequently reported adverse effects occurring in more than 5% of romosozumab-treated patients were back pain, constipation, headache, hypertension and nasopharyngitis. Injection-site reactions occurred in 5.5% of romosozumab-treated patients and 3.7% of placebo-treated patients; most reactions were mild in severity.
The Phase 3 STRUCTURE (STudy evaluating effect of RomosozUmab Compared with Teriparatide in postmenopaUsal women with osteoporosis at high risk for fracture pReviously treated with bisphosphonatE therapy) study showed statistically significant increases in hip BMD and strength in postmenopausal women with osteoporosis transitioning from bisphosphonate treatment.
Participants were given 210 mg romosozumab once monthly and compared with those given 20 mcg teriparatide daily for 12 months.8 STRUCTURE included postmenopausal osteoporotic women (n=436) averaging 72 years, with a history of non-vertebral fracture after age 50 or vertebral fracture and treatment with bisphosphonate therapy for a minimum of three years prior to transitioning to romosozumab or teriparatide therapy. For secondary endpoints, romosozumab-treated patients had significantly greater increases in BMD from baseline and increases in strength compared with teriparatide-treated patients.
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.
- Amgen Inc. FDA accepts Amgen’s supplemental biologics license application for the expanded use of enbrel (etanercept) to treat pediatric patients with chronic severe plaque psoriasis. 2016 Mar 10.
- Bird Rock Bio Inc. Bird Rock Bio’s gerilimzumab, an anti-IL-6 antibody, demonstrates potential for affordable global access to a novel biologic to treat rheumatoid arthritis. 2016 Mar 16.
- Axsome Therapeutics Inc. Axsome Therapeutics initiates phase 3 study of AXS-02 for knee osteoarthritis associated with bone marrow lesions. 2016 Mar 28.
- U.S. Food and Drug Administration. FDA approves new psoriasis drug Taltz. 2016 Mar 22.
- U.S. Food and Drug Administration. Taltz label information. 2016 Mar 22.
- Swift D. Benlysta found steroid-sparing in lupus: Modest effects in prednisone dose reduction seen in post-hoc analyses. MedPage Today. 2016 Mar 26.
- UCB. UCB and Amgen announce positive topline results from phase 3 study evaluating romosozumab in men with osteoporosis. 2016 Mar 21.
- Amgen Inc. Amgen and UCB present positive data at ENDO 2016 comparing romosozumab with teriparatide. 2016 Apr 1.