Pipeline & Approvals
Anakinra (Kineret) has been approved by the Food and Drug Administration (FDA) to treat adults and children with neonatal-onset multisystem inflammatory disease (NOMID), the most severe form of cryopyrin-associated periodic syndromes (CAPS).1 Prior to this approval, anakinra was available under an Orphan Drug Designation. This is its first approval for use in children. NOMID is associated with an overproduction of interleukin-1 (IL-1) that, when left untreated, leads to hearing and visual loss, cognitive dysfunction, joint contractures, bone loss, and cartilage loss.
Bazedoxifene/conjugated estrogen had its New Drug Application (NDA) filed on December 13, 2012.2 The FDA Prescription Drug User Fee Act (PDUFA) date is October 3, 2013. It was submitted for the treatment of moderate to severe vasomotor symptoms, vulvar and vaginal atrophy associated with menopause, and also to prevent postmenopausal osteoporosis in nonhysterectomized women. Bazedoxifene is a selective estrogen receptor modulator that has been studied in over 7,500 postmenopausal women in the Selective estrogens, Menopause And Response to Therapy (SMART) trials. The most common adverse reactions in clinical trials were abdominal pain, muscle spasms, and vaginal yeast infection.
Canakinumab (ACZ885) is a fully human monoclonal antibody that inhibits IL-1 beta. It is currently in phase III clinical trials for treating systemic juvenile idiopathic arthritis (SJIA).3 Recent data show that it led to substantial symptom relief in young patients with SJIA (n=84). In one trial known as beta-SPECIFIC 1, 84% of canakinumab-treated SJIA patients had at least a 30% improvement in symptoms (JIA ACR30) versus 10% of placebo-treated patients. This occurred after 15 days of treatment. This benefit continued beyond 29 days (P<0.001). This was a randomized, double-blind, placebo-controlled, four-week study. In beta-SPECIFIC 2, of 177 patients who were prescribed corticosteroids, 45% of canakinumab-treated patients were able to reduce their steroid use, with 33% of patients able to completely discontinue steroids. These patients were almost three times less likely to experience a new flare. Seventy-four percent of canakinumab-treated patients remained flare-free versus 25% of placebo-treated patients (P=0.003).
Fostamitinib is an oral spleen tyrosine kinase inhibitor currently in phase III clinical trials for the treatment of rheumatoid arthritis (RA).4 Fostamatinib blocks signalling in multiple cell types involved in inflammation and tissue degradation in RA and may delay disease progression. The phase III trials, the results of which are expected by mid-2013, are known as, Oral Syk Inhibition in Rheumatoid Arthritis (OSKIRA). Three pivotal studies are ongoing: two are examining fostamatinib in patients who have had an inadequate response to disease-modifying antirheumatic drugs (DMARDs). These trials, OSKIRA-1 and OSKIRA-2, are both 12-month studies; one six-month study, OSKIRA-3, is studying patients who have had an inadequate response to anti–tumor necrosis factor therapy. A long-term extension study will also examine ongoing tolerability and safety. The primary study endpoints of OSKIRA 1 to 3 include the proportion of patients with ACR20 response criteria versus placebo. The OSKIRA-1 study also has a co-primary endpoint of change from baseline to week 24 in the modified total Sharp score.