FDA OKs First Once-Daily IV COX-2 Preferential NSAID for Pain

The US Food and Drug Administration (FDA) has approved meloxicam injection (Anjeso, Baudax Bio) for the treatment of moderate to severe pain in adults, either by itself of with other nonsteroidal anti-inflammatory drug (NSAID) analgesics, according to a company news release.

Meloxicam injection will be given as a once-daily intravenous bolus push.

Meloxicam is a long-acting, preferential cyclooxygenase type 2 (COX-2) pathway inhibitor with analgesic, anti-inflammatory, and antipyretic properties that are thought to result from inhibition of the COX-2 pathway and reduced prostaglandin biosynthesis.

The onset of analgesia with meloxicam injection is delayed, and the drug should not be used when rapid onset of analgesia is needed.

"The approval of Anjeso marks an important achievement for the medical community given the unmet need for non-opioid options in the pain treatment landscape," Keith Candiotti, MD, chair of the Department of Anesthesiology, Perioperative Medicine and Pain Management at the University of Miami, Florida, said in the news release.

"While traditional opioid medications have proven effective at providing pain relief, the associated adverse side effects, including sedation and respiratory depression, have driven physicians to employ a multi-modal approach to treating post-operative pain. With 24-hour, durable pain relief and a safety profile comparable to placebo, Anjeso has the potential to serve as a meaningfully differentiated analgesic alternative," he continued.

The approval follows consideration of data from two phase 3 efficacy trials and one phase 3 safety study. The new drug application also included data from four phase 2 clinical trials and other safety studies.

"The safety and efficacy of Anjeso have been well-established through several mid- and late-stage clinical studies," Stewart McCallum, MD, chief medical officer of Baudax Bio, said in the news release. "Moreover, data from our Phase III safety trial demonstrated that Anjeso is well tolerated and impacted opioid consumption compared to placebo, further highlighting its value to patients, providers and health systems."

Phase 3 Efficacy Trials

The first efficacy trial was a multicenter, randomized, double-blind, placebo-controlled study that included 201 patients who had undergone bunionectomy. Patients were randomly assigned in a 1:1 ratio to receive up to three 30-mg meloxicam injections or placebo once every 24 hours after surgery.

Those who received meloxicam experienced a statistically significant reduction in sum of the pain intensity differences over 48 hours (SPID48) (P = .0034) compared with those who received placebo.

The study met 15 of the 19 secondary outcomes, "including statistically significant differences in SPID6 (p = 0.0153), SPID12 (p = 0.0053), SPID24 (p = 0.0084), SPID24-48 (p = 0.0050), time to first use of rescue medication (p = 0.0076), and several other rescue use and pain relief metrics during the first 48 hours, compared to placebo," the company noted in the news release.

The second study was a multicenter, randomized, double-blind, placebo-controlled clinical trial that enrolled 219 patients who had undergone abdominoplasty. The patients were randomly assigned in a 1:1 ratio to receive meloxicam injection 30 mg or placebo once every 24 hours. Those in the meloxicam group experienced a statistically significant decrease in SPID24 (P = .0145) compared with those in the placebo group.

The trial met "statistical significance for 10 of the secondary endpoints, including statistically significant differences in SPID12 (p = 0.0434), time to perceptible pain relief (p = 0.0050), subjects with ≥ 30% improvement at 24 hours (p = 0.0178), number of times patients required rescue in the first 24 hours after randomization (p = 0.0275), as well as number of times rescued from 24 to 48 hours (p = 0.0009), and several other pain relief metrics, compared to placebo," according to the news release.

In both efficacy studies, meloxicam injection was well tolerated, and rates of serious adverse events related to bleeding did not differ between the meloxicam and placebo groups.

Safety Study

The safety study was a multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial that included patients who underwent major elective surgeries and were expected to remain hospitalized for at least 24 to 48 hours. The procedures included total hip and knee replacements, spinal surgeries, hernia repairs, gynecologic surgeries, and others.

Of the study participants, 40% were men, and 23% were older than 65 years. The safety trial did not require minimum pain scores for treatment. Study sites were allowed to use opioids and other pain management modalities, in accordance with their standard of care, with meloxicam or placebo added.

The study randomly assigned patients in a 3:1 ratio to receive either meloxicam or placebo intravenously once daily up to seven doses; 721 patients received one or more doses of the study medication.

In those aged 65 years or older, approximately 7% fewer patients in the meloxicam group experienced at least one adverse event compared with the placebo group. The percentage of study participants who experienced one or more serious adverse events was lower in the meloxicam group (2.6%) than in the placebo group (5.5%).

Two serious adverse events were considered to be possibly related to the study treatment. Both occurred in one patient in the placebo group. There were no deaths in either of the treatment groups. Approximately 3% of those in each study group discontinued the study.

Among the most frequent adverse effect experienced by at least 2% of patients who received meloxicam injection and that occurred at a higher frequency compared with placebo were constipation, increased gamma-glutamyl transferase, and anemia.

The product label includes warnings about an increased risk for serious and possibly fatal cardiovascular thrombotic events. It states that meloxicam injection is contraindicated in patients who are to undergo coronary artery bypass graft (CABG) surgery. Patients taking meloxicam injection also have an increased risk for potentially fatal serious gastrointestinal adverse events, such as "bleeding, ulceration, and perforation of the stomach or intestines."

These risks can be increased early in treatment and may increase as treatment goes on.

Meloxicam injection should not be used in those who are known to be hypersensitive to meloxicam or to any of the product's components; those with a history of asthma, urticaria, or other allergic reaction after using aspirin or other NSAIDs; those with moderate to severe renal insufficiency who are at risk for renal failure related to volume depletion; and in patients who are to undergo CABG surgery.

The company said in the release it expects to make Anjeso available to physicians and patients in late April or early May.

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