Rheumatology Drug Updates: Abaloparatide Promising for Osteoporosis, Plus Secukinumab for Ankylosing Spondylitis

Abaloparatide for Osteoporosis

Abaloparatide is completing Phase III clinical trials for the potential treatment of postmenopausal osteoporosis in women who are at an increased risk of fracture.¹ Abaloparatide is a synthetic peptide that engages the parathyroid hormone receptor and has favorable bone building activity. Abaloparatide has completed Phase 3 development for use as a daily self-administered injection (abaloparatide-SC). The New Drug Application for abaloparatide-SC was submitted to the U.S. Food and Drug Administration at the end of the first quarter of 2016. The Prescription Drug User Fee Act date of March 30, 2017, has been set for this agent’s review.

Results from the Phase 3 double-blind, randomized, controlled, ACTIVE (Abaloparatide Comparator Trial In Vertebral Endpoints) trial were recently published in the Journal of the American Medical Association.² This clinical trial enrolled 2,463 patients to evaluate the safety and efficacy of abaloparatide for treating postmenopausal women with osteoporosis. Blinded, daily subcutaneous injections of placebo (n=821), 80 μg abaloparatide (n=824) or 20 μg open-label teriparatide (n=818) were administered for 18 months.

The study enrolled women with bone mineral density T score ≤−2.5 and >−5.0 at the lumbar spine or femoral neck, and with radiological evidence ≥2 mild or ≥1 moderate lumbar or thoracic vertebral fracture, or a history of a low-trauma, non-vertebral fracture within the prior five years. Additionally, postmenopausal women over 65 years old with fracture criteria and a T score ≤−2.0 and >−5.0, or without fracture criteria and a T score ≤−3.0 and >−5.0, could also enroll. In all, 1,901 women completed the study.

Increases in bone mineral density were greater in the abaloparatide-treated patients than in placebo-treated patients (P<0.001). In addition, the incidence of hypercalcemia was lower in abaloparatide-treated patients (3.4%) compared with teriparatide-treated patients (6.4%). The results of this trial showed that patients treated daily with abaloparatide for 18 months had a significantly greater reduction in the incidence of new vertebral fractures (P<0.001) and non-vertebral fractures (P=0.049) compared with placebo.

A transdermal formulation of abaloparatide is also being evaluated in clinical trials for potential use as an osteoporosis treatment.¹

NICE Draft Guidance

New draft guidance from the National Institute for Health and Care Excellence (NICE) means patients in the U.K. with ankylosing spondylitis will have access to the interleukin (IL) 17A inhibitor, secukinumab (Cosentyx).³ Secukinumab was licensed for use in the U.K. in May and is the first in a new class of drugs to treat the condition. The drug helps reduce inflammation and pain, and improves mobility. It comes in pre-filled pen syringes for self-administration.

The draft guidance recommends secukinumab for treating patients with active ankylosing spondylitis in adults when non-steroidal anti-inflammatory drugs or TNF-alpha inhibitors have failed or are not recommended.

Tocilizumab Promising for sJIA

In a recent clinical trial, researchers in Japan evaluated the effectiveness and safety of tocilizumab in pediatric patients with systemic juvenile idiopathic arthritis (sJIA).⁴ Four hundred seventeen patients were enrolled in, and observed during, this 52-week study, the results of which were published in the Annals of Rheumatic Disease.

All new tocilizumab pediatric patients were enrolled and observed from April 2008–February 2012, and additional patients were drawn from participants who were involved in tocilizumab clinical trials. Patients had a median age of 11 years and a median disease duration of four to six years. Also, 48% of participants were female.

[Researchers in Japan concluded] that in these real-world patients, tocilizumab was well tolerated, effective & safe.

Concomitant conditions included respiratory disease, cardiac functional disorders, liver disorders, renal dysfunction, gastrointestinal tract disturbances and diabetes mellitus. Tocilizumab exposure was 407.0 patient-years. Patients received 8 mg/kg tocilizumab once every two weeks.

Researchers collected data on patient characteristics, adverse events and effectiveness parameters. Serious adverse events were higher than reported in previous studies (54.5/100 patient‑years), rates of serious infections were 18.2/100 patient‑years and total adverse events were 224.3/100 patient-years. The most common infection was bacterial pneumonia (10 patients, 2.9/100 patient‑years), while eight patients developed gastroenteritis. The second most common adverse events were respiratory, thoracic and mediastinal events with a rate of 34.9/100 patient-years. The systemic features most reported at baseline were fever and rash, occurring in about a third of patients. At baseline, 61% of patients had no systemic sJIA symptoms. Twenty-six macrophage activation syndrome events were reported in 24 patients (6.4/100 patient-years), three of whom had a history of macrophage activation syndrome. There were 14 infusion reactions.

The mean systemic feature score was based on the number of systemic manifestations present of eight sJIA parameters: rash; fever; cervical, axial or inguinal lymphadenopathy; hepatomegaly; splenomegaly; and serositis. The mean systemic feature score decreased from 1.6 at baseline to 0.2 at Week 52 (P<0.0001). At Weeks 4, 8 and 52, 91%, 96% and 99% of patients achieved normal C-reactive protein levels (<0.3 mg/dL), respectively.

The authors conclude that, in these real-world patients, tocilizumab was well tolerated, effective and safe. The higher serious adverse events and serious infection incidences may be due to concomitant disorders and corticosteroid use.

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.

References

1. Radius Health Inc. News release: JAMA publishes positive phase III data for abaloparatide in postmenopausal women with osteoporosis. 2016 Aug 16.
2. Miller PD, Hattersley G, Riis BJ, et al. Effect of abaloparatide vs. placebo on new vertebral fractures in postmenopausal women with osteoporosis: A randomized clinical trial. JAMA. 2016 Aug 16;316(7):722–733.
3. Staff. NICE draft guidance recommends new drug for people with ankylosing spondylitis. FirstWord Pharma. 2016 Aug 8.
4. Yokota S, Itoh Y, Morio T, et al. Tocilizumab in systemic juvenile idiopathic arthritis in a real-world clinical setting: Results from 1 year of post-marketing surveillance follow-up of 417 patients in Japan. Ann Rheum Dis. 2016 Sep;75(9):1654–1660.