FDA Approvals Roundup: Zynrelef, Empaveli, Ingrezza
A weekly update on new drug approvals and indications from the US Food and Drug Administration (FDA).New indications
Zynrelef cleared as long-acting combination therapy for postoperative pain
Heron’s Zynrelef (bupivacaine and meloxicam) extended-release solution has been approved as a postsurgical analgesic lasting for up to 72 hours in adults who have undergone bunionectomy, open inguinal herniorrhaphy, and total knee arthroplasty. The approval is for use in soft tissue or periarticular instillation; safety and efficacy have not been established in highly vascular surgeries, such as head and neck procedures.
The fixed-dose combination of the liposomal bupivicaine, a long-lasting local anesthetic, and low-dose meloxicam, a nonsteroidal anti-inflammatory drug, has also shown efficacy in reducing patient need for post-surgery opioids.
Zynrelef’s approval was based on findings from three separate Phase 3, multicenter, double-blind, parallel-group, active- and placebo-controlled clinical studies. The 1,052 patients in EPOCH 1, EPOCH 2, and a third study were treated with for pain after bunionectomy, herniorrhaphy, and total knee arthroplasty, respectively. In the EPOCH studies, the active control was the current standard of care, bupivacaine HCL solution; and in the third study, it was Zynrelef plus ropivacaine. All three studies had a saline placebo group.
Patients rated pain intensity on the 11-point numeric rating scale 72 hours out from treatment. Findings from all three studies demonstrated a significant reduction in pain intensity among patients treated with Zynrelef compared with those who received bupivacaine HCL solution alone or placebo. There was also a significant reduction in total opioid consumption over the 72-hour period.
Empaveli approved as new treatment for adults with serious rare blood disease
Apellis’ Empaveli (pegcetacoplan injection) has been approved for use in adults with paroxysmal nocturnal hemoglobinuria (PNH), a rare, life-threatening blood disease.
PNH is caused by gene mutations in bone marrow stem cells that cause hemolysis, which can result in hemolytic anemia, blood clots, and impaired bone marrow function.
Empaveli’s approval was based on efficacy and safety findings in a Phase 3, randomized, multicenter, active-comparator controlled study with 80 patients from the indicated population who were previously treated with eculizumab. They received twice weekly Empaveli for 4 weeks concurrent with their previous dosage of eculizumab before being randomized to receive Empaveli or eculizumab alone for 16 weeks. Average baseline hemoglobin concentration for both groups was 8.7 g/dL, an indication of severe anemia. After 16 weeks, average hemoglobin levels increased by 2.4 g/dL in the study group, compared with an average decrease of 1.5 g/dL in the eculizumab group.
Empaveli is available only through a restricted program under a risk evaluation and mitigation strategy.
New indications
New-dose Ingrezza okayed for treating tardive dyskinesia
Neurocrine Biosciences’ Ingrezza (valbenazine capsules) has received approval for a new 60-mg dosing option for treating tardive dyskinesia.
Ingrezza was originally approved in 2017 in 40- and 80-mg capsule form for treating adults with tardive dyskinesia. Efficacy of the 60-mg dose was demonstrated through modeling and clinical trial simulations. The development program for the supplemental new drug application was facilitated by the FDA’s Model-Informed Drug Development (MIDD) paired meeting pilot program. The findings suggested the predicted mean change from baseline in the Abnormal Involuntary Movement Scale dyskinesia total score after 6 weeks for the 60 mg dose would be -2.69 (95% confidence interval, -3.30 to -2.13), within the efficacy range for the 40- and 80-mg doses.
Levothyroxine sodium injection approved for treating hypothyroidism complication
Custopharm’s levothyroxine sodium injection has been approved for treating myxedema coma, a complication of severe hypothyroidism manifested by a range of symptoms, including confusion or mental slowness, decreased breathing, low blood oxygen levels and high blood carbon dioxide levels, and seizures.
According to the prescribing information, the therapy has not been studied in patients with myxedema coma. The current approval was based on data from published literature supporting intravenous use of levothyroxine sodium for treating the condition.
Injectafer okayed as single-dose option for iron deficiency anemia in adults
American Regent’s Injectafer (ferric carboxymaltose injection) has received approval for a new maximum 1,000-mg, single-dose regimen for treating iron deficiency anemia (IDA) in adults with oral iron intolerance or nondialysis-dependent chronic kidney disease or who have not had adequate response to previous oral iron treatment.
The iron replacement product was originally approved in 2013 as a two-dose regimen totaling 1,500 mg, administered with at least 7 days between the first and second doses. Each dose is to a maximum of 750 mg.
The safety and efficacy of Injectafer was demonstrated in findings from two randomized, open-label, controlled studies IDA and REPAIR-IDA using the 1,500-mg dose. The treatment’s safety and tolerability were also evaluated in two additional trials using the maximum 1,000-mg single dose.