Efficacy of rimegepant for the acute treatment of migraine based on triptan treatment experience: Pooled results from three phase 3 randomized clinical trials.

BACKGROUND: This post-hoc analysis from three phase 3 treatment trials of rimegepant 75 mg - an oral small molecule calcitonin gene-related peptide receptor antagonist for acute and preventive treatment of migraine - assessed efficacy in adults with migraine based on triptan treatment experience. METHODS: Participants were assigned to one of four groups based on triptan treatment experience: insufficient response (e.g. lack of efficacy and/or poor tolerability) to 1 triptan, insufficient response to ≥2 triptans, current triptan users, and triptan-naïve participants. The co-primary efficacy endpoints were pain freedom and most bothersome symptom freedom at two hours postdose. RESULTS: In the three trials (N = 3507; rimegepant n = 1749, placebo n = 1758), 1235 (35.2%) participants had a history of insufficient response to 1 triptan (n = 910 [25.9%]) or ≥2 triptans (n = 325 [9.3%]), and 2272 (64.8%) had no history of insufficient response to triptans (current use = 595 [17.0%], naïve = 1677 [47.8%]). Rimegepant was effective on the co-primary endpoints in all subgroups (p ≤ 0.013), except for freedom from the most bothersome symptom in the triptan-naïve group (p = 0.06). No differences on co-primary endpoints were found in pairwise comparisons of rimegepant-treated participants. CONCLUSIONS: Rimegepant was effective for the acute treatment of migraine in adults with a history of insufficient response to 1 or ≥2 triptans and in current triptan users. Efficacy on co-primary endpoints did not differ based on the number of insufficient triptan responses.Trial registration: Clinicaltrials.gov: NCT03235479, NCT03237845, NCT03461757.

Ledipasvir-Sofosbuvir: A Once-Daily Oral Treatment Option for Chronic Hepatitis C Virus Genotype 1 Infection.

Chronic hepatitis C virus (HCV) genotype 1 historically has been the most difficult to treat HCV genotype, and patients infected with this genotype had been previously treated with interferon-based therapy. In recent years, however, treatment options for chronic HCV infection have rapidly changed to an all-oral regimen. Ledipasvir-sofosbuvir is an oral fixed-dose (ledipasvir 90 mg-sofosbuvir 400 mg) combination of two direct-acting antiviral drugs. Four phase 3 clinical trials (ION-1-4) evaluated ledipasvir-sofosbuvir with and without ribavirin in patients with HCV genotype 1. High rates of sustained virologic response (SVR) occurred with ledipasvir-sofosbuvir alone in treatment-naïve and treatment-experienced patients without cirrhosis as well as in treatment-naïve patients with cirrhosis when administered for 12 weeks. In treatment-experienced patients with cirrhosis, 24 weeks of ledipasvir-sofosbuvir was also highly effective. Furthermore, treatment-naïve patients without cirrhosis (particularly those with HCV RNA serum concentrations < 6 million IU/ml) can achieve a similar SVR with only 8 weeks of therapy. Similarly, in patients coinfected with human immunodeficiency virus and HCV genotype 1 who were treated with ledipasvir-sofosbuvir for 12 weeks, a high SVR was observed in those with and without cirrhosis as well as treatment-naïve and treatment-experienced patients. Ledipasvir-sofosbuvir is well tolerated, with fatigue, headache, nausea, diarrhea, and insomnia being the most common adverse effects, which are typically mild to moderate in nature. This combination antiviral can be taken with or without food. Key factors to consider when prescribing ledipasvir-sofosbuvir are drug interactions including those mediated by the P-glycoprotein transporter and increased pH, cost of the drug or insurance coverage, comorbid conditions, and patient and provider preferences. Postmarketing experience and ongoing clinical trials will further define the safety and role of ledipasvir-sofosbuvir in the treatment of HCV genotype 1.