Congenital disorders
Latest 2023 FDA Approvals
Aug
The US Food and Drug Administration (FDA) recently approved drugs relevant to conditions often treated by nurse practitioners and PAs. Approvals include treatments for respiratory syncytial virus (RSV) in infants, postpartum depression, colorectal cancer, iron deficiency, and pediatric constipation.
BeyfortusTM for RSV in Infants and Toddlers
BeyfortusTM (nirsevimab-alip), a monoclonal antibody, has been approved by the FDA for the prevention of RSV lower respiratory tract disease in infants born during their first RSV season and children up to 2 years who remain vulnerable to RSV.
Approval was based on data from the Beyfortus clinical development program, which included a phase 2b trial, the phase 3 MELODY trial, and the phase 2/3 MEDLEY trial. In the phase 2b trial, infants born during or entering their first RSV season were randomly assigned to receive a single dose of Beyfortus (n=969) or placebo (n=484). Results indicated that infants receiving Beyfortus significantly reduced the incidence of RSV by 70.1% (95% CI, 52.3-81.2; P <.001). There were 25 cases reported in the Beyfortus group and 46 cases reported in the placebo group.
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Findings from the MELODY trial showed that treatment with nirsevimab was associated with statistically significant reduction in the incidence of medically-attended RSV-associated lower respiratory tract infection (LRTI) and a lower incidence of hospitalization for RSV-associated LRTI compared with placebo.
In the MEDLEY trial, the safety and tolerability of Beyfortus was compared with Synagis (palivizumab), a monoclonal antibody approved to prevent serious lung disease caused by RSV in infantsl, in approximately 925 infants with congenital heart disease, chronic lung disease, and/or prematurity before entering their first RSV season. Results showed that Beyfortus had a similar safety profile compared with Synagis.
Most common adverse reactions include rash and injection site reactions. There is a risk for serious hypersensitivity reactions, including anaphylaxis, and clinicians should exercise caution when administering to children with bleeding disorders.
Beyfortus is supplied as a 50 mg/0.5 mL and 100 mg/mL prefilled syringe and is expected to be available for the upcoming 2023-2024 RSV season.
ZurzuvaeTM for Postpartum Depression
The FDA approved ZurzuvaeTM (zuranolone), a neuroactive steroid gamma-aminobutyric acid (GABA)-A receptor positive allosteric modulator, for the oral treatment of postpartum depression. The agent is taken orally in the evening for 2 weeks.
Approval was based on data obtained from the NEST program that included 2 randomized, placebo-controlled, double-blind studies that evaluated Zurzuvae in adult women diagnosed with postpartum depression, (SKYLARK and ROBIN).
In SKYLARK, patients received Zurzuvae 50 mg (n=98) or placebo (n=97). In ROBIN, patients received another zuranolone capsule approximately equivalent to 40 mg of Zurzuvae (n=76) or placebo (n=74). Treatment was administered once daily in the evening with food for 14 days. Patients were followed for a minimum of 4 weeks.
The study founde that treatment with Zurzuvae led to a statistically significant improvement in depressive symptoms compared with placebo as measured by HAMD-17 total score. The placebo-subtracted difference was -4.0 (95% CI, -6.3, -1.7) in SKYLARK and -4.2 (95% CI, -6.9, -1.5) in ROBIN.
The most common adverse reactions reported include somnolence, dizziness, diarrhea, fatigue, nasopharyngitis, and urinary tract infection. Zurzuvae is supplied in 20 mg, 25 mg, and 30 mg capsules. The treatment should be administered with a fat-containing meal.
Lonsurf® Plus Bevacizumab for Colorectal Cancer
Lonsurf® (trifluridine/tipiracil) in combination with bevacizumab has been approved for treatment of drug-resistant metastatic colorectal cancer. Lonsurf is taken with bevacizumab for the treatment of adults who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy; an anti-VEGF biological therapy; and if the tumor is RAS wild-type. Lonsurf was previously approved as a sing agent therapy for patients with metastatic colorectal cancer.
Approval was based on data from the phase 3 SUNLIGHT trial that compared the safety and efficacy of Lonsurf with bevacizumab (n=246) to Lonsurf as a single agent (n=246) in adults who had a maximum of 2 prior chemotherapy regimens and demonstrated progressive disease or intolerance to the last regimen.
The primary endpoint was overall survival (OS). Median OS was reported to be 10.8 months in the Lonsurf plus bevacizumab arm compared with 7.5 months in the Lonsurf monotherapy arm (hazard ratio [HR], 0.61; 95% CI, 0.49-0.77; 1-sided P <.001).
Injectafer® for Iron Deficiency in Adults with Heat Failure
Injectafer® (ferric carboxymaltose injection) was approved by the FDA for the treatment of iron deficiency in adult patients diagnosed with heart failure.
Approval was based on data obtained from the randomized, double-blind, placebo-controlled phase 4 CONFIRM-HF trial that evaluated the safety and efficacy of Injectafer in adult patients with iron deficiency and chronic heart failure. Patients were randomly assigned to receive either a single dose of Injectafer or placebo on day 0. The primary endpoint was the change from baseline to week 24 in 6-minute walk distance (6MWD).
The mean change in 6MWD from baseline to week 24 in Injectafer-treated patients was reported to be 18 meters (95% CI, 4-32) compared with -7 meters (95% CI, -21-7) in the placebo group (treatment difference, 25 meters; [95% CI, 7-43]; P =.007).
The most common adverse reactions reported were headache, nausea, hypertension, injection site reactions, hypophosphatemia, and dizziness.
Linzess® for Pediatric Functional Constipation
The FDA has approved Linzess® (linaclotide) for the treatment of functional constipation in pediatric patients aged 6 to 17 years.
The approval was based on data from a phase 3 trial that evaluated the safety and efficacy of Linzess in 328 patients with functional constipation. Patients were randomly assigned 1:1 to receive linaclotide 72 mcg or placebo once daily for 12 weeks.
Results showed that patients in the linaclotide group had significant improvements in spontaneous bowel movement frequency compared with placebo (least squares 12-week mean change from baseline in SBM frequency rate: 2.6 vs 1.3, respectively; P <.0001). Bowel movement frequency in the treatment group improved during week 1 and was maintained throughout the remainder of the 12-week treatment period.
The most common adverse reaction reported was diarrhea. Linaclotide carries a Boxed Warning concerning the risk of serious dehydration in patients less than 2 years of age and is contraindicated for this group. The recommended dosage is 72 mcg orally once daily.
References
1. Beyfortus. Prescribing information. Sanofi; 2023. Accessed August 21, 2023. https://products.sanofi.us/beyfortus/beyfortus.pdf
2. Zurzuvae. Prescribing information. Biogen; 2023. Accessed August 21, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217369s000lbl.pdf
3. Lonsurf. Prescribing information. Taiho Oncology; 2023. Accessed August 21, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/207981s012lbl.pdf.
4. Inhectafer. Prescribing informayion. American Regent, Inc.; 2023. Accessed August 21, 2023. https://daiichisankyo.us/prescribing-information-portlet/getDocument?product=IF&inline=true.
5. Linzess. Prescribing information. AbbVie and Ironwood Pharmaceuticals. Accessed August 21, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/202811s021lbl.pdf.
