Drug Updates

New Drug Information

Belimumab (Benlysta) for the treatment of active, autoantibody-positive systemic lupus erythematosus (SLE) in patients who are receiving standard therapy has received a positive opinion from European regulators recommending its approval.¹ Belimumab is administered by intravenous infusion and is the first B-lymphocyte stimulator protein inhibitor to be approved by the U.S. Food and Drug Administration (FDA). The last SLE drugs to be FDA approved were hydroxychloroquine and corticosteroids.

The FDA has approved a combination, fixed-dose tablet formulation of the nonsteroidal antiinflammatory drug (NSAID) ibuprofen (800 mg) and the histamine-2 receptor blocker famotidine 26.6 mg (Duexis).² It is approved to treat osteoarthritis (OA) and rheumatoid arthritis (RA) in patients who may be at risk for upper gastrointestinal (GI) ulcers stemming from chronic NSAID use. This formulation was studied in more than 1,500 patients and reduced the incidence of gastric ulcers (GU) and duodenal ulcers over six months. In the Efficacy and Safety Study of HZT-501 in Reducing the Risk of Ibuprofen-Associated Ulcers (REDUCE-1) study, a statistically significant reduction in the incidence of GU was seen with this formulation compared with ibuprofen monotherapy (8.7% vs. 17.6%). In the REDUCE-2 study, the combination product had a statistically significant reduction in the incidence of upper GI ulcers compared with ibuprofen monotherapy (10.5% vs. 20.0%). Taking a product such as this tends to be more costly because the individual ingredients are available as generics. Perhaps that is why this formulation has an unconventional famotidine dose (compared with 10 mg, 20 mg, or 40 mg, which are already available on the market). Using the individual generic agents may be more beneficial and less costly in at-risk patients.

Ketorolac tromethamine nasal spray (Sprix) is now available for the treatment of moderate to moderately severe pain that requires an opioid-like analgesia.³ This new formulation of ketorolac is available as a single-day nasal spray bottle that delivers 15.75 mg of ketorolac per spray (in 100µL). Each 1.7-gm bottle contains eight sprays. For adults younger than 65 years, the recommended dose is one 15.75-mg spray in each nostril (31.5 mg) every six to eight hours for a maximum daily dose of 126 mg.⁴ For patients age 65 years and older, those that have renal impairment, and those that weigh less than 50 kg, the recommended dose is one 15.75-mg spray in one nostril every six to eight hours (the maximum dose is 63 mg). This ketorolac formulation has the same contraindications and warnings as other ketorolac products. The bottle should be discarded 24 hours after taking the first dose.

Tocilizumab (Actemra), an interleukin (IL)-6 receptor blocker, has been FDA approved to treat children age two years and older who have active systemic juvenile idiopathic arthritis.⁵ It can be used as monotherapy or in combination with methotrexate (MTX). In clinical trials, there were 112 patients aged 2 to 17 years who were treated with the drug. Patients either had an inadequate response to NSAIDs or corticosteroids or were not able to take them. Patients received tocilizumab infusions every two weeks, with 85% responding to the drug versus a 24% response rate to placebo. In the follow-up period, there were three cases of macrophage activation syndrome.

Pipeline Agents

ACZ885 (canakinumab), a fully human monoclonal antibody, is undergoing phase 3 clinical trials in patients with severe gouty arthritis.⁶ In two pivotal studies of more than 450 patients, canakinumab demonstrated superior pain relief and reduced the risk of new attacks by up to 68% compared with injectable triamcinolone acetonide.⁷ There is evidence that excessive production of IL-1β plays a role in the inflammatory process of gouty arthritis and related conditions. ACZ885 works by neutralizing IL-1β, thus inhibiting inflammation. The agent is currently approved in Europe and the United States to treat cryopyrin-associated periodic syndrome.

Certolizumab pegol (Cimzia) will undergo a head-to-head trial versus adalimumab (Humira) in a first-ever industry-sponsored study investigating two anti–tumor necrosis factor α (TNF-α) agents in treating RA.⁸ The study will include patients with moderate to severe RA who have not had an adequate response to MTX and are anti–TNF-α therapy naive.

EX101 (alendronate) has had its New Drug Application (NDA) filed for this new formulation of alendronate.⁹ EX101 is a buffered effervescent tablet of alendronate for once-weekly administration to treat postmenopausal women and increase bone mass in men with osteoporosis.

