The approval is based on results from one of the largest studies conducted to date of hospitalized patients with cSSSI. The study showed that MERREM, administered 500 mg IV every eight hours, is a well-tolerated and effective treatment for patients with cSSSI, including the elderly and patients with diabetes mellitus.
"The FDA approval of MERREM represents a welcome therapeutic option for physicians who treat complicated skin and skin structure infections, which are more severe, can progress more rapidly, and pose a greater risk of spreading throughout the body than uncomplicated skin and soft tissue infections," said David Melnick, MD, senior medical director for infection and oncology at AstraZeneca Pharmaceuticals LP. "These infections can be caused by many different bacteria, including Gram-positive, Gram-negative, and anaerobic pathogens. Its broad spectrum of activity against a variety of disease-causing microorganisms makes MERREM a valuable agent for treating cSSSI in both adults and children. In addition, the pivotal trial demonstrates the excellent safety and efficacy profile of MERREM in patients with diabetes mellitus and supports
its use in patients with renal insufficiency, making MERREM an appropriate choice."
This international, Phase III, randomized, double-blind, multicenter clinical trial of 1,037 patients with complicated skin and skin structure infections compared the efficacy, safety and tolerability of MERREM, given at 500 mg IV every 8 hours, and imipenem-cilastatin given at 500 mg IV every eight hours. The primary efficacy end point was clinical outcome at follow-up in the clinically evaluable (CE) and modified intent-to-treat (MITT; patients who met eligibility criteria and received greater than or equal to one dose of study drug) populations.
The success rates in the CE patients at the follow-up visit were 86 percent in the MERREM arm and 83 percent in imipenem-cilastatin arm (95 percent CI, -2.8, 9.3) and 73 percent (MERREM) and 75 percent (imipenem-cilastatin; 95 percent CI, -8.4, 4.7) in the MITT population. The frequency of adverse events and drug-related adverse events were similar between treatment groups. The most common adverse events reported in both treatment groups were headache, nausea, constipation, diarrhea, anemia, pain, and pruritus.
Of note were the clinical responses by subgroup. Among CE patients 65 years of age and over, 81 percent of patients treated with MERREM had a satisfactory clinical response at follow-up, compared with 72 percent of patients treated with imipenem-cilastatin. Similarly, in the CE population, among those with diabetes mellitus, 86 percent of patients treated with MERREM had a satisfactory clinical response at follow-up, compared with 72 percent of patients treated with imipenem-cilastatin. Among patients with microbiologically-documented infection, MERREM demonstrated an excellent success rate in patients infected with Gram-positive aerobes (88 percent versus 83 percent), Gram-negative aerobes (80 percent versus 75 percent), and anaerobic pathogens (84 percent versus 85 percent; MERREM versus imipenem-cilastatin).
The pivotal clinical trial was supported by a pharmacokinetic trial
demonstrating that MERREM administered at 500 mg IV every eight hours achieves levels in interstitial skin fluid sufficient to treat the common pathogens
associated with complicated skin infections.
There are approximately 1.5 million patients who annually receive broad-
spectrumantibiotics in hospitals for cSSSI. Complicated skin and skin structure infections involve the skin and may involve deeper soft tissues, often requiring surgical intervention and antibiotic therapy. These infections include complicated cellulitis, complex abscesses, perirectal abscesses, and other skin infections requiring intravenous antimicrobials and hospitalization.