Sodium thiosulfate decreases cisplatin-associated hearing loss in pediatric patients
Sodium thiosulfate (Pedmark, Fennec Pharmaceuticals Inc.) has been approved by the FDA as treatment to help decrease the risk of cisplatin-related ototoxicity in pediatric patients aged 1 month or older who have received a diagnosis of localized, non-metastatic solid malignancies.
The compound, with or without cisplatin, was evaluated as part of the phase 3 SIOPEL6 trial (NCT00652132) in pediatric patients with stage I to III childhood liver cancer as well as in the phase 3 COG ACCL0431 study (NCT00716976) in pediatric patients with newly diagnosed germ cell tumors, hepatoblastoma, medulloblastoma, neuroblastoma, osteosarcoma, or another malignancy who were being treated with cisplatin.
The incidence of hearing loss in the SIOPEL trial among patients who received sodium thiosulfate was 39% compared with 68% in patients who received cisplatin alone (HR, 0.58; 95% CI, 0.40-0.83). In the COG ACCL0431 trial, 44% of patients experienced hearing loss in the sodium thiosulfate and cisplatin arm vs 58% in the cisplatin alone arm (HR, 0.75; 95% CI, 0.48-1.18). In total, 114 patients with standard-risk hepatoblastoma who underwent 6 cycles of treatment with cisplatin were included in the SIOPEL6 trial. Patients were randomly assigned 1:1 to receive cisplatin-based chemotherapy with or without sodium thiosulfate at different dosing levels, including 10 g/m2, 15 g/m2, and 20 g/m2.
The COG ACCL0431 included 125 patients with solid malignancies who were treated with 200 mg/m2 of cisplatin or more. A total of 77 patients were included in the efficacy analysis.
EUA for monkeypox vaccine changes administration/dosing
The FDA granted emergency use authorization (EUA) to Bavarian Nordic's Jynneos (smallpox and monkeypox vaccine, live, nonreplicating) to allow vaccine administration via intradermal injection for adults 18 years of age and older who are determined to be at high risk for monkeypox infection. Monkeypox was declared a public health emergency on August 4, 2022. The current supply of monkeypox vaccine is not adequate to meet the current demand, according to the Biden administration. The EUA allowing the change to intradermal administration of Jynneos from the originally approved subcutaneous method of administration is intended to significantly increase the availability of the vaccine because intradermal administration allows the number of available doses of monkeypox vaccine to be five times the number that would be available if the vaccine were given only via subcutaneous injection.
Jynneos was approved in 2019 to prevent smallpox and monkeypox disease in adults at high risk for smallpox or monkeypox infection. Using the intradermal route of Jynneos still requires that two doses of Jynneos be given 4 weeks apart, as is required for subcutaneous administration. The EUA also allows the monkeypox vaccine to be administered to individuals under 18 years of age who are determined to be at high risk of monkeypox infection. For individuals under 18 years of age, Jynneos should be administered by subcutaneous injection.
Rapid-acting oral antidepressant Auvelity approved
The FDA approved Auvelity (dextromethorphan HBr and bupropion HCl) extended-release tablets 45 mg/105 mg, for major depressive disorder (MDD) in adults. It is the first and only rapid-acting oral antidepressant labeled to start working at 1 week. It is the first oral N-methyl D-aspartate receptor antagonist for the treatment of MDD in adults. The FDA designated Auvelity a Breakthrough Therapy.
In clinical trials the rapid antidepressant effects of Auvelity were sustained at all subsequent time points in studies, and Auvelity was statistically significantly superior to bupropion sustained-release tablets 105 mg twice daily on the primary outcome measure.
In clinical trials, the most common adverse reactions were dizziness, headache, diarrhea, somnolence, dry mouth, sexual dysfunction, and hyperhidrosis. Auvelity is a product of Axsome Therapeutics.