Fulranumab is currently in phase 2 clinical trials to improve pain and functioning in patients with moderate to severe knee and hip OA.¹⁰ It is a human recombinant monoclonal antibody against human nerve growth factor (NGF). According to results from the recent American Pain Society Annual Meeting in May, patients age 40 to 80 years had improvements in pain, functioning, and pain interference with sleep when they received the once monthly or bimonthly injection of fulranumab. These are recent study results; however, in December the FDA placed all agents in the anti-NGF class (including fulranumab) on hold because they may be associated with a possible increased risk of rapidly progressive OA or osteonecrosis, conditions which can lead to the need for joint replacements.¹¹ In May, the FDA released phase 2 trials of fulranumab to treat cancer pain.¹²

Lesinurad is a once-daily oral inhibitor of uric acid transporter 1 that is currently in phase 2 trials to treat hyperuricemia and gout.^13,14 At the May European League Against Rheumatism (EULAR) meeting in London, results of the phase 2 clinical trials were reported. Over one month, 87% of patients that received combination therapy with allopurinol and lesinurad 600 mg once daily had a rapid and sustained serum urate level lowering to below 6 mg/dL. In addition, patients that received allopurinol in combination with lower doses of lesinurad, 400 mg once daily and 200 mg once daily, had 76% and 71% reductions, respectively, compared with allopurinol monotherapy (28% reduction). The results were both clinically and statistically significant (P<0.001).

The manufacturer of oxycodone (Remoxy) has reported results of a clinical trial in individuals with a history of “getting high” from prescription pain medications and found that Remoxy is more difficult to abuse than OxyContin and OxyIR.¹⁵ This twice-daily, long-acting oxycodone formulation to treat moderate-to-severe pain contains a very thick liquid in a hard gelatin capsule intended to resist tampering that would lead to rapid oxycodone release. Patients were unable to chew it for more than 48 seconds even though they were allowed to chew it for up to 90 seconds. This was due to its unpleasant taste and texture. As reported in the March issue of The Rheumatologist, the NDA for this drug was resubmitted in late December 2010.¹⁶ The FDA is scheduled to make a decision on this agent by June 23.

A subcutaneous monoclonal anti–TNF-α nanobody, ozoralizumab (ATN-103), for treating active RA has completed phase 2 proof-of-concept trials.¹⁷ In the trials, it was administered as three different doses once monthly and two different doses every two months versus placebo. The highest dose of 80 mg, administered every four weeks, resulted in statistically significant improvements in ACR20 responses versus placebo at Week 16. Improvements in clinical scores, ACR50, ACR70, Disease Activity Score (DAS) 28, and EULAR response at this dose were seen at Week 16, as well. An open-label safety extension trial was also started and is expected to be completed in early 2012.

Evaluated results of pooled data from phase 3 clinical trials to treat fibromyalgia with sodium oxybate (JZP-6) were reported at the May American Pain Society Annual Meeting.¹⁸ The investigators concluded that these analyses showed that in fibromyalgia patients, the drug demonstrated efficacy for pain reduction whether or not disease severity was moderate or severe at baseline. There was a greater than or equal to 30% reduction in pain with sodium oxybate dosed at 4.5 gm and 6 gm (versus placebo-treated patients) in a greater proportion of patients with moderate and severe pain and moderate and severe disease activity. Sodium oxybate is not currently FDA approved for treating this condition, but is still an active pharmaceutical pipeline agent for this use.¹⁹

Results of the phase 3 clinical trials for tofacitinib, an oral janus kinase inhibitor, were recently reported at EULAR.²⁰ At six months, an ACR20 response was achieved in 58% of patients who received tofacitinib 10 mg twice daily (BID) in those who had not previously responded to disease-modifying antirheumatic drugs (DMARDs). Placebo-treated patients had a 31% response. Background DMARDs included MTX, leflunomide, sulfasalazine, hydroxychloroquine, penicillamine, and gold (as single and combination therapies). Significant improvements were also seen in the 5 mg BID tofacitinib-dosed group. Adverse events were mostly mild, and no new safety signals were reported. Multinational 12-month clinical trial results (n=792) showed ACR50 and ACR70 responses in 36.6% and 16.2% of patients, respectively, in the tofacitinib 10-mg BID group, versus 12.7% and 3.2%, respectively, for placebo-treated patients. These results were considered significant symptom improvements. Significant improvements compared with placebo were also observed in the DAS physician index and the Health Assessment Questionnaire Disease Index. According to researchers, significant ACR 20, ACR50, and ACR70 responses were seen after two weeks of therapy.

Michele Kaufman is a freelance medical writer based in New York City and a clinical pharmacist at New York Downtown Hospital.

New Drug Information

Pipeline Agents

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Drug UPDATES

Drug UPDATES

Drug Updates

Drug Updates

New Drug Information

Pipeline Agents

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