Drug Updates: Apremilast, Belimumab, and More

Canakinumab (ACZ885, rilonacept), an investigational interleukin 1–beta protein targeted monoclonal antibody, continues to meet endpoints in children with active systemic juvenile idiopathic arthritis (SJIA).⁸ These data show that in SJIA patients (n=177) aged one to 19 years that were initially treated with ACZ885 for eight weeks then randomized to continue receiving active treatment or placebo, 45% of active-treated patients substantially reduced their oral corticosteroid use within 28 weeks (one of the primary study endpoints). Additionally, active-treatment patients were nearly three times less likely to have a new disease flare compared with placebo-treated patients (75% versus 27%, respectively).

In another study, patients with acute gouty arthritis who were unable to take nonsteroidal antiinflammatory drugs (NSAIDs) or colchicine received canakinumab for six months. Canakinumab was superior to triamcinolone acetate in delaying the occurrence of new gout flares and reducing the number of flares.⁹ The incidence of adverse events was higher for canakinumab (63% and 70%) compared with triamcinolone acetonide (49% and 57%) in two studies. More serious adverse events occurred in canakinumab-treated patients, but no opportunistic infections developed. The FDA has asked the manufacturer to submit additional safety data for consideration. The New Drug Application (NDA) has already been submitted to the FDA.

Thirty-five drugs were approved in 2011.

Data from a small study of 28 patients with mild-to-moderate SLE was presented at ACR.¹⁰ Patients were given four doses of a vaccine against interferon alpha (IFN-α) which showed that the IFN-α signature (in excess in SLE patients) can be down regulated, in essence vaccinating patients against their own IFN-α. The vaccine is called IFN-α-Kinoid and it is a modified IFN-α that lacks IFN-α biological activity. The vaccine is formulated so that it is recognized by the patient’s immune system, which then makes antibodies against its own INF-α. So far, it is well tolerated without significant side effects. This is another early step in a potentially new but investigational therapeutic for SLE.

Lupuzor has been granted approval from the FDA to conduct phase III clinical trials with “fast track” status.¹¹ In a Phase IIa proof of concept trial, the decrease of anti-dsDNA antibodies as a surrogate marker for efficacy and IL-10 was measured to determine its mechanism of action. It is administered by subcutaneous (SC) injection, two weeks apart. Different doses are still being studied.¹²

Methylnaltrexone bromide had its supplemental NDA accepted for the treatment of opioid-induced constipation (OIC). It is a SC injection of a peripherally acting mu-opioid receptor antagonist which counteracts constipating effects of opioids in the gastrointestinal tract without affecting pain-relieving ability. This agent is already been FDA approved for treating OIC in patients with advanced illness receiving palliative care who have not had an adequate response from laxatives.^6-13