Ocrelizumab, an investigational humanized anti-CD20 monoclonal antibody for treating RA given in combination with MTX, met its primary endpoint (an ACR20 response) in the first phase 3 trial, known as STAGE.6 In this trial, ocrelizumab was given to patients who had an inadequate response to MTX at both Weeks 24 and 48. STAGE was an international randomized, multicenter, three-arm, parallel-group, placebo-controlled study in over 1,000 patients with active RA. However, in March, Roche and Biogen announced the suspension of ocrelizumab clinical trials for the treatment of RA due to the safety signal of serious infections and opportunistic infections, including some deaths. It was determined that the benefits of using ocrelizumab for RA did not outweigh its risks.7
Explore This IssueMay 2010
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The fate of oxycodone/niacin (Acurox), an abuse-deterrent formulation to treat moderate to severe pain, will soon be decided.8 Niacin was added to this agent for the purpose of reducing oxycodone misuse.
Pirfenidone, an investigational agent to delay pulmonary function declines in patients with idiopathic pulmonary fibrosis, has been recommended for approval by an FDA advisory panel.9 Advisory committee members felt that the drug’s effect was modest and agreed that long-term follow-up would be needed to determine if the agent is able to extend patient survival. A final decision is expected soon.
A New Drug Application (NDA) was filed for sodium oxybate (JZP-6) for treating fibromyalgia.10 The target date for the FDA to complete its review is October 11, 2010. In clinical trials, sodium oxybate significantly decreased fatigue and pain and also improved sleep quality, daily functioning, and patient global impression of change. It was generally well tolerated, with only mild to moderate adverse effects such as nausea, dizziness, and headaches. It already has FDA approval for the treatment of excessive daytime sleepiness and cataplexy in adults with narcolepsy.
Tapentadol extended-release tablets have had their NDA filed. Tapentadol is a centrally acting oral analgesic which binds to the mu-opioid receptor and inhibits norepinephrine reuptake. It is being used to treat moderate to severe chronic pain in adults aged 18 years and older. Clinical trials studied this agent for treating osteoarthritis, low back pain, and in patients with diabetic peripheral neuropathic pain. The extended-release formulation has been designed to resist mechanical destruction that could cause abuse of the agent (e.g., crushing and chewing). An immediate-release tapentadol tablet (Nucynta) is already FDA approved and is a Schedule II agent.11
A supplemental NDA was filed with the FDA for tocilizumab for preventing structural joint damage assessed by radiograph, and improving physical functioning in adults with moderate to severely active RA.12 The Tocilizumab Safety and the Prevention of Structural Damage (LITHE) Study showed that when tocilizumab was combined with MTX, patients had significantly less joint damage at two years compared with patients that received MTX monotherapy. Physical functioning was improved at Weeks 52 and 104.
Oral bisphosphonates are undergoing a safety review related to reports of a possible increased risk of atypical subtrochanteric femur fractures.13 Some of these agents include risedronate (Actonel), ibandronate (Boniva), and alendronate (Fosamax). During this process, the FDA recommends that healthcare professionals be aware of the possible risk of this type of femur fractures in patients taking oral bisphosphonates, to continue to follow the prescribing recommendations in the label, to discuss the known benefits and potential risks of using oral bisphosphonates with patients, and to report any adverse reactions to the FDA’s MedWatch program.14