Trofinetide in Rett syndrome: A brief review of safety and efficacy.

Rett syndrome (RTT) is a rare genetic neurological disorder that primarily affects girls and is caused by mainly mutations in the methyl-CpG-binding protein 2 (MECP2) gene, leading to critical issues in normal brain function. The condition has a global prevalence of 5 to 10 cases per 100,000 females, and there is currently no cure for RTT. However, therapy is available to manage the symptoms and improve quality of life. Trofinetide, an insulin-like growth factor 1, was originally developed as a stroke medication and progressed to Phase II clinical trials, where it exhibited favorable safety and efficacy profiles by improving several core RTT symptoms. Recently, Trofinetide received the US Food and Drug Administration (FDA) approval and orphan drug designation for the treatment of RTT, making it the first approved drug for this rare genetic disorder. It has also shown to be safe, well-tolerated and with no known drug interactions. These findings suggest that Trofinetide is a promising treatment option for individuals with RTT.

Viloxazine for Attention-Deficit Hyperactivity Disorder: A Systematic Review and Meta-analysis of Randomized Clinical Trials.

Background: Recently, the United States Food and Drug Administration (USFDA) approved viloxazine extended-release (ER) to manage attention-deficit hyperactivity disorder (ADHD) in pediatric patients of 6-17 years of age. Objective: To perform a meta-analysis to determine the safety and efficacy of viloxazine ER in the management of ADHD. Data Source and Methods: A literature search was performed through the databases Cochrane Library, PubMed, and clinicaltrials.gov, for a period from inception to August 2021, with the keywords: viloxazine, SPN-812, ADHD, and randomized clinical trials. The randomized controlled trials published in English language that analyzed the efficacy and safety were included. The risk of bias (RoB) was assessed by RoB tool. The outcomes included in this study were the proportion of patients with a 50% reduction in ADHD-Rating Scale-5 (ADHD-RS-5 responders) and improvement in CGI-I scale and the proportion of patients with at least one adverse event, the incidence of somnolence and Serious Adverse Events (SAEs). Results: This meta-analysis includes 1605 patients from five randomized clinical trials; all of the trials were at low risk of bias. Viloxazine group had more ADHD-RS-5 responders as compared to placebo; RR = 1.62; 95% CI = 1.36-1.93; P = <.00001. Significantly higher number of patients showed improved CGI-I score; RR = 1.53; 95% CI = 1.32-1.78; P = <.00001. A higher proportion of patients was observed with at least one adverse event (RR = 1.52; 95% CI = 1.24-1.85; P = <.0001), and somnolence (RR = 3.93; 95% CI = 2.11-7.31; P = <.0001) in viloxazine group. The incidence of SAEs was more in viloxazine group (RR = 2.98; 95% CI = .67-13.3; P = .15). Conclusions: Viloxazine was found to be significantly superior to placebo in both efficacy outcomes. Adverse events and somnolence were significantly more than the placebo. The incidence was SAEs was more in the viloxazine group but was not statistically significant.

Atogepant for Migraine Prevention: A Systematic Review of Efficacy and Safety.

BACKGROUND AND OBJECTIVE: Atogepant is the latest calcitonin gene-related peptide (CGRP) antagonist approved exclusively for prophylaxis of episodic migraine and is administered orally in doses of 10-60 mg/day. This article aims to provide a systematic review of the efficacy and safety of atogepant in migraine prevention. METHODS: The literature was searched in different databases, i.e., the National Institute of Health clinical trials registry, PubMed, and the Cochrane library between 2018 to October 2021 using the keywords atogepant, MK-8031, and migraine. Conference abstracts listed in the Cochrane database (includes Embase) and drug information provided by the US Food and Drug Administration (FDA) label were also reviewed. Only English-language clinical trials were included. The authors retrieved 58 articles. Eventually, two randomized, double-blind, multicenter clinical trials involving 1,727 participants and one open-label trial were analyzed. RESULTS: The FDA approved atogepant for migraine prevention in September 2021 based on two randomized, double-blind, placebo-controlled trials. Atogepant approved for migraine prevention acts as a CGRP receptor antagonist and is administered orally. Based on the 12-week clinical trials, atogepant was efficacious in prevention of migraine and it was well tolerated. The most common treatment-emergent adverse events were nausea, constipation, and upper respiratory infection. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Atogepant had a statistically significant change from baseline in monthly migraine days, monthly headache days, and acute medication use days. CONCLUSIONS: Atogepant seems to be beneficial for migraine prevention, and it may be of more benefit in individuals who do not wish to take the drug as an injection or do not require a prolonged duration of drug effect. However, head-to-head trials with other CGRP antagonists are required to ascertain its place in migraine prevention.