The US Food and Drug Administration (FDA) approved drugs in March relevant to conditions often treated by nurse practitioners and PAs. Approvals include treatments for candidemia and invasive candidiasis, obstructive sleep apnea for pediatric patients with Down syndrome, pediatric BRAF V600E low-grade glioma, and migraines.
RezzayoTM for Candidemia and Invasive Candidiasis
The FDA approved the once-weekly echinocandin antifungal RezzayoTM (rezafungin for injection) for the treatment of candidemia and invasive candidiasis in adults with limited or no treatment options. Approval was based on data from the randomized, double-blind phase 3 ReSTORE study (ClinicalTrials.gov Identifier: NCT03667690) that included 187 adults diagnosed with candidemia and/or invasive candidiasis.
Razzayo was noninferior to caspofungin for the primary endpoint of all-cause mortality at day 30, using a 20% noninferiority margin. The trial provided evidence for efficacy to support an indication with a limited use statement, given the wider noninferiority margin. All-cause mortality at day 30 was 23.7% in the rezafungin group and 21.3% in the caspofungin group (treatment difference, 2.4% [95% CI, -9.7, 14.4]).
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Approval was also supported by safety and efficacy data obtained from double-blind, randomized, phase 2 STRIVE study (ClinicalTrials.gov Identifier: NCT02734862).
The most common adverse reactions reported were hypokalemia, pyrexia, diarrhea, anemia, vomiting, nausea, hypomagnesemia, abdominal pain, constipation, and hypophosphatemia.
Rezzayo is supplied as a solid (cake or powder) in a single-dose vial containing 200 mg of rezafungin. Treatment is administered once weekly by intravenous infusion after reconstitution.
Inspire Therapy for OSA in Pediatric Patients With Down Syndrome
The FDA expanded approval of Inspire therapy to include pediatric patients 13 years and older with Down syndrome who have obstructive sleep apnea (OSA) with an apnea-hypopnea index between 10 and 50 and who are unable to benefit from continuous positive airway pressure.
Inspire therapy is a fully implanted neurostimulation device that consists of a small generator, sensing lead, and stimulation lead and is placed under the skin of the neck and chest. The device senses breathing patterns and mildly stimulates key airway muscles to keep the airway open during sleep.
Approval was based on a clinical trial that included 42 patients with Down syndrome and persistent severe OSA (ClinicalTrials.gov Identifier: NCT02344108). The upper airway stimulation was safely performed in these patients and resulted in high rates of response and improved quality of life.
Tafinlar® + Mekinist® for Pediatric BRAF V600E Low-Grade Glioma
Tafinlar® (dabrafenib) with Mekinist® (trametinib) was approved by the FDA for the treatment of pediatric patients 1 year and older with low-grade glioma with a BRAF V600E mutation who require systemic therapy. Previously, the therapy was only approved for adults.
Approval was based on data from the phase 2/3 TADPOLE trial (ClinicalTrials.gov Identifier: NCT02684058) that evaluated the combination in pediatric patients younger than 18 years of age with BRAF V600E mutation-positive low-grade glioma (WHO grades 1 and 2) who required systemic therapy.
Patients were randomly assigned 2:1 to dabrafenib plus trametinib (D+T; n=73) or carboplatin plus vincristine (C+V; n=37). The primary endpoint was overall response rate (ORR); progression-free survival (PFS) and overall survival were additional efficacy outcome measures.
A statistically significant improvement in ORR was found in the D+T group vs the C+V group (46.6% [95% CI, 34.8-58.6] vs 10.8% [95% CI, 3.0-25.4]; P <.001). At a median follow-up of 18.9 months, median PFS was 20.1 months (95% CI, 12.8, not estimable) with D+T and 7.4 months (95% CI, 3.6-11.8) with C+V (hazard ratio, 0.31 [95% CI, 0.17-0.55]; P <.001).
The most common adverse reactions included pyrexia, rash, headache, vomiting, musculoskeletal pain, fatigue, diarrhea, dry skin, nausea, hemorrhage, abdominal pain, and dermatitis acneiform. Grade 3 or 4 laboratory abnormalities included decreased neutrophil count, increased alanine aminotransferase, and increased aspartate aminotransferase.
Zavzpret™ Nasal Spray for Migraine
The FDA approved Zavzpret™ (zavegepant) nasal spray, a calcitonin gene-related peptide (CGRP) receptor antagonist, for the acute treatment of migraine with or without aura in adults.
Approval was based on data from 2 double-blind, placebo-controlled studies (ClinicalTrials.gov Identifier: NCT04571060, NCT03872453) that evaluated the safety and efficacy of zavegepant in adult patients with at least a 1-year history of migraines.
Results indicated that treatment with a single intranasal dose of zavegepant was statistically superior to placebo on the coprimary endpoints of pain freedom and freedom from the most bothersome symptom (nausea, photophobia, phonophobia) at 2 hours.
Zavegepant was superior to placebo for additional endpoints of pain relief at 2 hours post-dose, return to normal function at 2 hours post-dose, sustained pain freedom from 2 to 48 hours post-dose, and phonophobia and photophobia freedom at 2 hours post-dose.
Common adverse reactions reported by patients treated with zavegepant were taste disorders, nausea, nasal discomfort, and vomiting.
Zavzpret™ is supplied as a carton of 6 units with a ready-to-use, unit-dose disposable device with each unit containing 10 mg.
References
1. Rezzayo. Prescribing information. Cidara Therapeutics and Melinta Therapeutics; 2023. Accessed March 31, 2023. https://rezzayo.com/pdfs/REZZAYO%20(rezafungin%20for%20injection)%20Package%20Insert.pdf
2. Inspire Medical Systems, Inc. announces FDA approval for pediatric patients with Down syndrome. News release. Inspire Medical Systems, Inc. Accessed March 21, 2023. https://www.globenewswire.com/news-release/2023/03/21/2631228/0/en/Inspire-Medical-Systems-Inc-Announces-FDA-Approval-for-Pediatric-Patients-with-Down-Syndrome.html
3. Tafinlar. Prescribing information. Novartis; 2023. Accessed March 31, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/202806s025lbl.pdf
4. Mekinist. Prescribing information. Novartis; 2023. Accessed March 31, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/204114s025lbl.pdf
5. Zavzpret. Prescribing information. Pfizer Inc; 2023. Accessed March 31, 2023. https://labeling.pfizer.com/ShowLabeling.aspx?id=19471
